amphotericin-b and Candidiasis

Systemic candidiasis is caused by Candida invading the bloodstream. The efficacy and safety of echinocandins in monotherapy and combination therapy regimes have not been adequately compared in immunocompromised patients with Candidiasis, and thus this systematic review aims to do so.. A protocol was prepared a priori. PubMed, Embase and Cochrane Library databases were searched systematically (from inception of each database to September 2022) to identify randomized controlled trials. Two reviewers performed screening, quality assessment of trials, and extracted data independently. Pairwise meta-analysis was performed using random-effects model to compare echinocandin monotherapy versus other antifungals. The primary outcomes of interest were treatment success and treatment-related adverse events.. 547 records (PubMed=310, EMBASE=210 and Cochrane Library=27) were reviewed. Following our screening criteria, six trials involving 177 patients were included. Risk of bias of four included studies had some concerns due to lack of a pre-specified analysis plan. Meta-analysis shows that echinocandin monotherapy does not have significantly higher rates of "treatment success" compared to other classes of antifungals (RR 1.12, 95%CI 0.80-1.56). However, echinocandins appeared to be significantly safer than other forms of antifungal therapy (RR 0.79, 95%CI 0.73-0.86).. Our findings have shown that echinocandin monotherapy (micafungin, caspofungin) given intravenously are just as effective as other antifungals (amphotericin B, itraconazole) in the treatment of systemic candidiasis in immunocompromised patients. There appears to be similar benefits when using echinocandins compared to amphotericin B which has also been used as a broad-spectrum antifungal, while avoiding the severe adverse effects that amphotericin B causes, such as nephrotoxicity.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Echinocandins; Humans; Immunocompromised Host; Lipopeptides

Invasive Candida infections threaten human health due to the increasing incidence of resistance to the currently available antifungal agents. Amphotericin B (AMB) is the gold standard therapy to treat these infections. Nevertheless, the use of such substance in the clinic is aggravated by its toxicity. Since AMB binds to membrane sterols, it forms pores on human plasma membranes, mainly in kidney cells, leading to nephrotoxicity. The combination of this drug to a second substance could allow for the use of smaller concentrations of AMB, consequently lowering the probability of adverse effects. This mini-review summarizes information regarding an array of substances that enhance AMB antifungal activity. It may be noticed that several of these compounds target plasma membrane. Interestingly, substances approved for human use also presented combinatory anti-Candida activity with AMB. These data reinforce the potential of associating AMB to another drug as a promising therapeutical alternative to treat Candida infections. Further studies, regarding mechanism of action, pharmacokinetics and toxicity parameters must be conducted to confirm the role of these substances as adjuvant agents in candidiasis therapy.

Topics: Adjuvants, Immunologic; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug-Related Side Effects and Adverse Reactions; Humans

Antifungal resistance to

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidiasis; Echinocandins; Fluconazole; Humans; Microbial Sensitivity Tests

BACKGROUND + OBJECTIVES: The echinocandins, amphotericin B preparations, voriconazole and fluconazole are approved for the treatment of invasive candidiasis, though it remains unclear which agent is most effective. In order to answer this question, we performed a systematic review and network meta-analysis of the randomised controlled trials (RCTs) which evaluated these agents in comparison.. Four electronic databases were searched from database inception to 8 October 2020. RCTs comparing triazoles, echinocandins or amphotericin B for the treatment of invasive candidiasis or candidemia were included. Random effect Bayesian network meta-analysis methods were used to compare treatment outcomes.. Thirteen RCTs met inclusion criteria. Of the 3528 patients included from these trials, 1531 were randomised to receive an echinocandin, 944 to amphotericin B and 1053 to a triazole. For all forms of invasive candidiasis, echinocandins were associated with the highest rate of treatment success when compared to amphotericin B (OR 1.41, 95% CI 1.04-1.92) and the triazoles (OR 1.82, 95% CI 1.35-2.51). Rank probability analysis favoured echinocandins as the most effective choice 98% of the time. Overall survival did not significantly differ between groups.. Among patients with invasive candidiasis, echinocandins had the best clinical outcomes and should remain the first-line agents in the treatment of invasive candidiasis.

Topics: Amphotericin B; Antifungal Agents; Candidemia; Candidiasis; Candidiasis, Invasive; Echinocandins; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Triazoles

To describe a case of thrombophlebitis associated with Candida infection and to analyze other published reports to define clinical characteristics, prognostic data, diagnostic and therapeutic strategies.. A computerized search was performed without language restriction using PubMed and Scopus databases. An article was considered eligible for inclusion if it reported cases with Candida thrombophlebitis. Our case was also included in the analysis.. A total of 16 articles reporting 27 cases of Candida thrombophlebitis were included in our review. The median age of patients was 4 years. In 10 cases there was a thrombophlebitis of peripheral veins; in the remaining cases the deep venous circle was interested. Candida albicans was the most frequently involved fungal species. The most recurrent risk factors were central venous catheter (19/28), broad spectrum antibiotics (17/28), intensive care unit (8/28), surgery (3/28), mechanical assisted ventilation (5/28), total parenteral nutrition (8/28), cancer (2/28), premature birth (6/28), cystic fibrosis (2/28). Fever was the most frequent clinical feature. All children with peripheral and deep thrombophlebitis were given antifungal therapy: amphotericin B was the most used, alone or in combination with other antifungal drugs. Heparin was most frequently used as anticoagulant therapy. Illness was fatal in two cases.. Candida thrombophlebitis is a rare but likely underdiagnosed infectious complication in pediatric critically ill patients. It is closely connected to risk factors such as central venous catheter, hospitalization in intensive care unit, prematurity, assisted ventilation, chronic inflammatory diseases. Antifungal therapy and anticoagulant drugs should be optimized for each patient and surgical resection is considered in the persistence of illness.

Topics: Amphotericin B; Anticoagulants; Antifungal Agents; Candidiasis; Child; Child, Preschool; Cross Infection; Humans; Prognosis; Risk Factors; Thrombophlebitis

Candida auris is a new pathogen called "superbug fungus" which caused panic worldwide. There are no large-scale epidemiology studies by now, therefore a systematic review and meta-analysis was undertaken to determine the epidemic situation, drug resistance patterns and mortality of C. auris.. We systematically searched studies on the clinical report of Candida auris in Pubmed, Embase and Cochrane databases until October 6, 2019. A standardized form was used for data collection, and then statics was performed with STATA11.0.. It showed that more than 4733 cases of C. auris were reported in over 33 countries, with more cases in South Africa, United States of America, India, Spain, United Kingdom, South Korea, Colombia and Pakistan. C. auirs exhibited a decrease in case count after 2016. Clade I and III were the most prevalent clades with more cases reported and wider geographical distribution. Blood stream infection was observed in 32% of the cases, which varied depending on the clades. Resistance to fluconazole, amphotericin B, caspofungin, micafungin and anidulafungin in C. auris were 91, 12, 12.1, 0.8 and 1.1%. The overall mortality of C. auris infection was 39%. Furthermore, subgroup analyses showed that mortality was higher in bloodstream infections (45%), and lower in Europe (20%).. Over 4000 cases of C. auris were reported in at least 33 countries, which showed high resistance to fluconazole, moderate resistance to amphotericin B and caspofungin, high sensitivity to micafungin and anidulafungin. The crude mortality for BSI of C. auris was 45% which was similar to some drug-resistant bacteria previously reported. In conclusion, C. auris displayed similar characteristics to some drug resistance organisms. This study depicts several issues of C. auris that are most concerned, and is of great significance for the clinical management.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Candida; Candidiasis; Caspofungin; Drug Resistance, Multiple, Fungal; Fluconazole; Humans; Micafungin; Prevalence

Identification of the emerging yeast species Candida nivariensis among presumptively identified Iranian Candida glabrata isolates.. Clinical C. glabrata species complex isolates from blood (n=71; 33.3 %), urine (n=100; 46.9 %), vaginal swabs (n=20;9.4 %), BAL (n=10; 4.7 %), and sputum (n=12; 5.6 %) from Iran were investigated. Isolates were characterized by CHROMagar, multiplex PCRs, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), amplified fragment length polymorphism (AFLP) fingerprinting, internal transcribed spacer (ITS)/large subunit (LSU) rDNA and FKS1/FKS2 sequencing, and the European Committee on Antimicrobial Susceptibility Testing broth microdilution method. A comprehensive literature review was conducted and all the relevant clinical and microbiological data were collected.. Four C. nivariensis isolates were recovered from blood samples of three subjects and were all consistently identified by nine-plex PCR, Bruker MALDI-TOF MS, and LSU and ITS rDNA sequencing. AFLP genotyping clustered the isolates into two groups. Sequencing of the FKS1 and FKS2 hotspots showed no accountable amino acid substitutions. All isolates were susceptible to amphotericin B, fluconazole, itraconazole, posaconazole, voriconazole, anidulafungin and micafungin.. In total, 4 out of 213 clinical C. glabrata species complex candidemia isolates were C. nivariensis. Improvement of the BioMerieux Vitek MS database is required to accurately identify C. nivariensis and it is advised to alternatively use CHROMagar and/or PCR-based techniques. As other species within the Nakaseomyces clade may cause infection and showed high MIC values for antifungals, inclusion of their spectra into the MALDI-TOF MS database seems relevant. Due to developing resistance to fluconazole and insufficient efficacy of caspofungin, the combination of catheter removal plus treatment with caspofungin, or voriconazole, or micafungin might be effective for patients.

Topics: Adolescent; Aged; Amphotericin B; Amplified Fragment Length Polymorphism Analysis; Antifungal Agents; Bronchoalveolar Lavage; Candida; Candidemia; Candidiasis; Caspofungin; DNA, Intergenic; Fatal Outcome; Female; Fluconazole; Genotype; Humans; Iran; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Vagina; Voriconazole

Candida auris is an emerging species of yeast characterized by colonization of skin, persistence in the healthcare environment, and antifungal resistance. C. auris was first described in 2009 from a single isolate but has since been reported in more than 25 countries worldwide. Resistance to fluconazole and amphotericin B is common, and resistance to the echinocandins is emerging in some countries. Antifungal resistance has been shown to be acquired rather than intrinsic and the primary mechanisms of resistance to the echinocandins and azoles have been determined. There are a number of new antifungal agents in phase 2 and phase 3 clinical trials and many have activity against C. auris. This review will discuss what is currently known about antifungal resistance in C. auris, limitations to antifungal susceptibility testing, the mechanisms of resistance, and the new antifungals that are on the horizon.

Topics: 14-alpha Demethylase Inhibitors; Aminopyridines; Amphotericin B; Antifungal Agents; Azoles; Candida; Candidiasis; Drug Resistance, Multiple, Fungal; Echinocandins; Fluconazole; Humans; Isoxazoles; Microbial Sensitivity Tests; Pyridines; Tetrazoles

This drug utilization evaluation aims to review current evidence on safety and efficacy of using liposomal amphotericin B (LAMB) in newborns with candidiasis, and compare it to the conventional preparation. Conventional amphotericin B deoxycholate (DAMB) is more commonly used in newborns, but dose-limiting adverse effects may compromise its efficacy. This review will examine the advantages and disadvantages of liposomal amphotericin B and define its place in current practice.. The terms 'AmBisome' or 'liposomal amphotericin B' and 'neonatal candidiasis' were entered in both PubMed and Ovid; studies included focused on safety and efficacy of liposomal amphotericin B in newborns with candidiasis, as well as studies comparing the conventional and the liposomal formulations in newborns as monotherapy. Pertinent references obtained from this search were also included. Additionally, pharmacokinetic studies were reviewed to include available data on dosing. Single case reports were not included in the review due to the limited conclusions that can be drawn from such sample sizes and quality of data.. Although liposomal amphotericin B may be better tolerated and as efficacious as the conventional formulation based on the published literature, the weakness of the studies available on the subject cannot be overlooked. Additional randomized controlled trials are needed to determine the true benefits of this medication.

Topics: Amphotericin B; Candidiasis; Deoxycholic Acid; Drug Combinations; Drug Utilization Review; Humans; Infant, Newborn

Candida species, including Candida dubliniensis, are a rare cause of meningitis. Herein, we report the second case of C. dubliniensis meningitis in a 49-year-old man with a history of hepatitis C virus-related cirrhosis, substance use disorder, and recent exposure to intravenous antibiotic therapy, presenting with confusion, abnormal gait, and urinary incontinence. Magnetic resonance imaging (MRI) of the brain showed marked hydrocephalus and leptomeningeal enhancement. Initial cerebrospinal fluid (CSF) studies were concerning for bacterial meningitis, although cultures were negative. Despite empiric treatment with broad-spectrum antibiotics, the patient's mental status declined. The diagnosis of C. dubliniensis meningitis was not made until the third lumbar puncture. The patient was treated with liposomal amphotericin B and flucytosine. Despite improvement of hydrocephalus on MRI of the brain and sterilization of CSF, the patient's mental status declined and he expired. This case highlights the difficulty in the diagnosis of C. dubliniensis meningitis as multiple lumbar punctures may be necessary. C. dubliniensis meningitis should be considered in the differential diagnosis for a patient with risk factors such as end-stage liver disease, human immunodeficiency virus infection, recent chemotherapy, substance use disorders, and recent broad-spectrum antibiotic use. A high index of suspicion is necessary as delay in initiation of therapy is associated with high mortality. The optimal treatment strategy has not been determined.

Topics: Amphotericin B; Antifungal Agents; Brain; Candida; Candidiasis; Cerebrospinal Fluid; Fatal Outcome; Flucytosine; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Magnetic Resonance Imaging; Male; Meningitis; Middle Aged; Substance-Related Disorders

Walled-off necrosis (WON) caused by fungal infection is very rare, and its treatment is more difficult than that of bacterial infection. We present the first case of a patient with refractory fungal-infected WON treated with percutaneous endoscopic necrosectomy and local administration of amphotericin B.A Japanese man in his 30s was hospitalized with severe necrotizing pancreatitis and multiple organ failure. Computed tomography imaging of the abdomen 1 month after the onset of pancreatitis revealed infected WON. Percutaneous drainage revealed purulent necrotic fluid, and culture of the fluid revealed the presence of Candida albicans and C glabrata. WON was treated by percutaneous endoscopic necrosectomy and local administration of amphotericin B. Consequently, the patient's condition improved, and Candida species were not detected in subsequent cultures.The combination of endoscopic necrosectomy with local administration of amphotericin B may be effective in treating refractory fungal-infected WON.

Topics: Adult; Amphotericin B; Candidiasis; Chronic Disease; Endoscopy, Digestive System; Humans; Male; Necrosis; Pancreatitis, Chronic

Neonatal liver abscess is an uncommon seen condition in neonatology and it holds a very high neonatal mortality because of difficulty in diagnosis and treatment. Till today, only few instances are reported that too are mainly in preterm. Its diagnosis requires a high index of suspicion. Fungal hepatic abscess is very rare and in medical literature very few case reports are there in the medical literature. Here, we report a case of Candida albicans liver abscess in a preterm neonate, secondary to malpositioned umbilical lines that presented with respiratory difficulty and other clinical features of sepsis that was managed medically and discharged successfully.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Catheterization, Central Venous; Fluconazole; Humans; Infant, Newborn; Infant, Premature; Liver Abscess; Male; Treatment Outcome; Umbilical Veins

Candida infection is a relatively common hematogenous nosocomial infection in immunocompromised patients. However, renal disease remains unusual. The mode of presentation in the case reported herein was lumbar pain with fever and hydronephrosis of the left kidney due to a fungal bezoar in the renal pelvis. Clinical and biological suspicion of this disease must quickly lead to ultrasound examination to confirm the diagnosis.

Topics: Amphotericin B; Antifungal Agents; Bezoars; Candidiasis; Child; Diabetes Mellitus, Type 1; Diagnosis, Differential; Female; Flank Pain; Humans; Kidney Pelvis; Opportunistic Infections; Ultrasonography

Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients, although its effect seems to be equivocal.. To study whether nystatin decreases morbidity and mortality when given prophylactically or therapeutically to patients with severe immunodeficiency.. We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.. Randomised clinical trials comparing nystatin with placebo, an untreated control group, fluconazole or amphotericin B.. Data on mortality, invasive fungal infection and colonisation were independently extracted by both authors. A random-effects model was used unless the P value was greater than 0.10 for the test of heterogeneity.. We included 14 trials (1569 patients). The drugs were given prophylactically in 12 trials and as treatment in two. Eleven trials were in acute leukaemia, solid cancer, or bone marrow recipients; one in liver transplant patients; one in critically ill surgical and trauma patients; and one in AIDS patients. Nystatin was compared with placebo in three trials, with fluconazole in 10, and amphotericin B in one; the dose varied from 0.8 MIE to 72 MIE daily and was 2 mg/kg/d in a liposomal formulation. The effect of nystatin was similar to that of placebo on fungal colonisation (relative risk (RR) 0.85, 95% confidence interval (CI) 0.65 to 1.13). There was no statistically significant difference between fluconazole and nystatin on mortality (RR 0.75, 95% CI 0.54 to 1.03) whereas fluconazole was more effective in preventing invasive fungal infection (RR 0.40, 95% CI 0.17 to 0.93) and colonisation (RR 0.50, 95% CI 0.36 to 0.68). There were no proven fungal infections in a small trial that compared amphotericin B with liposomal nystatin. The results were very similar if the three studies that were not performed in cancer patients were excluded. For the 2011 and 2014 updates no additional trials were identified for inclusion.. Nystatin cannot be recommended for prophylaxis or the treatment of Candida infections in immunodepressed patients.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Candidiasis; Fluconazole; Humans; Immunocompromised Host; Liposomes; Mycoses; Nystatin; Opportunistic Infections; Randomized Controlled Trials as Topic

A bibliographic search was conducted of cases of Candida endophthalmitis reported in Japan and overseas between 2000 and 2011, in the Japana Centra Revuo Medicina Website of Japan Medical Abstracts Society (domestic reports) and MEDLINE (overseas reports). The investigation yielded 42 reports in domestic journals (49 cases ; hereinafter referred to as domestic cases) and 39 reports in journals published overseas (46 cases ; hereinafter referred to as overseas cases). The isolation rate of Candida albicans in the domestic cases was 65.3%, and that in the overseas cases was 71.7%. The initial treatment for the Candida endophthalmitis was fluconazole (FLCZ) therapy in 51.0% of the domestic cases and 38.1% of the overseas cases. Domestic reports suggested the effectiveness of FLCZ therapy for stage II cases, and of vitrectomy for stage III and IV cases. Reports from overseas, on the other hand, suggested the effectiveness of amphotericin B (AMPH-B) or voriconazole (VRCZ) therapy for stage II cases, and of vitrectomy for stage III and IV cases.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Endophthalmitis; Female; Fluconazole; Humans; Infant; Japan; Male; MEDLINE; Middle Aged; Pyrimidines; Severity of Illness Index; Time Factors; Treatment Outcome; Triazoles; Vitrectomy; Voriconazole; Young Adult

Despite the relative high frequency of Candida bloodstream infection, Candida endocarditis is a rare entity. We report five cases of Candida endocarditis admitted to our hospital in the period between 2005 and 2011. Two cases were caused by C. albicans, two cases were caused by C. parapsilosis and in the last one, we didn't identify the species of Candida. All but one had clear risk factors for candidemia. Treatment consisted of amphotericin B with / without flucytosine in four patients, and they all underwent surgery for valve replacement and / or removal of intravascular devices. Overall mortality was 60% (40% of mortality was directly related to endocarditis). All patients who survived were given suppressive therapy with fluconazole for a minimum of two years.After stopping fluconazole there was a case of recurrence.

Topics: Acute Kidney Injury; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Candida; Candidiasis; Carcinoma, Transitional Cell; Combined Modality Therapy; Disease Susceptibility; Drug Therapy, Combination; Endocarditis; Fatal Outcome; Female; Fluconazole; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Immunosuppressive Agents; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Pacemaker, Artificial; Postoperative Complications; Pregnancy; Pregnancy Complications, Infectious; Rheumatic Heart Disease; Sjogren's Syndrome; Spain; Tertiary Care Centers; Urinary Bladder Neoplasms

Although therapeutic first-line approaches have been established in severely immunosuppressed patients with a high risk of invasive fungal infections, treatment modalities for cases with unsatisfactory outcome have not been well defined, especially for the pediatric age gap. Therapy with coadministration of two or three antifungals has been applied by clinicians in difficult-to-treat infections, which still have no support from randomized, controlled clinical trials. The most prevailing reason for a combination regimen is to broaden the antimycotic spectrum, which may even result in antagonistic interaction. The experience and recommendations of combinational antifungal therapy for cryptococcal infections, systemic candidiasis, invasive aspergillosis and other rare mold infections have been presented in this review, giving some information on mechanism of action and principles in combined use of mycotic anti-infectives. Most experience of combination therapy approaches are in adult patients; but in fact, there is no conclusive data documenting definite benefits of this approach, either in adults or children.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Candida; Candidiasis; Caspofungin; Child; Cryptococcosis; Cryptococcus; Drug Therapy, Combination; Echinocandins; Humans; Lipopeptides; Pyrimidines; Triazoles; Voriconazole

Cerebral abscess caused by Candida spp. is a rare disease, with a nonspecific presentation, little data on treatment, and generally poor outcomes. We present a case of this type of Candida infection in a 57-year-old man with a history of uncontrolled diabetes mellitus and intravenous drug abuse, and review the literature on this disease. Our patient had a good treatment outcome with liposomal amphotericin B and flucytosine, followed by oral fluconazole. Comorbidities include prior antibiotic use (52%), prior surgery (28%), malignancy (28%), stem cell or solid organ transplant (20%), prior corticosteroid use (16%), central venous catheter (CVC) insertion (10%), and burns (7%). Diagnosis requires a high index of suspicion, as clinical presentations and laboratory data can be nonspecific and difficult to differentiate from bacterial cerebral abscesses. In reviewed cases, 55% of blood cultures and 23% of cerebrospinal fluid (CSF) cultures were positive for Candida spp. and outcomes were poor, as the mortality rate of the non-autopsy cases reviewed was 69%.

Topics: Administration, Intravenous; Administration, Oral; Adolescent; Adult; Amphotericin B; Brain Abscess; Candida; Candidiasis; Child, Preschool; Diabetes Complications; Female; Fluconazole; Flucytosine; Humans; Infant; Male; Middle Aged; Substance Abuse, Intravenous; Young Adult

Candida infections are a source of significant mortality and morbidity in the neonatal intensive care unit. Treatment strategies continue to change as additional antifungals become available and studies in neonates are performed. Amphotericin B deoxycholate has been favored for many years, but fluconazole has the most data supporting its use in neonatal Candida infections and is often employed for prophylaxis as well as treatment. Voriconazole and posaconazole have limited utility in the nursery and are rarely used. The echinocandins are increasingly administered for invasive Candida infections, although higher doses are required in neonates than in older children and adults.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Combinations; Echinocandins; Fluconazole; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intensive Care Units, Neonatal; Neonatology; Pyrimidines; Triazoles; Voriconazole

Candida infections represent challenging causes of severe sepsis and/or of septic shock in the critically ill patients. Knowledge of current pharmacological concepts may promote a more wise use of echinocandins in the management of Candida infections in this setting. Echinocandins have some advantages over azoles, both pharmacodynamically (rapid fungicidal activity, anti-biofilm activity, unmodified activity against Candida isolates with decreased susceptibility to azoles and anti-cytokine/anti-chemokine activity) and pharmacokinetically (low interindividual variability, low potential for drug-drug interactions), that may influence the timing and the choice of therapy of Candida diseases in the critically ill patients. However, concerns exist in regards to the feasibility of fixed dosing regimens of echinocandins in all of the different patient populations and in regards to the effectiveness of echinocandin monotherapy in some clinical settings. In presence of deep-seated infections, voriconazole or liposomal amphotericin B may be valuable alternatives or add-on therapy.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Critical Illness; Drug Administration Schedule; Drug Dosage Calculations; Drug Therapy, Combination; Echinocandins; Humans; Practice Guidelines as Topic; Pyrimidines; Sepsis; Triazoles; Voriconazole

Invasive Candida infections represent a diagnostic and therapeutic challenge for clinicians particularly in the intensive care unit (ICU). Despite substantial advances in antifungal agents and treatment strategies, invasive candidiasis remains associated with a high mortality. Recent guideline recommendations on the management of invasive candidiasis by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) from 2012, the German Speaking Mycological Society and the Paul Ehrlich Society for Chemotherapy (DMykG/PEG) from 2011 and the Infectious Diseases Society of America (IDSA) from 2009 provide valuable guidance for diagnostic procedures and treatment of these infections but need to be interpreted in the light of the individual situation of the patient and the local epidemiology of fungal pathogens. The following recommendations for management of candidemia are common to all three guidelines. Any positive blood culture for Candida indicates disseminated infection or deep organ infection and requires antifungal therapy. Treatment should be initiated as soon as possible. Removal or changing of central venous catheters or other foreign material in the bloodstream is recommended whenever possible. Ophthalmological examination for exclusion of endophthalmitis and follow-up blood cultures during therapy are also recommended. Duration of therapy should be 14 days after clearance of blood cultures and resolution of symptoms. Consideration of surgical options and a prolonged antifungal treatment (weeks to months) are required when there is organ involvement. During the last decade several new antifungal agents were introduced into clinical practice. These innovative drugs showed convincing efficacy and favorable safety in randomized clinical trials. Consequently, they were integrated in recent therapeutic guidelines, often replacing former standard drugs as first-line options. Echinocandins have emerged as the generally preferred primary treatment in candidemia. The expert panel of ESCMID views fluconazole only as a marginally recommended therapy for this indication. The use of amphotericin B deoxycholate should be generally avoided because of toxicity.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Combined Modality Therapy; Critical Care; Echinocandins; Guidelines as Topic; Humans; Intensive Care Units

The widespread use of intravascular devices, such as central venous and hemodialysis catheters, in the past 2 decades has paralleled the increasing incidence of catheter-related bloodstream infections (CR-BSIs). Candida albicans is the fourth leading cause of hospital-associated BSIs. The propensity of C. albicans to form biofilms on these catheters has made these infections difficult to treat due to multiple factors, including increased resistance to antifungal agents. Thus, curing CR-BSIs caused by Candida species usually requires catheter removal in addition to systemic antifungal therapy. Alternatively, antimicrobial lock therapy has received significant interest and shown promise as a strategy to treat CR-BSIs due to Candida species. The existing in vitro, animal, and patient data for treatment of Candida-related CR-BSIs are reviewed. The most promising antifungal lock therapy (AfLT) strategies include use of amphotericin, ethanol, or echinocandins. Clinical trials are needed to further define the safety and efficacy of AfLT.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Catheter-Related Infections; Catheterization, Central Venous; Catheters, Indwelling; Clinical Trials as Topic; Echinocandins; Ethanol; Heparin; Humans; Iron Chelating Agents

Invasive fungal infections (IFIs) are responsible for significant morbidity and mortality, especially in immunocompromised patients and in those requiring admission to an intensive care unit. The epidemiology of IFI is changing, and an increment in non-Aspergillus filamentous fungi and non-Candida albicans species has been observed. The present paper reviews the epidemiology and diagnosis of IFIs. Regarding the treatment of IFIs, it focuses primarily on the role of liposomal amphotericin B in this setting. The main recommendations put forth by expert societies and groups are discussed.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Humans; Mycoses; Treatment Outcome

Candida osteomyelitis is a rare infection. We present 17 cases of Candida osteomyelitis from our institution and review 194 patients from the literature. The median age of patients was 57 ± 22 years (range, 18-90 years) with 68% male. Comorbidities associated with this infection include prior surgery (62%), broad-spectrum antibiotics (40%), central venous catheter insertion (19%), and immunosuppression (17%). The most common infecting species were Candida albicans (69%), Candida tropicalis (15%), and Candida glabrata (8%). Most initial antifungal regimens included amphotericin B (59%); however, fluconazole is increasingly being utilized for treatment of this infection (26%). Echinocandins were used infrequently (4%). Median length of treatment was 3 ± 4.5 months (mean, 4.2 months; range, 18 days to 36 months). The overall success rate of therapy was 91%, with 75% of patients cured by 6 months. The crude mortality rate was 12% with an attributable mortality rate of 6%.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Comorbidity; Echinocandins; Female; Fluconazole; Humans; Male; Middle Aged; Osteomyelitis; Risk Factors; Sex Distribution; Treatment Outcome; Young Adult

Invasive fungal infections are associated with significant morbidity and mortality in children. Optimal treatment strategies are yet to be defined.. This review aims to systematically identify and summarise the effects of different antifungal therapies in children with proven, probable or suspected invasive fungal infections.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1966 to September 2008), EMBASE (1980 to September 2008) and CINAHL (1988 to September 2008) without language restrictions. We also handsearched reference lists and abstracts of conference proceedings and scientific meetings, and contacted authors of included studies and pharmaceutical manufacturers.. We included randomised clinical trials (RCTs) comparing a systemic antifungal agent with a comparator (including placebo) in children (one month to 16 years) with proven, probable or suspected invasive fungal infection.. Two review authors independently applied selection criteria, performed quality assessment, and extracted data using an intention-to-treat approach. We synthesised data using the random-effects model and expressed results as relative risks (RR) with 95% confidence intervals (CIs).. We included seven trials of antifungal agents in children with prolonged fever and neutropenia (suspected fungal infection) and candidaemia or invasive candidiasis (proven fungal infection). Four trials compared a lipid preparation of amphotericin B with conventional amphotericin B (395 participants), one trial compared an echinocandin with a lipid preparation of amphotericin B (82 participants) in suspected infection; one trial compared an echinocandin with a lipid preparation of amphotericin B in children with candidaemia or invasive candidiasis (109 participants) and one trial compared different azole antifungals in children with candidaemia (43 participants). No difference in all-cause mortality and other primary endpoints (mortality related to fungal infection or complete resolution of fungal infections) were observed. No difference in breakthrough fungal infection was observed in children with prolonged fever and neutropenia.When lipid preparations and conventional amphotericin B were compared in children with prolonged fever and neutropenia, nephrotoxicity was less frequently observed with a lipid preparation (RR 0.43, 95% CI 0.21 to 0.90, P = 0.02) however substantial heterogeneity was observed (I(2) = 59%, P = 0.06). Children receiving liposomal amphotericin B were less likely to develop infusion-related reactions compared with conventional amphotericin B (chills: RR 0.37, 95% CI 0.21 to 0.64, P = 0.0005). Children receiving a colloidal dispersion were more likely to develop such reactions than with liposomal amphotericin B (chills: RR 1.76, 95% CI 1.09 to 2.85, P = 0.02). The rate of other clinically significant adverse reactions attributed to the antifungal agent (total reactions; total reactions leading to treatment discontinuation, dose reduction or change in therapy; hypokalaemia and hepatotoxicity) were not significantly different. When echinocandins and lipid preparations were compared, the rate of clinically significant adverse reactions (total reactions; total reactions leading to treatment discontinuation, dose reduction or change in therapy) were not significantly different.. Limited paediatric data are available comparing antifungal agents in children with proven, probable or suspected invasive fungal infection. No differences in mortality or treatment efficacy were observed when antifungal agents were compared. Children are less likely to develop nephrotoxicity with a lipid preparation of amphotericin B compared with conventional amphotericin B. Further comparative paediatric antifungal drug trials and epidemiological and pharmacological studies are required highlighting the differences between neonates, children and adults with invasive fungal infections.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Echinocandins; Fever; Humans; Infant; Mycoses; Neutropenia; Randomized Controlled Trials as Topic

The need for new options for the treatment of invasive candidiasis has fuelled the use of antibodies in combination with conventional antifungal therapy. After a long period of time in which antibodies were considered irrelevant in the resistance against invasive candidiasis, it was demonstrated that a number of antibodies or their engineered derivatives directed against Candida albicans cell-wall polysaccharides and glycopeptides, as well as against some protein epitopes, confer protection against invasive candidiasis. This has confirmed this approach as a new strategy for the prophylaxis of invasive candidiasis. Of particular interest is Mycograb, a human recombinant monoclonal antibody that inhibits heat shock protein 90, and has been administrated in combination with lipid-associated amphotericin B to patients with invasive candidiasis, and the fungicidal anti-beta-glucan antibodies induced by the glycoconjugate vaccine composed of a beta-glucan polysaccharide conjugated with the diphtheria toxoid CRM 197. However, despite the promising data obtained in vitro and in animal models, at present there is very little clinical experience on the use of antibodies in Candida immunoprophylaxis.

Topics: Adult; Amphotericin B; Animals; Antibodies, Fungal; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Fungal; Bacterial Proteins; Candida albicans; Candidiasis; Caspofungin; Child; Combined Modality Therapy; Double-Blind Method; Drug Evaluation, Preclinical; Echinocandins; Fungal Vaccines; Humans; Immunization, Passive; Lipopeptides; Mice; Mycoses; Randomized Controlled Trials as Topic

Invasive fungal infection is an important cause of mortality and morbidity in very low birthweight (VLBW) infants. Extremely preterm and extremely low birthweight infants are at highest risk because of the intensive and invasive nature of the care that these infants receive. Additional specific risk factors include prolonged use of parenteral nutrition and exposure to broad-spectrum antibiotics and histamine type 2 receptor blockers. Diagnosis is difficult and often delayed, and this may contribute to the high levels of deep-organ dissemination and associated mortality and morbidity. The most commonly used antifungal agents are amphotericin B and fluconazole. Recent research has assessed the value of early empirical and prophylactic treatment. However, although systemic antifungal prophylaxis reduces the incidence of invasive fungal infection, there is no evidence of effect on mortality. Concern exists about the impact that widespread use of prophylaxis may have on the emergence of antifungal resistance.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Catheterization, Central Venous; Device Removal; Female; Fluconazole; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Intensive Care, Neonatal; Male; Microbial Sensitivity Tests

Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting particularly in the intensive care unit (ICU).. To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and an European expert panel discussion.. Empiric and directed treatment for invasive candidiasis are predicated on the hemodynamic status of the patient. Unstable patients may benefit from broad-spectrum antifungal agents, which can be narrowed once the patient has stabilized and the identity of the infecting species is established. In stable patients, a more classical approach using fluconazole may be satisfactory provided that the patient is not colonized with fluconazole resistant strains or there has been recent past exposure to an azole (<30 days). In contrast, pre-emptive therapy is based on the presence of surrogate markers.

Topics: Amphotericin B; Antifungal Agents; Bacteremia; Candida albicans; Candidiasis; Fluconazole; Humans; Intensive Care Units

To describe a rare case of early-onset Candida parapsilosis infection after laser in situ keratomileusis (LASIK) and review the published reports of post-LASIK fungal infections.. A 32-year-old woman presented with interface infiltration in the central interface in the right eye 2 days after LASIK surgery. The right eye flap was lifted, and the opacities were scraped. Two days later, a 3- x 3-mm-dense oval opacity and diffuse hazes were noted. Surgical intervention was arranged because of suspicion of interface infectious keratitis.. After an apparent post-LASIK keratitis with related interface inflammation failed to respond to medical therapy, corneal culture results were positive for C. parapsilosis 2 weeks 6 days after presentation. The patient was started on topical drops of amphotericin B 0.15% every hour after the smear showed the presence of yeast. The opacities decreased, and the topical antifungal drops were tapered. One month later, her uncorrected visual acuity recovered to 20/20.. Candida parapsilosis interface keratitis after LASIK may occur in the early phase. Early diagnosis and proper treatment can result in good outcome.

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Corneal Opacity; Drug Administration Schedule; Female; Humans; Keratitis; Keratomileusis, Laser In Situ; Ophthalmic Solutions

Candiduria is a hospital-associated infection and a daily problem in the intensive care unit. The treatment of asymptomatic candiduria is not well established and the use of amphotericin B bladder irrigation (ABBI) is controversial. The aim of this systematic review was to determine the best place for this therapy in practice.. The databases searched in this study included MEDLINE, EMBASE, Web of Science, and LILACS (January 1960-June 2007). We included manuscripts with data on the treatment of candiduria using ABBI. The studies were classified as comparative, dose-finding, or non-comparative.. From 213 studies, nine articles (377 patients) met our inclusion criteria. ABBI showed a higher clearance of the candiduria 24 hours after the end of therapy than fluconazole (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.32-1.00). Fungal culture 5 days after the end of both therapies showed a similar response (OR 1.51, 95% CI 0.81-2.80). The evaluation of ABBI using an intermittent or continuous system of delivery showed an early candiduria clearance (24 hours after therapy) of 80% and 82%, respectively (OR 0.87, 95% CI 0.52-1.36). Candiduria clearance at >5 days after the therapy showed a superior response using continuous bladder irrigation with amphotericin B (OR 0.52, 95% CI 0.29-0.94). The use of continuous ABBI for more than 5 days showed a better result (88% vs. 78%) than ABBI for less than 5 days, but without significance (OR 0.55, 95% CI 0.34-1.04).. Although the strength of the results in the underlying literature is not sufficient to allow the drawing of definitive conclusions, ABBI appears to be as effective as fluconazole, but it does not offer systemic antifungal therapy and should only be used for asymptomatic candiduria.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Fluconazole; Humans; Randomized Controlled Trials as Topic; Therapeutic Irrigation; Urinary Bladder; Urinary Tract Infections; Urine

In neonatal intensive care units, deep fungal disease due to Candida spp. are an important clinical problem, partly due to the increasing prevalence of Candida disease and also to the high associated and constant morbimortality; both factors are independently maintained though there has been a significant improvement in the management of neonatal patients.. To define the therapeutic use of micafungin for the treatment of neonatal invasive candidiasis.. We use a review of biomedic data bases namely Medline and EMBASE.. Micafungin is the latest introduced echinocandin. It has a wide spectrum of activity and covers Candida albicans and non-albicans Candida species. It has scarce drugs interactions and is devoid of toxicity, being an attractive approach for the treatment of invasive candidiasis (without meningitis, endocarditis and endophthalmitis). Althought the European Medicines Agency approved in 2008 the use of Micafungin for the treatment of invasive candidiasis in children, the available clinical experience is limited and currently more clinical studies are warranted to define its efficacy and safety in neonates.

Topics: Adolescent; Adult; Age Factors; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Clinical Trials as Topic; Echinocandins; Female; Fungemia; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lipopeptides; Male; Meta-Analysis as Topic; Micafungin; Multicenter Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies

Invasive fungal infections are a major cause of mortality among patients at risk. Treatment guidelines vary on optimal treatment strategies. We aimed to determine the effects of different antifungal therapies on global response rates, mortality and safety.. We searched independently and in duplicate 10 electronic databases from inception to May 2009. We selected any randomized trial assessing established antifungal therapies for confirmed cases of invasive candidiasis among predominantly adult populations. We performed a meta-analysis and then conducted a Bayesian mixed treatment comparison to differentiate treatment effectiveness. Sensitivity analyses included dosage forms of amphotericin B and fluconazole compared to other azoles.. Our analysis included 11 studies enrolling a total of 965 patients. For our primary analysis of global response rates, we pooled 7 trials comparing azoles to amphotericin B, Relative Risk [RR] 0.87 (95% Confidence Interval [CI], 0.78-0.96, P = 0.007, I2 = 43%, P = 0.09. We also pooled 2 trials of echinocandins versus amphotericin B and found a pooled RR of 1.10 (95% CI, 0.99-1.23, P = 0.08). One study compared anidulafungin to fluconazole and yielded a RR of 1.26 (95% CI, 1.06-1.51) in favor of anidulafungin. We pooled 7 trials assessing azoles versus amphotericin B for all-cause mortality, resulting in a pooled RR of 0.88 (95% CI, 0.74-1.05, P = 0.17, I2 = 0%, P = 0.96). Echinocandins versus amphotericin B (2 trials) for all-cause mortality resulted in a pooled RR of 1.01 (95% CI, 0.84-1.20, P = 0.93). Anidulafungin versus fluconazole resulted in a RR of 0.73 (95% CI, 0.48-1.10, P = 0.34). Our mixed treatment comparison analysis found similar within-class effects across all interventions. Adverse event profiles differed, with amphotericin B exhibiting larger adverse event effects.. Treatment options appear to offer preferential effects on response rates and mortality. When mycologic data are available, therapy should be tailored.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Anidulafungin; Antifungal Agents; Azoles; Candidiasis; Echinocandins; Fluconazole; Humans; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult

Invasive candidiasis is a common nosocomial infection among critically ill patients, constitutes an important cause of sepsis, and is associated with significant morbidity and mortality. The Infectious Diseases Society of America (IDSA) has created evidence-based guidelines for the management of invasive candidiasis. However, several new antifungal agents with excellent activity against Candida spp. and favourable safety profiles have been introduced successfully in the clinical setting since the IDSA guidelines were published in late 2003. Further, the role of antifungals is not entirely clear in the intensive care unit (ICU) setting. Therefore, this article discusses daily problems in the prophylaxis and treatment of invasive candidasis in interdisciplinary ICUs.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Echinocandins; Fluconazole; Humans; Intensive Care Units; Itraconazole; Pyrimidines; Risk Factors; Triazoles; Voriconazole

To compare available antifungal treatments for invasive candidiasis, a leading cause of nosocomial bloodstream infections.. We performed a systematic review and meta-analysis of randomized controlled trials that compared different antifungal agents for the treatment of candidemia and other forms of invasive candidiasis. Two reviewers independently appraised the quality of trials and extracted data. The primary outcome was all-cause mortality, and secondary outcomes were microbiological failure, treatment failure, and adverse events. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled.. Of the 15 included trials, 9 compared fluconazole with other drugs (amphotericin B, itraconazole, or a combination of fluconazole and amphotericin B), 4 compared echinocandins with other drugs (fluconazole, amphotericin B, liposomal amphotericin B), 1 compared micafungin and caspofungin, and 1 compared amphotericin B plus fluconazole and voriconazole. No difference in mortality was observed with fluconazole vs amphotericin B (RR, 0.92; 95% CI, 0.72-1.17); however, the rate of microbiological failure increased in the fluconazole arm (RR, 1.52; 95% CI, 1.12-2.07). Anidulafungin decreased the rate of microbiological failure compared with fluconazole (RR, 0.50; 95% CI, 0.29-0.86) with fewer adverse events. Caspofungin was comparable to amphotericin B in mortality and efficacy, with fewer adverse events requiring discontinuation (RR, 0.11; 95% CI, 0.04-0.36). Micafungin was comparable to liposomal amphotericin B in mortality.. All assessed antifungal agents showed similar efficacy, but the rate of microbiological failure increased with fluconazole vs amphotericin B or anidulafungin. Amphotericin B is associated with a higher rate of adverse events than fluconazole and echinocandins.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Confidence Intervals; Drug Therapy, Combination; Echinocandins; Fluconazole; Humans; Itraconazole; Lipopeptides; Lipoproteins; Micafungin; Odds Ratio; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole

Diabetes mellitus (DM) has been considered to predispose to candidiasis. While poor glycemic control increases the risk of superficial candidiasis (especially oral candidiasis), invasive candidiasis is not related to DM. Invasive candidiasis is diagnosed by combination of clinical manifestation, laboratory findings and isolation of Candida spp. Strategy of treatment for invasive candidiasis is consist of prophylactic, empiric and targeted therapy. MCFG, FLCZ and AMPH-B are recommended as first line drugs for invasive candidiasis, and L-AMB, VRCZ, ITCZ are considered as alternative drugs in Japanese guideline.

Topics: Amphotericin B; Antifungal Agents; Antigens, Fungal; beta-Glucans; Biomarkers; Candida; Candidiasis; Diabetes Complications; Echinocandins; Fluconazole; Humans; Lipopeptides; Micafungin; Proteoglycans

Invasive candidiasis has become a public health problem due to the high associated rates of morbidity and mortality. As in other systemic infections, accurate and early diagnosis is essential. Despite its limited sensitivity (50%), blood culture continues to be the most effective technique for the diagnosis of candidemia. New culture-independent techniques have been marketed with the aim of improving diagnostic yield. Among these techniques, the most notable are (1-3)-beta-D-glucan and anti-germ-tube antibody detection. However, the best option to optimize the diagnosis of invasive candidiasis seems to be the combination of two techniques that detect antigen, antibodies, (1-3)-beta-D-glucan or DNA. Fluconazole, and sometimes amphotericin B, remain the antifungal agents of choice for the treatment of candidiasis. In the last few years, new antifungal agents have been introduced with the aim of improving the prognosis of some clinical presentations of this disease. The echinocandins and second-generation triazoles show greater antifungal activity than fluconazole. Moreover, clinical trials of candidiasis in different localizations have shown that these drugs have excellent efficacy and safety profiles. The potential for drug interactions with some of these antifungal agents is considerable. The contribution of the new antifungal drugs in the treatment of candidiasis should be defined in the near future.

Topics: Amphotericin B; Antibodies, Fungal; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Fungal; Candida; Candidiasis; Clinical Trials as Topic; DNA, Fungal; Drug Interactions; Echinocandins; Fungemia; Humans; Mycology; Mycoses; Triazoles; Yeasts

The most frequent invasive fungal infections in critically ill patients are invasive candidiasis, among which is candidemia. In the last few years, these infections have become more common in intensive care units (ICU), including those produced by species other than Candida albicans. This phenomenon may lead to the development of species resistant to antifungal agents. To start the most appropriate treatment, early diagnosis of the infection is essential, which would reduce empirical antibiotic treatment and increase the proportion of advanced or directed antibiotic therapy. Given the poor reliability of the available diagnostic techniques, new strategies are currently being employed in the ICU, such as the use of scores to evaluate the presence of fungal infections. The therapeutic arsenal against these infections has been increased and the introduction of anidulafungin represents the addition of a highly appropriate drug for the treatment of invasive candidiasis in immunocompetent critically ill patients.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Candidiasis; Clinical Trials as Topic; Critical Illness; Cross Infection; Drug Therapy, Combination; Echinocandins; Fluconazole; Fungemia; Humans; Immunocompetence; Intensive Care Units; Itraconazole; Practice Guidelines as Topic

Until relatively recently, the treatment available for invasive fungal infections in hematological patients consisted of amphotericin B and azoles. Each of these groups had limitations and secondary effects. The echinocandins are a new class of antifungal agent that has shown promising results in the treatment of numerous invasive fungal infections. Anidulafungin is a new echinocandin that, in addition to showing potent in vitro activity against Aspergillus spp. and Candida spp. (including fluconazole- and amphotericin B-resistant microorganisms), also provides some advantages over other candins. In humans, these drugs are degraded through biotransformation rather than a metabolic process. No drug interactions have been found. In hematological patients, anidulafungin would play a "potential" role as empirical therapy in febrile neutropenia, as is the case of caspofungin. Given the epidemiology of Candida infection in these patients, anidulafungin could be used as initial therapy in candidemia before starting treatment with oral flucozanole, if indicated by the fungigram. This drug would also be indicated in the treatment of invasive Aspergillus spp. infections in patients with hepatic or renal insufficiency or in those taking concomitant medications. The available in vitro studies also suggest an important role for this drug in combinations of antifungal agents. Given the excellent safety profile and absence of interactions of anidulafungin, this drug will undoubtedly be of great utility in the management of difficult-to-treat mycotic infections in hematological patients.

Topics: Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Azoles; Candidiasis; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Therapy, Combination; Echinocandins; Fungemia; Hematologic Diseases; Hematologic Neoplasms; Humans; Inactivation, Metabolic; Kidney Diseases; Liver Diseases; Mice; Neutropenia; Risk Factors

Bloodstream infections caused by Candida spp. are increasingly recognised in critically ill adult and paediatric individuals, with significant associated morbidity and mortality. Candida albicans is the single most common fungal species to cause nosocomial infections. However, non-C. albicans spp., including Candida glabrata and Candida krusei, which are less susceptible to fluconazole, have become more common. Until the 1980s, the therapeutic possibilities for invasive candidosis were limited to amphotericin B, but with the advent of new antifungal agents, such as azoles and echinocandins, less toxic therapeutic options have become available and there are now possibilities for prevention and optimised therapy for documented Candida infections. In this review, the currently available options for the treatment of candidaemia and invasive candidosis are discussed with regard to the role of liposomal amphotericin B in comparison with the echinocandins and azoles.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candidiasis; Caspofungin; Critical Illness; Cross Infection; Drug Therapy, Combination; Echinocandins; Fungemia; Humans; Lipopeptides

Fungal urinary tract infections (funguria) are rare in community medicine, but common in hospitals where 10 to 30% of urine cultures isolate Candida species. Clinical features vary from asymptomatic urinary tract colonization (the most common situation) to cystitis, pyelonephritis, or even severe sepsis with fungemia. The pathologic nature of funguria is closely related to host factors, and management depends mainly on the patient's underlying health status. Microbiological diagnosis of funguria is usually based on a fungal concentration of more than 10(3)/mm(3) in urine. No cutoff point has been defined for leukocyte concentration in urine. Candida albicans is the most commonly isolated species, but previous antifungal treatment and previous hospitalization affect both species and susceptibility to antifungal agents. Treatment is recommended only when funguria is symptomatic or in cases of fungal colonization when host factors increase the risk of fungemia. The antifungal agents used for funguria are mainly fluconazole and amphotericin B deoxycholate, because other drugs have extremely low concentrations in urine. Primary and secondary preventions are essential. The reduction of risk factors requires removing urinary catheters, limiting antibiotic treatment, and optimizing diabetes mellitus treatment.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Cross Infection; Cystitis; Deoxycholic Acid; Drug Combinations; Female; Fluconazole; Fungemia; Fungi; Health Status; Hospital Mortality; Humans; Male; Mycoses; Primary Prevention; Pyelonephritis; Risk Factors; Urinary Catheterization; Urinary Tract Infections; Urine

Neonates with gastrointestinal diseases and extremely preterm infants are at highest risk for developing invasive fungal infections. Candida species are commensal organisms that colonize skin and mucosal surfaces as well as adhere to catheter surfaces. Due to the immature immune system of neonates including compromise of the developing barrier defenses of the skin or mucosal membranes, Candida can invade into the bloodstream and disseminate, often making these infections difficult to eradicate. Treatment of bloodstream infections uniquely involves both starting antifungal therapy and removing central venous catheters. Liposomal amphotericin formulations and echinochandins are currently being studied in neonates. Prevention for high risk patients is now feasible with fluconazole prophylaxis.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Therapy, Combination; Echinocandins; Fluconazole; Fungal Proteins; Humans; Infant, Newborn; Mycoses; Peptides, Cyclic; Treatment Outcome

Candida endophthalmitis is a sight-threatening manifestation of disseminated candidiasis. The occurrence of endogenous candida endophthalmitis in patients with candidemia has ranged from 0-45% in the published literature. In critically ill patients, it has even been associated with increased mortality. In recent years, use of newer antifungal therapies for invasive candidiasis has increased given the rise in infections with non-albicans species of Candida. To identify current practices of the management of endogenous candida endophthalmitis and relevant antifungal drug research in this disease state, we conducted a MEDLINE search (1967-2006) and bibliographic search of the English-language literature. Treatments for candida endophthalmitis have not been evaluated through well-designed, well-powered clinical trials. Data have mainly been presented in case reports, case series, animal studies, pharmacokinetic studies, and as small subsets of larger trials. Traditional systemic therapies have been amphotericin B with or without flucytosine or fluconazole. Cure rates with antifungal drugs alone appear to be much higher in patients with chorioretinitis than in endophthalmitis with vitreal involvement. Pars plana vitrectomy with or without intravitreal amphotericin B injections has been advocated particularly for patients with moderate-to-severe vitritis and substantial vision loss. Information on new antifungal agents for endophthalmitis is limited, despite increasing use in patients with candidemia. Voriconazole may be a particularly attractive agent to consider for infections with fluconazole-resistant, voriconazole-susceptible strains. The current patchwork of animal studies and small patient reports provide clinicians with some insight into the role of newer agents in the treatment of candida endophthalmitis. In general, it appears that chorioretinitis infections can be more readily cured with most systemic antifungal agents, whereas more aggressive treatment, often including vitrectomy with or without intra-vitreal antifungal administration, is needed for patients with endophthalmitis with vitritis.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Echinocandins; Endophthalmitis; Fluconazole; Flucytosine; Humans; Pyrimidines; Risk Factors; Triazoles; Voriconazole

Renal, liver, heart and lung transplantation are now considered to be the standard therapeutic interventions in patients with end-stage organ failure. Infectious complications following transplantation are relatively common due to the transplant recipients overall immunosuppressed status. The incidence of invasive mycoses following solid organ transplant ranges from 5 to 42% depending on the organ transplanted. These mycoses are associated with high overall mortality rates. Candida and Aspergillus spp. produce most of these infections. This article will review the risk factors, clinical presentation and treatment of invasive fungal infections in solid organ transplant patients, and evaluate the role of prophylactic therapy in this group of patients.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Caspofungin; Clinical Trials as Topic; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Echinocandins; Fluconazole; Humans; Incidence; Lipopeptides; Organ Transplantation; Peptides, Cyclic; Postoperative Complications; Premedication

Invasive fungal infections (IFIs) can cause significant morbidity and mortality in patients after haematopoietic stem cell transplantation. The two most notorious pathogenic fungal species in this group of patients are Candida and Aspergillus. Risk factors for IFIs include: prolonged neutropaenia; fungal overgrowth and conditioning regiment-related mucositis; graft versus host disease; and steroid therapy. Clinical manifestations can be protean, and radiological changes are frequently nonspecific. Diagnostic methods include culture- and nonculture-based techniques. Some experts recommend IFI prophylaxis in the high-risk groups, such as patients with severe graft versus host disease who require prolonged immunosuppressive therapy or patients with a previous history of aspergillosis. Treatment options include therapy with azoles, including the newer agent voriconazole, amphotericin and caspofungin.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Caspofungin; Drug Administration Schedule; Echinocandins; Humans; Lipopeptides; Peptides, Cyclic; Postoperative Complications; Premedication; Pyrimidines; Randomized Controlled Trials as Topic; Triazoles; Voriconazole

Amphotericin B deoxycholate has been the 'gold standard' treatment for invasive fungal infections for over 40 years. Driven to improve on the renal toxicity of amphotericin B deoxycholate, extensive pharmaceutical research has led to the development of several new antifungals including lipid formulations of amphotericin B, broad-spectrum azoles and echinocandins. Compared with amphotericin B deoxycholate, the lipid formulations of amphotericin B (amphotericin B lipid complex, amphotericin B colloidal dispersion and liposomal amphotericin B) share distinct advantages in improved drug safety, in particular reduced incidence and severity of amphotericin B deoxycholate-related nephrotoxicity. However, the lipid formulations of amphotericin B are significantly more expensive than amphotericin B deoxycholate and, as for many of these new antifungals, there are as yet insufficient published studies to guide clinicians. This paper examines aspects of safety, efficacy, and health economic data for the lipid formulations of amphotericin B in particular, in order to provide a rationale to justify substituting amphotericin B deoxycholate with the lipid formulations of amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Chemistry, Pharmaceutical; Colloids; Deoxycholic Acid; Drug Combinations; Humans; Liposomes; Phosphatidylcholines; Phosphatidylglycerols; Treatment Outcome

Emerging fungal infections represent a serious problem in an immunocompromised host. Rapid developments in in vitro antifungal susceptibility testing and the availability of several new antifungal agents have provided excellent opportunities to treat infections that are caused by various Candida spp. and to some extend by Aspergillus spp. However, recently the epidemiology of fungal infections has significantly changed and several new pathogens have emerged. This article attempts to summarise the available data on the management of emerging infections with fungal infections that have recently gained importance. Updated recommendations on antifungal treatment are also discussed.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Clinical Trials as Topic; Drug Administration Schedule; Drug Resistance, Fungal; Drug Therapy, Combination; Fluconazole; Humans; Immunocompromised Host; Mucormycosis; Practice Guidelines as Topic; Pyrimidines; Triazoles; Voriconazole

The high morbidity, mortality, and healthcare costs associated with the invasive fungal infections, especially in the critical care setting, is of importance since the prophylactic, empiric, and pre-emptive therapy interventions, based on early identification of risk factors, is of common occurrence. In the last years alone there have been important developments in antifungal pharmacotherapy. Evidence-based studies using new antifungal agents are now emerging as important players in the pharmacotherapy of invasive fungal infections in seriously ill and difficult patients. However, data on critically ill patients are more limited and usually recovered from general studies. This study shows the benefits obtained by the new antifungal agents on different clinical situations in critical care units. The increasing number of non-C. albicans species and the high mortality rates in these settings suggest that the application of early de-escalation therapy in critically ill patients with fungal infection should be mandatory. The possibility of using antifungal combination therapy in these types of patients should be considered.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Critical Illness; Cross Infection; Deoxycholic Acid; Drug Combinations; Fluconazole; Humans; Intensive Care Units; Mycoses; Pyrimidines; Randomized Controlled Trials as Topic; Triazoles; Voriconazole

Caspofungin, micafungin and anidulafungin are three drugs of the echinocandin class of antifungals available for intravenous treatment of invasive candidiasis and aspergillosis. They exhibit high in vitro and in vivo activities against Candida spp. and Aspergillus spp. In various clinical studies investigating candidemia and invasive candidiasis, Candida esophagitis, and fever in neutropenia, the clinical efficacy of the echinocandin tested was similar to that of established antifungals. Antifungal activity against strains no longer susceptible to conventional antifungal agents, such as fluconazole and amphotericin B suggests that echinocandins can be used as salvage therapy in life-threatening fungal infections. There is no cross-resistance to other antifungals. Excellent safety and tolerability of treatment with caspofungin has been documented over a total of 4.3 million patient days. Echinocandins are poor substrates of the cytochrome P450 enzyme family and can be safely co-administered with most drugs without the need for dosage adaptation. No dose reduction is required in renal impairment. A reduction in the daily maintenance dose has been recommended for caspofungin, but not for micafungin and anidulafungin in patients presenting with mild to moderate hepatic failure.

Topics: Actins; Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Area Under Curve; Candidiasis; Caspofungin; Drug Resistance, Microbial; Echinocandins; Humans; Lipopeptides; Lipoproteins; Liver; Liver Failure; Micafungin; Models, Chemical; Peptides, Cyclic; Rats

Over the last two decades, systemic fungal infections have emerged to play a primary role in hospital-acquired infections. C. albicans is involved in 75% of neonatal candidiasis; however, the incidence of infection from C. parapsilosis is also increasing significantly. The higher incidence observed in the high-risk group of very low birth weight (VLBW) infants is linked to their special physical characteristics and the diagnostic and therapeutic invasive procedures they undergo. Colonization is a relevant risk factor depending on the colonized site , the fungal species and the type of colonization. Serological tests have a low specificity and sensitivity; in many cases, they do not distinguish between colonization and infection. Blood culture, although the best diagnostic test for determining systemic infection, can result negative, even in cases of deep organ involvement. In addition, fungi grow more slowly than bacteria in cultures. So, the difficulty in diagnosing systemic candidiasis and its aspecific clinical features may make empirical therapy appropriate. Amphotericin B (AmB) alone or combined with 5-fluorocytosine remains the drug of choice. Fluconazole represents a valid alternative. Recently developed new formulations of amphotericin incapsulated in liposomes can avoid possible adverse effects. Prognosis depends on the specific micro-organism involved; mortality is higher in the presence of C. albicans. As prognosis is associated with high mortality, prevention measures to reduce risk factors are of critical importance.

Topics: Age Factors; Amphotericin B; Antifungal Agents; Candidiasis; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Incidence; Infant, Newborn; Infant, Very Low Birth Weight; Prognosis; Risk Factors; Sensitivity and Specificity

Chronic disseminated candidiasis (CDC) is a form of invasive fungal infection that occurs most commonly in patients with acute leukemia treated with chemotherapy. Recent studies have provided evidence for diagnostic alternatives to invasive procedures and more therapeutic options for the management of this complication. In order to put diagnostic criteria and methodological approach to the disease into the perspective of developing strategies for therapy, all relevant studies published in the English literature over the last 30 years were examined.. The English-language articles located through MEDLINE (1966 to present) and from selected bibliographies.. There is increased recognition of CDC as complication of treatment with chemotherapy in patients with acute leukemia. Liver biopsy may not always be revealing or feasible to perform in some patients. Among the imaging modalities, magnetic resonance imaging has obtained preeminence as a non-invasive tool for the diagnosis of hepatosplenic fungal infections. Administration of amphotericin B (Amp B) in relatively large cumulative doses is needed to ensure appropriate control of the infection and prevention of future relapse. Patients intolerant of, or refractory to conventional Amp B have been successfully salvaged using fluconazole or lipid formulations of Amp B. A constellation of clinical, laboratory and radiologic parameters should be used to determine response and efficacy of therapy. There is sufficient evidence to support the safety and feasibility of continuing chemotherapy for acute leukemia in conjunction with antifungal treatment in patients diagnosed with CDC.. The development of CDC in patients with acute leukemia does not preclude further chemotherapy or constitute contraindication for bone marrow transplantation. Knowledge of the course and pattern of evolution of the disease and adopting aggressive therapeutic approach will likely reduce the morbidity and mortality from this complication.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Chronic Disease; Fluconazole; Humans; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Salvage Therapy; Time Factors

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Caspofungin; Deoxycholic Acid; Drug Combinations; Echinocandins; Hematologic Neoplasms; Humans; Itraconazole; Lipopeptides; Liposomes; Mycoses; Organ Transplantation; Peptides, Cyclic; Pyrimidines; Risk Factors; Stem Cell Transplantation; Triazoles; Voriconazole; Zygomycosis

Recent years have seen the development of the concept of combination therapy for treating severe fungal sepsis. The advantages of this approach are a potential improvement in patient survival and a reduction in the chance of resistance developing to each of the single agents. The disadvantage is that combining drugs may increase the chance of toxicity. Mycograb is a genetically recombinant antibody against fungal heat shock protein 90 (hsp90) which is poised to become the mainstay of combination therapy. This paper presents data on how hsp90 is important to fungi and what role it might play in human disease with possible interactions with interleukin 6 and nitric oxide. There is discussion of preclinical data demonstrating synergy in vitro between Mycograb and amphotericin B and caspofungin. The progress of Mycograb through a Phase II pharmacokinetic study when used in escalating doses with a liposomal amphotericin B preparation has also been reviewed. The concepts behind a Phase II pivotal study, where Mycograb or a placebo was given in combination with a liposomal amphotericin B drug for five days for the treatment of disseminated candidiasis are discussed.

Topics: Amphotericin B; Animals; Antibodies, Fungal; Antifungal Agents; Candidiasis; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Synergism; Heat-Shock Proteins; Humans; Recombinant Proteins

The incidence of candidiasis has risen in neonatal intensive care units as advances in medical therapy have allowed for increased survival of extremely preterm neonates. The mortality of candidiasis has been reported to be 20% by several multi-centre studies. Definitive guidance for prophylaxis and treatment is hindered by lack of large, multi-centre, randomised controlled trials. Systemic prophylaxis is currently not recommended for any neonatal population, and amphotericin B deoxycholate continues to be used as first-line therapy for the treatment of invasive disease.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Deoxycholic Acid; Drug Combinations; Fluconazole; Humans; Infant, Low Birth Weight; Infant, Newborn; Randomized Controlled Trials as Topic; Risk Factors

An unusual central venous catheter (CVC)-related infection caused by Candida membranaefaciens in a patient with non-Hodgkin's lymphoma is described. Clinical signs and microbiological results observed in this case may support the hypothesis of an emerging CVC-related fungaemia, because of new azole-resistant yeast, successfully treated with liposomal amphotericin B. To date C. membranaefaciens (the teleomorph of Pichia membranaefaciens) has traditionally been considered non-pathogenic and this report seems to be the first case of systemic fungal infection. We believe that another fungus can be added to the list of opportunistic strains.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Catheterization, Central Venous; Drug Resistance, Fungal; Hodgkin Disease; Humans; Opportunistic Infections; Prosthesis-Related Infections

Topics: Amphotericin B; Candidiasis; Cross Infection; Female; Fungemia; Humans; Incidence; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Male; Risk Assessment; Survival Rate; United States

Catheter removal is now the standard recommendation of catheter-related fungemia even when tunneled devices are used. However, in the clinical practice, this procedure is not always without risks. Antibiotic-lock technique can resolve many cases of catheter-related bacteraemia, but cure of catheter-related candidemia by this method has been attempted in very few instances, reviewed in this article. Herein, we report a case of non-complicated Candida glabrata fungemia related to a Hickman catheter used for parenteral nutrition, cured with intraluminal amphotericin B in addition to systemic therapy. This case demonstrates that 'antifungal-lock therapy' can be effectively used in selected cases of catheter-related candidemia.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Catheterization, Central Venous; Catheters, Indwelling; Equipment Contamination; Female; Fluconazole; Fungemia; Humans; Parenteral Nutrition

Reported here is the case of a 72-year-old man who was diagnosed with Candida glabrata prosthetic mitral valve endocarditis and treated successfully with fluconazole plus caspofungin after he refused and was determined unfit for surgery. Initial treatment with intravenous amphotericin B resulted in acute renal impairment. Despite 8 days of intravenous fluconazole therapy, he remained fungemic. Caspofungin was added to the treatment regimen with subsequent sterilisation of blood culture. The patient was treated for 34 days with caspofungin and 41 days with fluconazole. He continued oral fluconazole after hospital discharge and remained well at follow-up 11 months later. The role of fluconazole and caspofungin in the treatment of Candida endocarditis is discussed.

Topics: Acute Kidney Injury; Aged; Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Drug Therapy, Combination; Echinocandins; Endocarditis; Fluconazole; Heart Valve Prosthesis; Humans; Lipopeptides; Male; Mitral Valve; Peptides, Cyclic; Prosthesis-Related Infections

Advances in neonatal management have led to considerable improvement in newborn survival. However, early (<72 hours) and late (>72 hours) onset systemic infections, both bacterial and fungal, remain a devastating complication and an important cause of morbidity and mortality in these babies. Most neonatal fungal infections are due to Candida species, particularly Candida albicans. The sources of candidiasis in NICU are often endogenous following colonization of the babies with fungi. About 10% of these babies get colonized in first week of life and up to 64% babies get colonized by 4 weeks of hospital stay. Disseminated candidiasis presents like bacterial sepsis and can involve multiple organs such as the kidneys, brain, eye, liver, spleen, bone, joints, meninges and heart. Confirming the diagnosis by laboratory tests is difficult and a high index of suspicion is required. The diagnosis of fungemia can be made definitely only by recovering the organism from blood or other sterile bodily fluid. Amphotericin B continues to be the mainstay of therapy for systemic fungal infections but its use is limited by the risks of nephrotoxicity and hypokalemia. Newer formulations of amphotericin B, namely the liposomal and the lipid complex forms, have recently become available and have been reported to have lesser toxicity. More recently Indian liposomal Amphotericin B derived from neutral lipids (L-Amp-LRC-1) has shown good response with less toxicity. A clinical trial with this preparation has shown to be safe and efficacious in neonatal fungal infections. Compared to other liposomal preparations, L-Amp-LRC-1 is effective at lower dose and is less expensive drug for the treatment of neonatal candidiasis.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Fluconazole; Humans; Infant, Newborn; Risk Factors

Cochleates are a novel lipid-based delivery vehicle consisting of crystalline phospholipid-cation structures that form spiral lipid sheets. They represent a new technology platform for oral delivery of clinically important drugs that possess poor oral bioavailability. Orally administered cochleates containing amphotericin B (CAMB) showed broad-spectrum activity in murine infection models of candidiasis, aspergillosis and cryptococcosis. Initial biodistribution studies of CAMB administered orally in mice demonstrated that cochleates delivered significant levels of AMB to target organs. The lipid particulate nature of cochleates also imparted reduced toxicity that mimics other lipid-amphotericin B complexes. Cochleates are a promising new vehicle for oral delivery of amphotericin B at therapeutic levels.

Topics: Administration, Oral; Amphotericin B; Animals; Candidiasis; Drug Delivery Systems; Humans; Phospholipids

Fungal infections are common in the newborn period, especially among premature neonates, and are responsible for considerable morbidity and mortality. Currently, three classes of antifungals are commonly used in the treatment of systemic fungal infections in neonates: the polyene macrolides (e.g. amphotericin B [deoxycholate and lipid preparations]); the azoles (e.g. fluconazole); and the fluorinated pyrimidines (e.g. flucytosine). The echinocandins (e.g. caspofungin and micafungin) are a newer class of antifungals which shows promise in this population.The available kinetic data on amphotericin B deoxycholate in neonates are derived from very small studies and exhibit considerable variability. There are no kinetic data available for the use of lipid preparations in this population and, again, much has been inferred from adult studies. The information available for flucytosine is also limited but appears similar to what is observed in adults. Fluconazole has the most neonatal pharmacokinetic data, which show slightly less variability than the other antifungals. Genomic factors which affect the metabolism of amphotericin B and fluconazole may explain some of the observed variability. Most of the data for the efficacy of antifungal drugs in neonates are derived from retrospective studies and case reports. The data for amphotericin B deoxycholate and flucytosine are limited. There are more data for the liposomal and lipid complex preparations of amphotericin B and for fluconazole in this population. These support the use of these drugs in neonates, but because of their largely noncomparative nature they can not define the optimal dosage or duration of therapy. Amphotericin B deoxycholate is primarily nephrotoxic. It also induces electrolyte abnormalities and is to a lesser degree cardiotoxic. This toxicity in neonates appears similar to published data in older children and adults. While the lipid preparations of amphotericin B owe their existence to a presumed decrease in toxicity, the observed toxicity in neonates appears to be equal to that seen with the deoxycholate, although it should be noted that the lipid preparations are usually given at much higher dosages. Fluconazole toxicity appears to be milder and less frequent in this population than is seen with amphotericin B. In the final analysis, we do not have sufficient data to define the pharmacokinetic profiles, optimal dose or duration of therapy, or toxicity for any of these compounds in neonates. F

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Clinical Trials as Topic; Drug Therapy, Combination; Echinocandins; Fluconazole; Flucytosine; Fungal Proteins; Humans; Infant, Newborn; Peptides; Peptides, Cyclic

We report the case of a 48-year-old man with a pseudocyst infected by Candida albicans, and review the relevant literature. The patient was successfully treated by a Roux-en-Y cystojejunostomy of the pseudocyst and adjunctive therapy with amphotericin B. Candida species isolated from a pancreatic pseudocyst or abscess should be considered pathogenic, and treated aggressively.

Topics: Amphotericin B; Anastomosis, Roux-en-Y; Antifungal Agents; Candida albicans; Candidiasis; Combined Modality Therapy; Humans; Jejunostomy; Male; Middle Aged; Pancreatic Pseudocyst

Bilateral fungal obstruction of the renal collecting system is rare in infancy. Treatment options include medical or surgical procedures. Reports of successful medical treatment with liposomal amphotericin B have been published but the duration of treatment is controversial. We report a 3-week-old preterm baby with myelomeningocele who had experienced acute renal failure related to bilateral renal fungus balls, which improved with percutaneous nephrostomy and 12 weeks of liposomal amphotericin B intravenously combined with 5-fluorocytosine orally for 9 weeks.

Topics: Acute Kidney Injury; Amphotericin B; Antifungal Agents; Candidiasis; Female; Flucytosine; Humans; Infant; Kidney Diseases; Liposomes; Time Factors

Systemic infection with Aspergillus fumigatus is an opportunistic disease that affects mainly immunocompromised hosts and is associated with a high mortality rate. We report a case of A. fumigatus endocarditis after an episode of thrombotic thrombocytopenic purpura. Diagnosis was established after sudden rupture of posterior papillary muscle of the normal native mitral valve. Soon after mitral valve replacement, Aspergillus endocarditis recurred, associated with multiple peripheral emboli, which necessitated a second operation.

Topics: Amphotericin B; Anti-Infective Agents; Aspergillosis; Aspergillus fumigatus; Candidiasis; Drug Resistance, Fungal; Embolism; Endocarditis; Fatal Outcome; Female; Heart Valve Prosthesis Implantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Itraconazole; Lung Diseases, Fungal; Middle Aged; Mitral Valve Insufficiency; Opportunistic Infections; Papillary Muscles; Postoperative Complications; Prednisolone; Pseudomonas Infections; Purpura, Thrombotic Thrombocytopenic; Recurrence; Rupture, Spontaneous; Shock, Septic; Sputum; Ultrasonography; Urinary Tract Infections

We present a case of an immunocompromised host who developed a Candida glabrata infection 20 years after her total knee arthroplasty. She was treated with extensive irrigation and debridement, followed by placement of an amphotericin B cement spacer supplemented with 2 months of oral variconazole. She ultimately underwent an above-knee amputation.

Topics: Adult; Amphotericin B; Amputation, Surgical; Anti-Bacterial Agents; Antifungal Agents; Candida glabrata; Candidiasis; Debridement; Female; Humans; Immunocompromised Host; Knee Prosthesis; Prosthesis-Related Infections; Reoperation; Therapeutic Irrigation; Vancomycin

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in neutropenic patients with leukemia and those undergoing hematopoietic stem cell transplant (HSCT). Two major IFIs are systemic candidiasis (including candidemia, chronic disseminated candidiasis and pneumonia) and invasive pulmonary aspergillosis. Recently, the incidence of the latter has been increasing. Three levels of diagnosis are specified in the Japanese guidelines for the diagnosis and treatment of IFIs. Proven fungal infections are diagnosed by histological/microbiological evidence of fungi at the site of infection or positive blood culture (fungemia). Clinically documented fungal infections are diagnosed by typical radiological findings such as halo sign on chest CT plus positive serological/molecular evidence of fungi such as Aspergillus galactomannan, beta-glucan or fungal DNA. Possible fungal infections are diagnosed by typical radiological findings or positive serological/molecular evidence of fungi. For patients with high risk such as those undergoing HSCT, antifungal prophylaxis using oral antifungal agents is recommended. For possible fungal infections, empiric therapy with fluconazole (FLCZ) or amphotericin B (AMPH) is recommended. For patients with proven fungal infections or clinically documented fungal infections, targeted therapy is warranted. In case of candidemia, the best choice is FLCZ (400 mg/day) or AMPH (0.5-0.7 mg/kg/day), and for invasive pulmonary aspergillosis, a higher dose of AMPH (1.0-1.5 mg/kg/day) is indicated. Micafungin (MCFG), recently licensed in Japan, is an active agent for both Candida and Aspergillus. This drug seems useful for empiric and targeted therapy of IFIs.

Topics: Amphotericin B; Aspergillosis; Candidiasis; Echinocandins; Fluconazole; Humans; Lipopeptides; Lipoproteins; Lung Diseases, Fungal; Micafungin; Neutropenia; Peptides, Cyclic; Practice Guidelines as Topic

Candidiasis and aspergillosis are the most common fungal infections in hematopoietic stem cell transplant recipients and other hematology/oncology patients. Strategies for reducing the morbidity and mortality associated with these infections include antifungal prophylaxis, empiric therapy in patients with persistent fever and neutropenia, and preemptive therapy. Antifungal therapies include amphotericin B deoxycholate, lipid formulations of amphotericin B, the triazoles (fluconazole, itraconazole, and voriconazole), and the echinocandins (caspofungin and the investigational agents micafungin and anidulafungin). Fluconazole is a reasonable choice for the treatment of invasive candidiasis if the patient has not previously received a triazole and the institution has a low incidence of triazole resistance. If resistance is a concern, an echinocandin, such as caspofungin, is an appropriate option. Voriconazole may be the initial choice in most patients with invasive aspergillosis. If patients are intolerant of or refractory to conventional therapy, effective alternatives include a lipid formulation of amphotericin B or an echinocandin.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Resistance, Fungal; Echinocandins; Fungal Proteins; Hematopoietic Stem Cell Transplantation; Humans; Liposomes; Mycoses; Neoplasms; Neutropenia; Peptides, Cyclic; Randomized Controlled Trials as Topic; Survival Analysis; Triazoles

Considering the significant morbidity and mortality associated with invasive fungal infections in immunocompromised patients, it is particularly important to make the diagnosis as early as possible and to make best use of the available antifungal drugs for prophylaxis and treatment. The newer antifungal drugs include the lipid products of amphotericin B, such as amphotericin B lipid complex (ABLC) and liposomal amphotericin B; voriconazole (a triazole); and caspofungin (an echinocandin). ABLC and liposomal amphotericin B are as effective as amphotericin B deoxycholate but are less nephrotoxic; ABLC is probably the drug of choice for zygomycosis. Voriconazole is approved for use in the treatment of invasive aspergillosis and may have a role in preventing breakthrough fungal infections in patients with persistent fever and neutropenia. Caspofungin is effective against both invasive aspergillosis and invasive candidiasis.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Caspofungin; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Resistance, Fungal; Echinocandins; Humans; Lipopeptides; Liposomes; Mycoses; Peptides, Cyclic; Phosphatidylcholines; Phosphatidylglycerols; Pyrimidines; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Triazoles; Voriconazole; Zygomycosis

Combination therapy with amphotericin B and flucytosine is considered to be the treatment of choice for cryptococcal infections. However, for other infections and combinations of antifungal infections, the data are less clear-cut. The concurrent use of amphotericin B with an azole has elicited controversy, given the potential of antimicrobial antagonism. The results of one recent candidemia study suggest that the potential antagonism may not be an issue; the combination of amphotericin B and fluconazole provided more effective clearance of Candida from the bloodstream than did fluconazole used alone. Several in vitro and animal studies have shown antagonism between the azoles and amphotericin B for aspergillosis. However, introduction of the new class of agents that target beta-glucan synthase (echinocandins) has invigorated the prospects of combination therapy. The echinocandins and polyenes are not antagonistic, and there is evidence that the echinocandins may provide additive to synergistic activity in combination with triazoles. For patients whose aspergillosis is progressing despite monotherapy, the addition of a second agent, such as an echinocandin, may be reasonable.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Azoles; Candidiasis; Caspofungin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Echinocandins; Fluconazole; Humans; In Vitro Techniques; Lipopeptides; Lipoproteins; Micafungin; Mycoses; Peptides, Cyclic; Pyrimidines; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Triazoles; Voriconazole

The emergence of resistance and changes in the spectrum of Candida infections have led to an increased interest in susceptibility testing of antifungal drugs. Such testing may be particularly useful in patients with invasive candidiasis who have been previously treated with azole antifungals, those whose infections are not responding to treatment, and those with infections caused by non-albicans species of Candida. The choice of a specific antifungal depends on the clinical status of the patient, the relative toxicity and efficacy of the drug in the given patient population, the infecting species and antifungal susceptibility of the isolate, and the patient's prior exposure to antifungal agents. Infectious Diseases Society of America recommendations for the initial management of candidemia and acute disseminated candidiasis include an azole, caspofungin, amphotericin B (AmB), or a combination of fluconazole plus AmB. Caspofungin and voriconazole show good activity against most Candida species and may be good alternatives for patients with Candida glabrata and Candida krusei infections and for those with relapsing infections.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Drug Resistance, Fungal; Echinocandins; Fluconazole; Health Status; Humans; Lipopeptides; Peptides, Cyclic; Pyrimidines; Risk Factors; Thiazoles; Treatment Outcome; Triazoles; United States; Voriconazole

Amphotericin B resistance among isolates of Candida lusitaniae has distinguished it among Candida species. Because no comprehensive review has been published recently, we provide a case report and a literature review of C. lusitaniae infection to update and better characterize the illness in the era of azole availability and standardized methodologies for antifungal susceptibility testing. C. lusitaniae infection in the 55 cases surveyed in this review occurred in relatively young patients (median age, 44 years). Fungemia was found in 80% of patients. Other infection syndromes, including peritonitis, meningitis, and urinary tract infection, were much less common. Three-fourths of the patients had serious underlying medical conditions. Despite the presence of fungemia and predisposing comorbidities, death due to C. lusitaniae infection was uncommon among treated patients (5.00%). Moreover, in vitro susceptibility testing results for amphotericin B did not appear to predict patient outcome in this survey.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cell Culture Techniques; Child; Child, Preschool; Drug Resistance, Microbial; Female; Fluconazole; Humans; Infant; Infant, Newborn; Male; Middle Aged; Treatment Outcome

The antifungal agents most frequently used in prophylaxis and treatment are amphotericin B (and its new lipid forms) and azoles such as fluconazole, itraconazole, and more recently voriconazole. This review assesses the role of itraconazole in paediatric haematology/oncology practice. Its broader spectrum of activity and availability in oral and intravenous forms allow a flexible approach in the management of fungal infections.

Topics: Absorption; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Child, Preschool; Cost-Benefit Analysis; Humans; Itraconazole; Mycoses

Despite significant advances in the management of immunosuppressed patients, invasive fungal infections remain an important life-threatening complication. In the last decade several new antifungal agents, including compounds in pre-existing classes (new generation of triazoles, polyenes in lipid formulations) and novel classes of antifungals with a unique mechanism of action (echinocandins), have been introduced in clinical practice. Ongoing and future studies will determine their exact role in the management of different mycoses. The acceleration of antifungal drug discovery offers promise for the management of these difficult to treat opportunistic infections.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Candidiasis; Deoxycholic Acid; Drug Combinations; Echinocandins; Fungal Proteins; Humans; Immunocompromised Host; Mycoses; Peptides; Peptides, Cyclic; Phosphatidylcholines; Phosphatidylglycerols; Triazoles

Candida albicans endocarditis occurs mostly in patients with congenital heart disease; open heart surgery is the greatest predisposing factor. We report on a child with truncus arteriosus communis and a large Candida vegetation within the prosthetic pulmonary valve, causing severe right ventricular outflow tract obstruction. Treatment was performed successfully by surgery and administration of liposomal amphotericin B (AmBisome) and 5-flucytosine.

Topics: Amphotericin B; Bacteria; Candida albicans; Candidiasis; Child; Endocarditis; Fungi; Humans; Male

Invasive bacterial and candidal infections are known to involve the retina, but the natural history of the retinal lesions and the utility of ophthalmologic consultation in the critical care setting as a diagnostic tool are not well understood. We 1) performed weekly funduscopic examinations on 77 medical and surgical patients in intensive care units (ICUs), 2) analyzed results of serial ocular examinations in 180 non-neutropenic patients with candidemia, and 3) reviewed the English literature on the association of retinal lesions with disseminated bacterial or candidal infection (DBCI). We found that 15 (19%) of the ICU patients had retinal lesions consistent with DBCI. Of these 15, 1 had clearly sepsis-related retinal lesions, while 13 (87%) had 1 or more systemic disease that could have explained their retinal findings (6 diabetic retinopathy; 2 human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) retinopathy; 2 hypertensive retinopathy; 1 hemolytic uremic syndrome, and 1 leukemia). Multivariate analysis revealed that systemic disease (odds ratio 8.37, 95% confidence intervals: 3.24-21.56) independently correlated with the presence of retinal lesions while DBCI, trauma, hyperalimentation, and transfusion of blood products were not independently predictive in any analysis. Twenty of the 180 (15%) candidemic patients had retinal lesions. Two (1%) had classic 3-dimensional white lesions with vitreal extension, and 5 (2.7%) had chorioretinal lesions without vitreal haziness. Notably, 10% of patients had superficial retinal hemorrhages and/or cotton wool spots that could have been due to either candidemia or a systemic disease (diabetes, hypertension, renal failure, closed head trauma). Concurrent bacteremia occurred in 3 of the 27 patients with eye lesions. Retinal lesions resolved in a mean of 33 days. None of the patients had symptoms at the time of the retinal finding. We found 3 studies that prospectively assessed retinal lesions in bacteremic patients. The frequency of retinal lesions in these series varied from 12% to 26%, with the most common lesions being cotton wool spots followed by superficial retinal hemorrhages. White-centered hemorrhages were seen in about 15% +/- 2 of bacteremic patients. Five studies prospectively evaluated candidemic patients for Candida endophthalmitis. These studies observed rates from 0% to 78% for lesions consistent with candidal endophthalmitis. Most studies performed recently found tha

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Corynebacterium Infections; Female; Fluconazole; Humans; Male; Middle Aged; Prospective Studies; Retinal Diseases; Severity of Illness Index; Staphylococcal Infections

Candida species rarely cause spondylodiscitis. During 3 y, 3 cases of vertebral osteomyelitis due to Candida spp. (Candida albicans and Candida tropicalis) were diagnosed, 2 of which were associated with a spinal epidural abscess.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Discitis; Female; Fluconazole; Follow-Up Studies; Fungemia; Humans; Lumbar Vertebrae; Magnetic Resonance Imaging; Osteomyelitis; Risk Assessment; Severity of Illness Index; Treatment Outcome

This article presents actual major problem about a steady increase in frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. However, there still remains much uncertainty regarding the best methods for establishing the diagnosis of most IFIs. An international consensus, that defining opportunistic IFIs proposed three levels of probability: "proven", "probable", and "possible". Practising physicians approach this uncertainty by prophylaxis and antifungal empirical therapy. Unfortunately, up to now we dispose only few antifungals compounds and all have narrow of therapeutic windows. This article reviews the therapeutic options in chemoprevention and antifungal therapy. Fluconazole and itraconazole are the first durable alternatives to polyenes in chemoprophylaxis. However their use remains controversial as debate continues over both their effectiveness and their potential to select out resistant Candida sp. Amphotericin B is the "gold" standard for the treatment both empirical and proven IFIs, but this drug is frequently associated with severe nephrotoxicity. The lipid formulations of amphotericin B enable higher dosages to be administrated with lower incidences of side effects but its effectiveness is not sufficient. It is to be hoped that rationally designed clinical trials with the new compounds, such as for example echinocandins will lead to improved prevention and treatment of IFIs.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Drug Administration Schedule; Fluconazole; Humans; Immunocompromised Host; Preventive Health Services

The echinocandins are large lipopeptide molecules that are inhibitors of beta-(1,3)-glucan synthesis, an action that damages fungal cell walls. In vitro and in vivo, the echinocandins are rapidly fungicidal against most Candida spp and fungistatic against Aspergillus spp. They are not active at clinically relevant concentrations against Zygomycetes, Cryptococcus neoformans, or Fusarium spp. No drug target is present in mammalian cells. The first of the class to be licensed was caspofungin, for refractory invasive aspergillosis (about 40% response rate) and the second was micafungin. Adverse events are generally mild, including (for caspofungin) local phlebitis, fever, abnormal liver function tests, and mild haemolysis. Poor absorption after oral administration limits use to the intravenous route. Dosing is once daily and drug interactions are few. The echinocandins are widely distributed in the body, and are metabolised by the liver. Results of studies of caspofungin in candidaemia and invasive candidiasis suggest equivalent efficacy to amphotericin B, with substantially fewer toxic effects. Absence of antagonism in combination with other antifungal drugs suggests that combination antifungal therapy could become a general feature of the echinocandins, particularly for invasive aspergillosis.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Caspofungin; Clinical Trials as Topic; Echinocandins; Fungal Proteins; Humans; Lipopeptides; Lipoproteins; Micafungin; Peptides; Peptides, Cyclic; Treatment Outcome

A case is reported of isolated native tricuspid calve Candida parapsilosis endocarditis (INTVCE) in a male patient with no history of drug abuse or heart disease. The patient had received hyperalimentation and antibiotics for four months via a central venous catheter after abdominal surgery. He underwent successful treatment with tricuspid valve debridement, liposomal amphotericin (AmBisome) and fluconazole, and remained without relapse during an eight-year follow up. A literature review of 12 similar cases (including the present patient) without history of drug abuse or heart disease, dating from 1970, is included.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Debridement; Echocardiography; Endocarditis; Fluconazole; Humans; Male; Middle Aged; Parenteral Nutrition, Total; Substance-Related Disorders; Tomography, X-Ray Computed; Tricuspid Valve

Candida is a leading cause of late onset infection (> 3 days of age) in the premature infant. Therefore, decisions about the diagnosis and management of infections caused by Candida are commonplace in the neonatal intensive care unit. Despite this fact, there are few comparative trials about treatment of neonatal Candida infections to guide the practitioner. New antifungals have been developed in the past decade and some clinical experience has been reported that can be used to guide the treatment of infants with serious Candida infections. This article reviews recent pertinent data with regard to dosing guidelines, efficacy, and toxicities of available systemic antifungal agents in the newborn.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Cross Infection; Echinocandins; Fluconazole; Flucytosine; Fungal Proteins; Fungemia; Humans; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Ketoconazole; Lipopeptides; Peptides; Peptides, Cyclic; Pyrimidines; Triazoles; Voriconazole

Candida species are a common cause of urinary tract infection in newborns requiring intensive care. Renal candidiasis is frequently associated with these urinary tract infections and is manifest by "fungus balls" or renal parenchymal infiltration. Candidal urinary tract infections in high-risk newborns are often associated with candidemia, thereby warranting systemic antifungal therapy. Sonography is useful in diagnosing renal candidiasis, obstruction from "fungus balls," and abscesses. The sonographic appearance of "fungus balls" may persist long after clinical resolution of Candida infection in neonates and should not affect duration of antifungal therapy. Amphotericin B is currently the drug of choice for neonates with renal candidiasis and candidal urinary tract infection. Surgical management should be reserved for decompression of obstructive candidiasis and drainage of abscesses.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cross Infection; Drainage; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Kidney Diseases; Urinary Tract Infections

Invasive candidiasis is a feared infection with mortality similar to that of septic shock (40-60%). Improved knowledge of its pathophysiology and the availability of new compounds for antifungal therapy and prophylaxis have contributed to improving the prognosis of severe candidal infections among immunosuppressed patients at the possible cost of the emergence of non-albicans strains of candida with lower susceptibility to azoles. This review focuses on the management of invasive deep-seated candidiasis in critically ill, non-immunocompromised patients. We discuss antifungal use, indications, potential benefit, and main secondary effects. Prevention strategies include pre-emptive antifungal therapy and azole-based prophylaxis. For patients at lower initial risk, pre-emptive therapy should be based on a management strategy that takes into account the presence of definite risk factors and the dynamics of candida colonisation. Among critically ill patients, azole prophylaxis is effective and is not associated with acquisition of resistance; it must be restricted to highly selected groups of patients at high risk only.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candidiasis; Clinical Trials as Topic; Critical Illness; Humans; Immunocompetence; Nystatin; Practice Guidelines as Topic

Despite significant advances in the diagnosis, prevention, and treatment of fungal infection in transplant recipients, this infection complication remains a major cause of morbidity and mortality. Our understanding of the pathogenesis of the different fungal microorganisms has enabled us to identify patients at risk for such infections. While Candida infection remains a major complication in patients with intra-abdominal solid organ transplantations in which the bowel is surgically manipulated, Aspergillus infection remains the main fungal complication in lung transplantation recipients. The incidence of all types of fungal infection remains around 5-10%, while mortality following Aspergillus infection remains around 70%. Suppression of Candida growth at the time of surgical manipulation of the bowel should be the mainstay of prevention of this infection in intra-abdominal organ transplantation. Fluconazole is effective and relatively safe at 100-400 mg daily for the first 1-3 months post-liver transplantation. Prevention strategies toward Aspergillus infections remain elusive, but a number of manipulations, such as inhaled liposomal preparations post-organ transplantation or the preemptive use or universal prophylaxis of itraconazole are being validated. The next step is to determine the clinical value of molecular diagnostic techniques for the identification and preemptive therapy of patients at risk for the variety fungal infections.

Topics: Amphotericin B; Antifungal Agents; Basement Membrane; Candida; Candidiasis; Cytomegalovirus Infections; Fluconazole; Humans; Mycoses; Organ Transplantation; Risk Factors

The increase in the incidence of fungal infections and the emergence of resistance call for the development of techniques for measuring in vitro antifungal susceptibility that are useful for predicting clinical outcome in patients suffering from these infections. In the past, the lack of standardized testing techniques led to poor intra- and interlaboratory reproducibility. Recently, the National Committee for Clinical Laboratory Standards (NCCLS) has developed a reference method for antifungal susceptibility testing, document M27A. This document is a necessary and important step towards the standardization of antifungal susceptibility testing, which has important implications in the analysis of clinical and microbiological data. This article provides a comprehensive review of studies correlating in vitro antifungal susceptibility testing and clinical outcome. In general, it is possible to predict the therapeutic outcome, especially in HIV infected patients with oropharyngeal candidiasis treated with fluconazole. However, in other more heterogeneous groups of patients it is more difficult to correlate the in vitro and in vivo data.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cryptococcosis; Fluconazole; Humans; Itraconazole; Microbial Sensitivity Tests

Candida infections are increasingly being recognized as a major cause of septicaemia in neonatal intensive care units, and are associated with high morbidity (25%) and mortality (25-54%). Low birth weight pre-term infants are especially vulnerable to this devastating disease. The most frequently encountered fungal infections are caused by Candida albicans, Candida parapsilosis and, rarely, by Candida tropicalis. Amphotericin B (with or without flucytosine) is the treatment of choice for Candida infections in neonates. Conventional amphotericin B use is often limited by its severe side effects, although these tend to be fewer in neonates than in adults. Possible alternatives to amphotericin B include triazoles (such as fluconazole) and lipid preparations of amphotericin B. Liposomal encapsulation of amphotericin B has been shown to decrease the toxicity of the drug while maintaining its antifungal activity. The liposomal formulation AmBisome has proved to be effective in the treatment of severe fungal infections in adult and paediatric immunocompromised patients who fail to respond to conventional amphotericin B. The experience with AmBisome in the treatment of fungal infections in neonates is limited, and the drug has been used mainly in infants either failing conventional amphotericin B or having intolerable toxicity. Pharmacokinetic studies have not yet been performed in neonates. Three uncontrolled studies published between 1997 and 1998 on AmBisome (dose range 1-7 mg/kg/day) in the treatment of neonatal candidosis revealed that the drug was effective and safe. New information is accumulating on the safe use of high-dose AmBisome (5-7 mg/kg/day) in very low birth weight infants, and successful use of the drug as first-line therapy of neonatal candidosis. These promising results suggest a potential role for AmBisome as an additional first-line treatment of systemic candidosis in neonates.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Decision Making; Disease Management; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Liposomes

Risk factors and treatment strategies for systemic candidal infections in the intensive care unit (ICU) are discussed. The past two decades have seen a dramatic increase in the frequency of infections caused by Candida species. Risk factors associated with candidemia include treatment with multiple antimicrobials for extended periods, presence of central venous catheters, total parenteral nutrition, colonization by Candida species, abdominal surgery, prolonged stay in the ICU, and compromised immune status. Since the 1960s, conventional amphotericin B has been the primary treatment option for fungal infections. Although effective, amphotericin B has extensive toxicity. Three lipid-based formulations of amphotericin B have been developed in an attempt to decrease nephrotoxicity and improve drug delivery. Practitioners have also been offered alternatives by the introduction of less toxic azole antifungals, such as ketoconazole, fluconazole, and itraconazole; however, their widespread use has resulted in other problems, such as the selection of resistant isolates. There is controversy concerning fluconazole's effectiveness. In the treatment of systemic candidal infections, especially in critically ill patients. Clinical trials do not support the prophylactic or empirical use of fluconazole in the ICU. Treating patients who have no microbiological evidence of infection provides no therapeutic benefit and shifts the fungal flora to noncandidal strains that are more resistant to fluconazole. Patients in ICUs are often susceptible to systemic candidal infection. Preemptive therapy with fluconazole may reduce mortality in high-risk patients. Fluconazole and amphotericin B appear equally effective in treating established systemic candidal infections.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Candidiasis; Cross Infection; Drug Resistance, Microbial; Fluconazole; Humans; Intensive Care Units; Risk Factors

Candida albicans and related species pathogenic for man become resistant to antifungal agents, in particular triazole compounds, by expression of efflux pumps that reduce drug accumulation, alteration of the structure or concentration of antifungal target proteins, and alteration of membrane sterol composition. The clinical consequences of antifungal resistance can be seen in treatment failures in patients and in changes in the prevalences of Candida species causing disease. These effects were seen unequivocally in HIV-infected patients with oropharyngeal candida infections, but their incidence has decreased dramatically with the introduction of highly active antiretroviral therapy. The evidence for similar emergence of antifungal-resistant yeast strains and species in other types of candida infections is confounded by non-standardised susceptibility testing methods and definitions of a resistant fungal isolate. Recent large-scale surveys of yeasts isolated from blood cultures, based on standardised methodology and resistance definitions, do not support the view that antifungal resistance in pathogenic yeasts constitutes a significant or growing therapeutic problem.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candidiasis; Cytochrome P-450 Enzyme System; Drug Resistance, Fungal; Flucytosine; Fungemia; Humans; Microbial Sensitivity Tests; Oxidoreductases; Sterol 14-Demethylase; Triazoles

The management of superficial fungal infections differs significantly from the management of systemic fungal infections. Most superficial infections are treated with topical antifungal agents, the choice of agent being determined by the site and extent of the infection and by the causative organism, which is usually readily identifiable. One exception is onychomycosis, which usually requires treatment with systemically available antifungals; the accumulation of terbinafine and itraconazole in keratinous tissues makes them ideal agents for the treatment of onychomycosis. Oral candidiasis in immunocompromised patients also requires systemic treatment; oral fluconazole and itraconazole oral solution are highly effective in this setting. Systemic fungal infections are difficult to diagnose and are usually managed with prophylaxis or empirical therapy. Fluconazole and itraconazole are widely used in chemoprophylaxis because of their favourable oral bioavailability and safety profiles. In empirical therapy, lipid-associated formulations of amphotericin-B and intravenous itraconazole are safer than, and at least as effective as, conventional amphotericin-B (the former gold standard). The high acquisition costs of the lipid-associated formulations of amphotericin-B have limited their use.

Topics: Administration, Oral; Administration, Topical; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Chemistry, Pharmaceutical; Dermatomycoses; Fluconazole; Humans; Intestinal Absorption; Itraconazole; Onychomycosis

Not only have the systemic mycoses clearly increased in number but also mycoses of the skin are more common than presumed in the past. Today onychomycosis is found in up to 10% of human beings. Onychomycosis can compromise quality of life markedly. Common tinea pedis is one of the most important risk factors for erysipelas of the lower legs. The clinical presentation of oral candidosis in HIV-infected patients is changing; Candida dubliniensis has been identified as another important causative microorganism. Onychomycosis today in most cases can be cured using terbinafine or itraconazole. When choosing the ideal drug in a given case, both the benefit risk ratio and the benefit cost ratio have to be taken into account. Liposomally encapsulated amphotericin B represents a major breakthrough in the treatment of systemic mycoses or fever of unknown origin. The same applies to liposomally encapsulated econazole with respect to tinea pedis. In regard to the pathogenesis of Candida infections the family of secreted aspartic proteinases plays a major role as a virulence factor and possible future target for antimycotic treatment.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Aspartic Acid Endopeptidases; Axilla; Candida albicans; Candidiasis; Candidiasis, Cutaneous; Candidiasis, Oral; Candidiasis, Vulvovaginal; Case-Control Studies; Child; Clinical Trials as Topic; Dermatomycoses; Female; Humans; Liposomes; Microscopy, Immunoelectron; Multicenter Studies as Topic; Multivariate Analysis; Naphthalenes; Onychomycosis; Practice Guidelines as Topic; Prospective Studies; Risk Factors; Terbinafine; Tinea; Tinea Pedis; Trichophyton

To report a case of explosive fungal endophthalmitis after penetrating keratoplasty and to review additional published and unpublished cases to consider possible strategies for prevention.. Records of this patient with postkeratoplasty candidal endophthalmitis and previously reported cases of postkeratoplasty candidal endophthalmitis were reviewed. Additional information of 26 unpublished cases was obtained from the Eye Bank Association of America.. After standard keratoplasty, the patient developed precipitous endophthalmitis on the second postoperative day. Abundant contamination with Candida was found in the residual donor corneoscleral rim, and Candida albicans was isolated from the aqueous humor of the recipient. Despite therapy with local antimicrobial agents, intraocular amphotericin B, and systemic fluconazole, the patient had a poor outcome with hand-motion visual acuity. Of the 44 collected cases of postkeratoplasty candidal endophthalmitis, 40 (91%) had the same organism cultured from the donor rim or medium. Forty-three donor corneas had been preserved in cold storage medium at 4 degrees C. Of 15 cases in which the outcome was available, 9 (60%) resulted in visual acuity of 20/200 or worse.. Case reports confirm the occurrence of donor-to-host transmission of postkeratoplasty candidal endophthalmitis. Despite the low reported incidence, the poor prognosis of the affected eye in the ajority of these cases suggests the need for antifungal supplementation of cold preservation media and other preventative strategies.

Topics: Aged; Amphotericin B; Aqueous Humor; Candida albicans; Candidiasis; Combined Modality Therapy; Cornea; Endophthalmitis; Eye Infections, Fungal; Female; Humans; Keratoplasty, Penetrating; Male; Middle Aged; Reoperation; Tissue Donors

Invasive fungal infections remain a common cause of morbidity and mortality among patients with leukemia who become further compromised by neutropenia. Candida and Aspergillus spp account for the vast majority of these infections, but other, less commonly recognized fungi can cause life-threatening infection in these hosts as well. The earlier, more limited antifungal armamentarium of ketoconazole, flucytosine, and amphotericin B has been substantially augmented by the availability of fluconazole, itraconazole, and the lipid-associated amphotericin formulations. Intense clinical study has focused on the use of these agents in empiric treatment, treatment of suspected or proven infection, and prophylaxis. Recognition of the limitations of antifungal therapy in the neutropenic host has led to evaluation of the adjunctive role of immunotherapy.

Topics: Amphotericin B; Aspergillosis; Azoles; Candidiasis; Fluconazole; Humans; Immunotherapy; Leukemia; Mycoses; Neutropenia

During the last decade the incidence of deep mycotic infections has continued to increase dramatically. This new epidemiological feature is mostly due to the expanding population of at risk subjects submitted to intensive and protracted immunosupression. Amphotericin B has a broad spectrum and has remained the drug of choice for these life threatening invasive fungal infections. However adverse events, particularly renal insufficiency, are limiting factors in achieving an effective dose. Since the 1990s the number of oral and parenteral antifungal agents has significantly increased. The use of phospholipid carriers for amphotericin B or cyclodextrine for triazoles improved safety profil and/or pharmacokinetics. New families of drugs with a new target in the fungal cell are under clinical investigation and should be soon available. Comparative studies, consensus on diagnosis criteria and practice guidelines for the treatment of fungal infections will contribute to a better management of the patients and optimize the use of antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Fluconazole; Flucytosine; Humans; Itraconazole; Lung Diseases, Fungal; Mycoses; Time Factors

Amphotericin B (AmB) resistance in Candida spp. is very rare. Three cases of fungemia, due to amphotericin B-resistant Candida spp. in pediatric patients after previous neurosurgery for brain tumors, are reported. The Candida strains - one C. guillermondii, one C. lusitaniae, and one C. parapsilosis - showed minimum inhibitory concentrations (MICs) to AmB of 2-4 microg/ml. Two of the three patients had been pretreated with AmB for 5-11 days. All three patients were successfully treated with intravenous fluconazole (6-10 mg/kg per day) for 16-28 days, and all survived. Despite AmB resistance in Candida spp. being very rare, C. lusitaniae, C. guillermondii, and C. parapsilosis isolates in documented infections should be tested for AmB resistance, mainly in patients not responding to therapy with AmB.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Brain Neoplasms; Candida; Candidiasis; Catheterization, Central Venous; Child; Child, Preschool; Craniotomy; Cross Infection; Drug Resistance, Microbial; Equipment Contamination; Fluconazole; Fungemia; Hospitals, Pediatric; Humans; Microbial Sensitivity Tests; Postoperative Complications; Slovakia; Species Specificity; Ventriculoperitoneal Shunt

The incidence of bloodstream infections caused by Candida species is rising. Few published studies have compared the efficacy of fluconazole with that of amphotericin B. We performed a meta-analysis of the prospective studies that compared fluconazole and amphotericin B for the treatment of candidaemia in adults. Data on total mortality, candidaemia-attributable mortality, efficacy, microbiological failure, and toxicity were extracted from eligible studies. All studies appeared homogeneous with respect to the outcome measures. Most patients were at relatively low risk for death as evidenced by the low average physiologic score and the lack of intense immunosuppression. The odds ratios (OR) of treatment with amphotericin B versus fluconazole and 95% confidence intervals (CI) were as follows: total mortality (OR, 1.06; CI, 0.89-1.25), candidaemia-attributable mortality (OR, 1.0; CI, 0.70-1.45), clinical response (OR, 1.14; CI, 0.93-1.39) and microbiological failure according to all Candida species (OR, 0.99; CI, 0.78-1.26). A trend favouring amphotericin B was seen in mycological eradication of non-albicans Candida species (OR, 0.70; CI, 0.47-1.06). Finally, amphotericin B was more toxic than fluconazole (OR, 2.94; CI, 2.14-4.4). In conclusion, fluconazole is as efficacious and less toxic than amphotericin B in stable, not severely immunosuppressed candidaemic patients at low risk for death. However, fluconazole may be less effective than amphotericin B in candidaemias caused by some non-albicans Candida species.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Clinical Trials as Topic; Fluconazole; Fungemia; Humans; Odds Ratio; Treatment Failure

A systematic review of randomized clinical trials published between 1966 and April 2000 was undertaken to determine the strength of evidence for the effectiveness of antifungal drugs (nystatin, clotrimazole, amphotericin B, fluconazole, ketoconazole, and itraconazole) to prevent and treat oral candidiasis in human immunodeficiency virus-positive patients.. An automated database search identified 366 articles. Six met inclusion and exclusion criteria with respect to prophylaxis; 12 met criteria for treatment of oral candidiasis.. The evidence for the prophylactic efficacy of fluconazole is good, although insufficient to draw conclusions about the other antifungals. Evidence for treatment effectiveness is insufficient for amphotericin B but good for nystatin, clotrimazole, fluconazole, ketoconazole, and itraconazole.. Suggestions for strengthening the evidence base include the following: use of larger, more well-defined groups; control for immunologic status, viral load, history of oral candidiasis, past exposure to antifungals, baseline oral Candida carriage, drug interactions, and antiretroviral therapy; and consistent use of compliance monitors, fungal speciation, and susceptibility testing.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candidiasis; Candidiasis, Oral; Clotrimazole; Databases as Topic; Fluconazole; HIV Seropositivity; Humans; Itraconazole; Ketoconazole; Nystatin; Oropharynx; Pharyngeal Diseases; Randomized Controlled Trials as Topic; Research Design; Statistics as Topic; Treatment Outcome

Antibody-based therapeutics have come of age, with advances in the genetic engineering of recombinant antibodies allowing application of a growing knowledge of the immunopathology of diseases to the development of novel drugs. For infections such as systemic candidiasis, which still have a mortality of 40 to 50%, antifungal antibodies could provide long-awaited novel therapies for use in combination with antifungal agents. They may also evolve into safe, broad-spectrum agents for prophylaxis in high-risk immunocompromised patients. Mycograb, a human genetically recombinant antibody against heat shock protein 90 (hsp90), has just started trials in patients with systemic candidiasis.

Topics: Amphotericin B; Animals; Antibodies, Fungal; Antibodies, Monoclonal; Candidiasis; Drug Therapy, Combination; HSP90 Heat-Shock Proteins; Humans; Membrane Glycoproteins; Mice; Recombinant Proteins

The implantable cardioverter-defibrillator (ICD) represents an important advance in the treatment of ventricular arrhythmias, but infection has remained a serious complication of device implantation. Fungal infections associated with these devices are uncommon, with only 4 cases previously reported. We describe a case of ICD-associated endocarditis caused by Candida albicans that was successfully treated with complete device explantation and prolonged antifungal therapy, and we review the features of ICD-related fungal infections.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Defibrillators, Implantable; Endocarditis; Humans; Male; Middle Aged; Prosthesis-Related Infections; Tachycardia, Ventricular

Opportunistic mycoses have emerged as important causes for morbidity and mortality in pediatric cancer patients, particularly in those with intensively treated hematological malignancies, allogeneic hematopoetic stem cell transplantation, and aplastic anemia. The incidence of invasive fungal infections in these settings may range from 10 to 25 % despite empirical antifungal therapy with an overall case fatality rate of up to 50 and 75 % depending on the organism. Preventive interventions are thus warranted, including but not limited to chemoprophylaxis with antifungal agents. Effective chemoprophylaxis of invasive Candida infections with a long-term benefit for overall survival has been demonstrated in patients with allogeneic bone marrow transplantation. However, its benefit in other high-risk populations is less well established, and a clearly effective approach to chemoprophylaxis for invasive Aspergillus infections has not been documented in appropriately designed clinical trials. This article reviews epidemiology and current approaches to chemoprophylaxis of opportunistic invasive fungal infections in children and adolescents with cancer and/or stem cell transplantation, and provides evidence-based guidelines for indications and modalities of antifungal prophylaxis and antifungal infection control measures in this population.

Topics: Administration, Oral; Adolescent; Adult; Age Factors; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Child; Child, Preschool; Cohort Studies; Double-Blind Method; Fluconazole; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Infant, Newborn; Itraconazole; Mycoses; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic; Respiratory Therapy; Risk Factors; Time Factors

Efforts at preventing and treating fungal infection in hematopoietic stem cell transplant (HSCT) recipients must take into account the types of infections likely to be encountered during the different risk periods in hosts with different underlying risks. Given the emergence of molds as prevalent pathogens and the long duration of risk in allogeneic HSCT recipients, optimal antifungal prophylaxis would consist of treatment that can be given over a prolonged period and that would provide both anti-Candida and anti-Aspergillus activity. Optimal empiric therapy would consist of a broad-spectrum agent in the absence of more sensitive and specific methods for microbial diagnosis. Fluconazole (Diflucan) is currently the standard prophylactic agent for candidiasis, although mold-active agents and alternative strategies for polyene administration are being investigated. The gold standardfor empiric therapy is currently a polyene antifungal, yet an increased appreciation for amphotericin B-resistant yeasts and molds, and less toxic mold-active alternatives, might lead to the use of other compounds in the future. The recent development of multiple alternatives emphasizes our need to establish treatment algorithms that consider both the likely pathogens and potential toxicities.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Aspergillosis; Candidiasis; Fluconazole; Hematopoietic Stem Cell Transplantation; Humans; Itraconazole; Neutropenia; Opportunistic Infections; Risk Factors

To present a case describing Candida lusitaniae candidemia in an immunocompetent patient successfully treated with fluconazole antifungal therapy. Time-kill studies of the C. lusitaniae isolate using amphotericin B, and an extensive review of the literature are also presented.. A 52-year-old immunocompetent Latin-American woman was admitted to the special care unit with severe sepsis. Her recent medical history included an exploratory laparotomy for gallstone pancreatitis, requiring cholecystectomy, segmental sigmoid colectomy, drainage of peritoneal abscesses, and a colostomy. In addition, the patient required a central venous catheter (CVC) placement for prolonged broad-spectrum antibiotic therapy and total parenteral nutrition therapy. Yeast was isolated from the abdominal abscess and blood cultures obtained on day 1, and from the catheter tip on day 5. The woman received initial empiric antifungal therapy with fluconazole, which was later changed to amphotericin B. After the yeast was identified as C. lusitaniae on day 8, this was changed to fluconazole for the duration of therapy. C. lusitaniae was not present in blood cultures taken two weeks after the CVC was removed, and the cultures remained negative thereafter. After a prolonged hospitalization, the patient was discharged home.. Disseminated infections with C. lusitaniae usually occur in immunocompromised patients, although isolated reports of C. lusitaniae infections in immunocompetent patients have been described. Therapeutic challenges of C. lusitaniae treatment include its primary resistance to amphotericin B and species misidentification. Isolates recovered from our patient were submitted for fungus time--kill studies that suggested unique susceptibility patterns to amphotericin B, indicating a trend toward resistance.. Based on variable susceptibility patterns of C. lusitaniae to amphotercin B and flucytosine, fluconazole is an appropriate choice as first-line therapy for C. lusitaniae candidemia.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Catheters, Indwelling; Equipment Contamination; Female; Fluconazole; Humans; Middle Aged; Risk Factors

Amphotericin B (AmB) is considered the drug of choice for the treatment of systemic fungal infections. Nephrotoxicity is a major complication associated with its use, and appears to be related to higher cumulative doses, diuretic use, abnormal serum creatinine at baseline, and the use of concomitant nephrotoxic drugs. The two major hypotheses for the pathogenesis of AmB-related nephrotoxicity are direct effects of the drug on epithelial cell membranes and vasoconstriction. During the last few years, some randomized trials have tested different strategies to reduce AmB-induced renal toxicity. These strategies include sodium supplementation, low-dose dopamine, slower infusion rates, the administration of AmB in lipid emulsions, and in lipid formulations. The results of these trials showed that the lipid formulations of AmB significantly reduce nephrotoxicity. Unfortunately, these agents are costly, restricting their use to patients with a high risk of developing renal failure.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Creatinine; Drug Compounding; Humans; Incidence; Intensive Care Units; Kidney Tubules; Renal Insufficiency; Risk Factors

Infections remain a major complication of hematopoietic stem cell transplantation, with recent trends indicating that fungal pathogens have become one of the most common causes of death. Attention has turned to the use of prophylactic antifungal medications to prevent infection with both Candida and Aspergillus species. Recent studies, which are reviewed within, indicate success in preventing infections caused by azole-susceptible Candida species, accompanied by improved transplant-related mortality rates in high-risk patients. Further studies are necessary to develop strategies to prevent infection with Aspergillus species.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Fluconazole; Hematopoietic Stem Cell Transplantation; Humans; Itraconazole

Hematogenous candidemia is an increasingly frequent problem among patients who are immunosuppressed, receiving parenteral nutrition and/or antibiotics, or who have invasive medical devices such as indwelling catheters. In Brazil, Candida albicans was responsible for 53/145 (37%) of candidemia in 6 different tertiary care hospitals. The most common non-albicans species were C. parasilosis (25%), C. tropicalis (24%), C. rugosa (5%) and C. glabrata (4%). The main risk factors for infection were antibiotic use and the presence of a central venous catheter. The main risk factors for mortality were patient age (older patients at risk) and not removing the catheter. Because of the great number of non-albicans species and varied degrees of antifungal drug sensitivity, laboratory identification and sensitivity testing is very important. All patients with documented candidemia should be treated. Drugs to be used are amphotericin B and/or fluconazole. Fluconazole resistance is not yet a problem in Brazil, perhaps because it is rarely used as prophylaxis due to its high cost. Intravenous catheters should be removed immediately if the patient has a short term catheter, or if the patient is clinically unstable due to the infection and has a long term catheter in place.

Topics: Amphotericin B; Antifungal Agents; Brazil; Candida; Candidiasis; Cross Infection; Fluconazole; Fungemia; Humans; Risk Factors

Topics: Amphotericin B; Candidiasis; Central Nervous System Diseases; Cross Infection; Drug Therapy, Combination; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Prognosis

RISING INCIDENCE: In the past two decades, systemic fungal infections, essentially invasive candidiasis, but also invasive aspergillosis, has increased substantially. Despite the currently available antifungal drugs, amphotericin B (AmB), azole compounds (fluconazole or FLU, itraconazole or ITR), these infections are associated with significant morbidity and mortality. AmB remains the drug of choice for treatment of most fungal diseases because of its broad spectrum and potent fungicidal activity, but significant side effects limit its clinical utility. The azole antifungal agents are easier to take, less toxic than AmB, but their use is limited by multiazole-resistant strains. NEW ANTIFUNGAL AGENTS: Lipid formulations have recently attracted much attention due to a significantly lower toxicity: this concerns lipid formulations of AmB and perhaps nystatin in the future. New triazoles (voriconazole, ravuconazole, posaconazole) have shown a wide spectrum of action including against azole-resistant isolates. A new class of antifungal agents, lipopeptides (MK-0991, LY303366, FK463), with an original mechanism of action are being developed. These new compounds are reported to possess a large fungicidal activity against most isolates including AmB and azole-resistant strains.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Drug Resistance, Microbial; Humans; Immunocompromised Host; Incidence; Nystatin; Risk Factors; Triazoles

The risk factors, therapy and outcome of ten cases of fungemia due to Candida krusei, appearing during the last 10 years in a single national cancer institution, are analyzed. Univariate analyses did not find any specific risk factors in comparison to 51 Candida albicans fungemias appearing at the same institution and with a similar antibiotic policy. Association with prior fluconazole prophylaxis was not confirmed because only one case appeared in a patient previously treated with fluconazole. However, attributable and crude mortality due to C. krusei fungemias was higher than for C. albicans fungemia. The authors review 172 C. krusei fungemias published within the last 10 years to compare with the incidence, therapy and outcome of C. krusei fungemia from our cancer institute.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; Female; Fluconazole; Fungemia; Humans; Incidence; Male; Middle Aged; Neoplasms; Risk Assessment; Treatment Outcome

Systemic fungal infections cause almost 25% of the infection-related deaths in leukaemic patients. Particularly those with prolonged neutropenia are at risk but mycoses also feature in critically ill intensive care patients and in individuals who are treated for solid tumours and AIDS, or who received an organ transplant. The spread of AIDS and the more aggressive cytotoxic chemotherapy in combination with an improved management of haemorrhages and bacterial infections in leukaemic and other cancer patients facilitated the occurrence of these invasive fungal infections. These life-threatening complications remain both difficult to diagnose and to treat and therefore carry a poor prognosis. For many years, the only realistic option to treat systemic infections was amphotericin B, whose administration was known to be associated with numerous adverse effects. Now less toxic formulations of amphotericin have become available for clinical use, as well as several new triazoles that appear to provide an effective and less toxic alternative for the treatment of certain fungal infections.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Fluconazole; Flucytosine; Fungemia; Histoplasmosis; Humans; Immunocompromised Host; Mycoses; Zygomycosis

Five clinical trials of the efficacy of amphotericin B colloidal dispersion (ABCD) primarily in patients unable to tolerate or failing treatment with conventional amphotericin B (CAB) were reviewed. A total of 572 patients were treated. Systemic candidal infections were identified in 107 evaluable patients and 239 in the intent-to-treat population. Seventy percent of the evaluable patients and 50% of the intent-to-treat patients achieved a complete or partial response. There were no significant differences either in response rates for different underlying causes or in response rates according to enrollment reason. The efficacy of ABCD at doses of 3-4 mg/kg/ day in disseminated candidiasis appears to be similar to that in studies using CAB. Renal and hepatic toxicity of ABCD is low.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Clinical Trials as Topic; Fungemia; Humans; Multicenter Studies as Topic; Treatment Outcome

The efficacy and safety of Amphotericin B Colloidal Dispersion (ABCD) have been investigated on 572 patients in five Phase I/II clinical trials. The patients were all selected to present a challenging test; having a fungal infection superimposed on severe illness. In 442 cases ABCD was used after amphotericin B, which had been withdrawn. One hundred and forty patients had pre-existing nephrotoxicity. Most patients received doses of 3-6 mg/kg/day of ABCD. Complete or partial recovery was reported in 149/260 (57.3%) patients evaluable for therapeutic response. Patients with Candida infection responded better than those with systemic aspergillosis showing 70.1% recovery vs. 48.8%. ABCD therapy made no difference to serum creatinine levels, even in patients with pre-existing renal failure, nor to liver function as measured by SGOT, alkaline phosphatase and total bilirubin levels in serum. Infusion-related adverse events were the most frequently reported side effects of ABCD. However these studies show clearly that ABCD can be administered safely to patients without the risks of renal toxicity, even when renal toxicity had already developed following therapy with conventional amphotericin B deoxycholate.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Humans; Treatment Outcome

We report a case of arthritis due to Candida (Torulopsis) glabrata in two different joints at different times in the same patient. The first episode of arthritis was situated in the right ankle and lasted more than 1 year before the patient agreed to the proposed treatment. Therapy with intravenous amphotericin B and oral fluconazole failed. A cure was achieved with weekly intra-articular administration of amphotericin B, which was continued for more than 20 weeks and combined with oral itraconazole. Several weeks later the patient developed Candida glabrata arthritis of the left knee while still taking itraconazole. Immediately, intravenous amphotericin B therapy was started and was successful. Because there were no previous invasive point manipulations or trauma, the infections were considered to be haematogenously disseminated. Chronic corticosteroid and repeated antibiotic therapy for infectious exacerbations of chronic obstructive pulmonary disease and alcohol abuse are the presumed risk factors in this otherwise immunocompetent patient.

Topics: Adult; Amphotericin B; Ankle Joint; Arthritis, Infectious; Candida; Candidiasis; Humans; Injections, Intra-Articular; Male; Radiography; Synovial Fluid

Recent findings on the epidemiology and treatment of funguria are reviewed. Funguria, or candiduria, is a common nosocomial condition and may develop as early as the first two weeks of hospitalization. Risk factors include antibacterial therapy, an indwelling urinary catheter, urologic procedures, female sex, diabetes, and immunosuppressive therapy. Candida albicans is the species most commonly isolated from the urine of infected patients. Spontaneous resolution of funguria is relatively infrequent. Furthermore, although nonpharmacologic measures, such as removing unnecessary antibacterials and changing or removing indwelling urinary catheters, may be beneficial, they are often inadequate without additional, pharmacologic therapy. The most serious complication of untreated asymptomatic funguria is candidemia. Bladder irrigations with amphotericin B have been the standard of therapy for many years; recently, the optimal concentration and method of irrigation (continuous versus intermittent) have been debated. Studies indicate that intravesical amphotericin B and oral fluconazole therapy are each effective in clearing funguria. Intravesical amphotericin B appears to act more rapidly; however, the effect of systemic fluconazole therapy often persists longer than that of amphotericin B irrigation, and oral therapy is more convenient and less expensive. Oral fluconazole appears to have a more delayed but more lasting effect on funguria than amphotericin B bladder irrigation. Studies are needed to determine whether intravesical amphotericin B still has a role in the treatment of funguria and to refine strategies involving fluconazole.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cross Infection; Female; Fluconazole; Humans; Male; Sex Factors; Urinary Catheterization; Urinary Tract Infections

Candida species is now being increasingly recognised as an important cause of endocarditis especially in immunocompromised patients. A case of Candida albicans endocarditis in a child with acute lymphoblastic leukemia (ALL) is reported. The child did not have a central venous catheter at any time. Treatment consisted of intravenous amphotericin B and fluconazole for 3 weeks followed by oral fluconazole for 2 weeks. No surgical resection was necessary. We highlight here the importance of echocardiography in the management of prolonged febrile neutropenia and discuss the dilemma of continuing chemotherapy in such patients.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Child, Preschool; Drug Therapy, Combination; Endocarditis; Fluconazole; Humans; Injections, Intravenous; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome

Amphotericin B (AmB) continues to be the mainstay of therapy for serious fungal infections, despite its relatively toxic side-effect profile. Lipid preparations of the medication have been marketed in the past few years in an attempt to reduce some of these side effects, especially nephrotoxicity. Although 6 cases of severe hypertension associated with the use of AmB deoxycholate have been reported in the literature, no cases of hypertension associated with a lipid-containing preparation of the medication have been reported. We report here the first case of severe hypertension associated with the infusion of AmB lipid complex (ABLC) in a patient with multiple intraperitoneal and urinary fungal pathogens. We also provide a brief review of the previously reported cases of hypertension associated with the deoxycholate formulation of AmB.

Topics: Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Child; Drug Combinations; Female; Humans; Hypertension; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols

New approaches in successful treatment of cancer patients are impaired by increasing incidence of fungal infections with high mortality. Relevant prognostic factors could be identified by numerous trials, such as age, kind and status of disease, intensity of previous chemotherapy, bone marrow transplantation, advanced fungal colonization of gastrointestinal tract. In clinical practice options for prompt and sensitive diagnostics are limited despite of new PCR-techniques. Prophylactic efficiency of polyenes or azoles is proven in high risk patients. Amphotericin B is established for treatment in case of documented or assumed invasive fungal infection. Liposomal preparations are less toxic and at least as effective as conventional amphotericin B in randomized trials.

Topics: Amphotericin B; Antibodies, Fungal; Antifungal Agents; Azoles; Candidiasis; Humans; Neoplasms; Risk Factors

The extensive use of antifungal prophylaxis may have played a role in the increased incidence of invasive fungal infections in immunocompromised patients. Amphotericin B remains the antifungal agent with the broadest spectrum of action available and is thus the standard treatment for immunocompromised patients with proven or suspected fungal infections, especially aspergillosis. However, its potential for nephrotoxicity limits its usefulness. Lipid formulations of amphotericin B may allow therapy to be administered with reduced renal toxicity. Three different lipid formulations of amphotericin B are currently available. These compounds have different pharmacokinetics properties and usually achieve higher serum and/or tissue concentrations than amphotericin B. At present, there are no studies comparing the lipid formulations with each other and only a few randomized trials comparing them with conventional amphotericin B. However, a number of open clinical trials and compassionate-use protocols suggest that lipid-based forms of amphotericin B can achieve good response rates with minimal toxicity in patients with a variety of invasive mycoses, including those who have proved refractory or intolerant to previous therapy with conventional amphotericin B. Unfortunately, the cost of these compounds remains very high and may represent a limiting factor to their use.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Candida; Candidiasis; Drug Resistance, Microbial; Humans; Immunocompromised Host; Lipids; Liposomes; Mycoses; Neoplasms; Risk Factors

The high frequency of oropharyngeal candidiasis in immunocompromised patients has led many institutions to develop protocols to guide the use of antifungal agents in the treatment of this opportunistic infection. However, few specific recommendations have been made for directing the management of oropharyngeal candidiasis in patients infected with HIV. To meet this need, a panel of experts representing a variety of disciplines met to formulate a consensus and devise a treatment strategy for clinical application. Among other recommendations, the algorithm calls for use of a topical agent for the treatment of initial and recurring oropharyngeal candidiasis in HIV-infected patients, provided there is no esophageal involvement, patients' CD4+ lymphocyte cell count is >50 cells/mm3, and they are currently receiving or expected to receive effective antiretroviral treatment. For episodes of oropharyngeal candidiasis with concurrent esophageal involvement or where patients have a CD4+ cell count of <50 cells/mm3, are not receiving or anticipating highly active antiretroviral therapy (HAART), and have a high viral load, the algorithm suggests a systemic oral azole as the more appropriate treatment choice. Acute treatment of all oropharyngeal candidiasis episodes is preferred. Chronic suppressive antifungal treatment is to be avoided in recognition of the potential for the development of drug-resistant infection.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; AIDS-Related Opportunistic Infections; Algorithms; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Candidiasis; Candidiasis, Oral; Clotrimazole; Dosage Forms; Esophagitis; Humans; Imidazoles; Viral Load

Topics: Amphotericin B; Antifungal Agents; Azoles; Candidiasis; Child; Flucytosine; Griseofulvin; Humans; India; Mycoses

This article highlights some aspects of candidosis which were explored in different models and which yielded relevant information with respect to pathogenesis as well as possibilities of prevention and treatment of candidosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Fungal Vaccines; Humans

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Chemistry, Pharmaceutical; Fluconazole; Flucytosine; Hematologic Diseases; Humans; Itraconazole; Mycoses

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Azoles; Candidiasis; Catheters, Indwelling; Diagnosis, Differential; Flucytosine; Fusarium; Humans; Iatrogenic Disease; Immunocompromised Host; Mycoses; Opportunistic Infections; Syndrome; Trichosporon

Incorporation of amphotericin B into small unilamellar liposomes (AmBisome) alters the pharmacokinetic properties of the drug, but allows it to retain significant in vitro and in vivo activity against fungal species, including Candida, Aspergillus and Cryptococcus, and parasites of the genus Leishmania. Used as prophylaxis against fungal infections in immunocompromised patients, liposomal amphotericin B appeared to reduce the incidence of both fungal colonisation and proven fungal infections, but did not affect overall survival. Empirical therapy with liposomal amphotericin B in immunocompromised adults or children with suspected fungal infections was at least as effective as therapy with conventional amphotericin B. In the largest noncomparative studies, liposomal amphotericin B produced mycological eradication in 40 and 83% of patients with proven Candida infections and 41 and 60% with proven Aspergillus infections; however, these studies included relatively few patients. Mycological eradication rates of 67 to 85% in patients with cryptococcal meningitis have been reported. Liposomal amphotericin B is an effective treatment for visceral leishmaniasis in immunocompetent adults and children, including those with severe or drug-resistant disease. The drug also produces good response rates in immunocompromised patients; however, relapse rates in these patients are high. Liposomal amphotericin B is generally well tolerated. Few patients require discontinuation or dose reduction of the drug because of adverse events. The most frequently reported adverse events are hypokalaemia, nephrotoxicity and infusion-related reactions; however, these occur significantly less often after liposomal amphotericin B than after the conventional formulation of the drug. The acquisition cost of liposomal amphotericin B is higher than that of conventional amphotericin B. Cost-effectiveness analysis did not clearly show an economic benefit for empirical liposomal amphotericin B antifungal therapy in adults; however, one model suggested that initial empirical therapy with the liposomal formulation in children may cost less per cure than initial therapy with the conventional formulation. Liposomal amphotericin B appears to be an effective alternative to conventional amphotericin B in the management of immunocompromised patients with proven or suspected fungal infections. Use of the drug is facilitated by its greatly improved tolerability profile compared with conventional amphoteric

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Drug Carriers; Economics, Pharmaceutical; Humans; Immunocompromised Host; Leishmaniasis, Visceral; Liposomes; Neutrophils

Candida infections in infancy can manifest themselves as skin, mucosal or systemic candidiasis. Eighty to nintey percent of all candida infections in this age group are caused by Candida albicans. Whereas in neonates, infections mostly occur sub partu, in older children predisposing underlying diseases get an increasing etiological importance. The diagnosis is based on microscopic and cultural detection of yeast as well as on the course of the titers of Candida antigen and antibodies. For topical antifungal treatment of skin and mucosa infections, different preparations of the polyenes nystatin and amphotericin B have been proven to be most effective. In systemic candidiasis the combination of amphotericin B and 5-flucytosin is the treatment of choice. In view of the potential severe side effects of this combination therapy, fluconazol as a sole treatment represents an effective alternative. Prophylaxis against Candida infections comprises sticking to hygienic regimes, mycological surveillance of risk groups and oral application of antimycotics.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Child, Preschool; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; Humans; Infant; Infant, Newborn; Male; Risk Factors

Fungal infections of total joint arthroplasties are extremely rare with only 21 previous reported cases in the literature. In 19 of these cases, the offending organism has been a member of the candida species. In all of these cases, the patients had no clinical evidence of disseminated fungal infection. All previously reported cases of total joint fungal infections required removal of the primary prosthesis to eradicate the infection. There has also been a great reluctance to reimplant these patients. In fact, reimplantation has been successful in only one reported case. We report the first case of successful salvage of an arthroplasty infected with candida.

Topics: Abscess; Amphotericin B; Antifungal Agents; Arthritis, Infectious; Candidiasis; Combined Modality Therapy; Hip Prosthesis; Humans; Male; Middle Aged; Osteoarthritis, Knee; Reoperation; Surgical Wound Infection; Synovectomy; Synovitis

Topics: Amphotericin B; Animals; Antifungal Agents; Azoles; Candidiasis; Drug Interactions; Flucytosine; Humans

Torulopsis glabrata is a yeastlike fungus that has recently become recognized as an important opportunistic pathogen. Only four cases of T glabrata infection in neonates have been reported. We report two cases of fungemia caused by this organism in premature infants. Both patients were treated with amphotericin B and survived the fungemia, but one patient later died of bacterial sepsis. Both patients had been treated with surfactant, artificial ventilation, intravascular catheters (arterial and venous), broad spectrum antibiotics, and hyperalimentation, which appear to be risk factors for T glabrata fungemia. A review of the literature indicates that T glabrata is susceptible to amphotericin B and 5-fluorocytosine and is resistant to fluconazole. In addition, it is less susceptible to ketoconazole, clotrimazole, and itraconazole than is Candida albicans. We recommend that T glabrata infections be treated initially by reducing iatrogenic risk factors and beginning amphotericin B therapy. If necessary, 5-fluorocytosine should be added to the drug regimen.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Fatal Outcome; Female; Humans; Infant, Newborn; Infant, Premature; Respiration, Artificial

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Celiac Artery; Cytomegalovirus Infections; Female; Heart Transplantation; Humans; Immunocompromised Host; Immunosuppression Therapy; Incidence; Liver Transplantation; Male; Middle Aged; Mucormycosis; Mycoses; Postoperative Complications; Risk Factors; Thrombosis; Time Factors; Transplantation; Triazoles

Five cases of candidal meningitis in human immunodeficiency virus (HIV)-infected patients have been diagnosed in our hospital. This article describes these cases and reviews another nine previously reported in the literature. Most patients (71%) had at least one well-known predisposing factor for candidiasis. Median CD4 cell count was 135/mm3. Headache and fever, in the absence of focal neurologic signs, were the predominant clinical features. The CSF analysis revealed mild pleocytosis and hypoglycorrachia, indistinguishable from those seen in tuberculous or cryptococcal meningitis. Twelve patients (92%) received amphotericin B for a median of 51 days, in combination with flucytosine in five cases. The overall mortality among treated patients was 31%. Although the risk of relapse of candidal meningitis is unknown, maintenance antifungal therapy was given to seven patients (63%), usually with fluconazole. Candida species must be kept in mind as a cause of chronic meningitis in HIV-infected patients who have a known predisposing factor.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candidiasis; Female; Fluconazole; Flucytosine; Humans; Male; Meningitis, Fungal; Middle Aged; Risk Factors

We describe congenital cutaneous candidiasis (CCC) in a term newborn. The mother had candidal vaginitis 1 week before delivery. At birth, the infant had a generalized, intensely erythematous, papulovesicular eruption, respiratory distress and elevation of liver function tests. The child responded well to intravenous amphotericin B plus topical and oral nystatin. There have been 13 previously reported cases of CCC in infants weighing more than 1500 gm who had evidence of systemic infection. Two deaths were attributed to candidal pneumonia and sepsis. The majority of infants with CCC have infection localized to the skin, but if there is any evidence of respiratory distress or signs of sepsis the possibility of systemic candidiasis and the need for parenteral antifungal therapy must be considered.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Candidiasis, Cutaneous; Candidiasis, Vulvovaginal; Drug Therapy, Combination; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Liver Function Tests; Nystatin; Pregnancy; Pregnancy Complications, Infectious; Respiratory Distress Syndrome, Newborn

The availability of standard guidelines (NCCLS M27 document) for antifungal susceptibility testing has facilitated the establishment of tentative interpretive breakpoints for fluconazole and itraconazole by the NCCLS. Based on correlations of MIC values with the outcomes of patients with mostly Candida infections, fluconazole MICs of > or = 64 and itraconazole MICs of > or = 1.0 microgram/mL are considered resistant. Fluconazole MICs of 16 to 32 micrograms/mL and itraconazole MICs of 0.2 to 0.5 microgram/mL were categorized as "susceptible dependent upon dose" (S-DD), that is, clinical response may be obtained with increased doses. Susceptible breakpoints for fluconazole and itraconazole correspond to < or = 8 and < or = 0.12 microgram/mL, respectively. For flucytosine, resistant and susceptible breakpoints for Candida were set at > or = 32 micrograms/mL and 4 micrograms/mL, respectively, based on historical data and the drug's pharmacokinetics for Candida. Although no breakpoints have been established for amphotericin B, clinical failure has been associated with MICs > 1.0 microgram/mL.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Cryptococcosis; Drug Resistance, Microbial; Fluconazole; Flucytosine; Humans; Itraconazole; Mycoses

Topics: Amphotericin B; Aspergillosis; Candidiasis; Child; Coccidioidomycosis; Cytokines; Diagnosis, Differential; Fluconazole; Histoplasmosis; Humans; Itraconazole; Mucormycosis; Mycoses; Prognosis

Hematogenous candidiasis is associated with substantial mortality and morbidity. Amphotericin B has routinely been used to treat this infection. However, tolerance of therapy with amphotericin B is limited by the drug's toxicity. The results of recently completed prospective randomized clinical studies comparing amphotericin B with fluconazole for the treatment of hematogenous candididiasis suggest that fluconazole is as effective as amphotericin B and that fluconazole is better tolerated by patients. Nevertheless, several questions remain to be answered regarding the optimal choice of antifungal agent for both nonneutropenic and neutropenic patients, the dosing schedule and duration of therapy, the role of combination antifungal therapy, and the efficacy of the lipid formulations of polyenes. Controversial issues with respect to the role of central venous catheters in the pathogenesis of hematogenous candidiasis, as well as the roles of cytokines and white blood cell transfusions in the treatment of neutropenic patients with hematogenous candidiasis, also need to be addressed.

Topics: Algorithms; Amphotericin B; Antifungal Agents; Candidiasis; Catheterization, Central Venous; Colony-Stimulating Factors; Drug Administration Schedule; Drug Therapy, Combination; Fluconazole; Fungemia; Humans; Leukocyte Transfusion; Liposomes; Neutropenia; Randomized Controlled Trials as Topic

In summary, the recent increase in frequency of systemic fungal infections has stimulated the development of new antifungal agents which are easier to use and which have decreased toxicity. This has resulted in increase in use, and along with this, the appearance of fungi resistant to antifungal agents. The medical community will have to come to terms with this newly emerging problem.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Drug Resistance, Microbial; Fluconazole; Humans; Mycoses; Sterols

On the basis of intestinal yeast colonization different consequences for therapeutic and prophylactic administration of polyene antimycotics have to be drawn. Immunocompromised neutropenic patients should orally receive polyene antifungal drugs (nystatin or amphotericin B) for a long time during the period of increased risk for systemic candidosis. The level of daily dosing is dependent on age, physiological status of the gastrointestinal tract, and underlying disease of the patient. In immunocompetent persons the normal commensal yeast flora should not be suppressed by antifungal chemoprophylaxis if no clinical indications are present, because permanent eradication of yeast in the intestinal tract ist not attainable. About 5 to 15 days after finishing the administration of polyene antimycotics the fungi are detectable again in the faeces in low quantities. The influence of orally administered polyene drugs in the intestinal tract may be detected shortly after starting the application. Thus efficient concentrations of nystatin and amphotericin B are continuously present in the faeces 24 to 48 hours after beginning until 2 to 10 days after finishing the administration. During this time the quantity of yeast in the faeces is evidently reduced or not longer detectable by fungal culture. The oral administration of polyene antimycotics for a long time in persons without immunodepression and without heavy intestinal yeast colonization is not justified.

Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Candidiasis; Colon; Feces; Humans; Immunocompromised Host; Nystatin; Polyenes; Risk Factors; Yeasts

Renal papillary necrosis (RPN) due to Candida is a rare disease with only 19 cases reported over the past 37 years. But the diagnosis in 17 of the 19 cases was not made until a necropsy was carried out. The 2 cases that were diagnosed antemortem had radiographic sonography. A singapore case with candidal RPN was described in detail. Candidal RPN was associated with underlying diseases in all these cases. The disease may be more frequently encountered in the future with the advent of radiographic tools like sonography which was not described prior to 1980. Indeed, patients with underlying diseases who develop persistent candiduria should have radiographic investigation of the urinary tract to detect candidal RPN to that early remedial measures can be carried out.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Diabetes Mellitus, Type 2; Female; Humans; Kidney; Kidney Diseases; Necrosis; Radiography

This article describes a case of total knee infection by Candida parapsilosis treated by joint reimplantation. Surgical treatment consisted of resection arthroplasty with wound stablization by external fixation. Antibiotic treatment consisted of 6 weeks of intravenous amphotericin B and 7 weeks of oral 5-fluorocytosine begun at the time of resection arthroplasty. Cultures at reimplantation were negative. Reimplanted components were all cemented with perioperative cefazolin antibiotic. No further antifungal treatment was necessary.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Combined Modality Therapy; External Fixators; Female; Flucytosine; Humans; Knee Prosthesis; Middle Aged; Prosthesis Design; Prosthesis-Related Infections; Reoperation

As is the case with antibacterial agents, the increasing use of antifungal agents has led to development of antifungal resistance, the most clinically important of which is the resistance of Candida to fluconazole. While mutation to high-level fluconazole resistance is possible, the most important aspect of fluconazole resistance for patients in the ICU is the possibility of an epidemiologic shift away from such susceptible species as C. albicans and C. parapsilosis toward the most resistant species, such as C. glabrata and C. krusei. Resistance to amphotericin B by Candida is also possible, but less frequent. Strategies for treating invasive Candida infections must consider the relative rates of non-C. albicans Candida infection and the likelihood of antifungal resistance. The agents that cause invasive mold infections in the ICU are intrinsically moderately resistant to the available antifungal agents, and therapy depends less on the choice of antifungal therapy than on the correction of predisposing factors. The role of susceptibility testing as a guide in selecting appropriate therapy for all of these infections is as yet incompletely defined, but testing for resistance to fluconazole may soon be ready for clinical use.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Drug Resistance, Microbial; Fluconazole; Humans; Intensive Care Units

Amphotericin B (AmB), the drug of choice for the treatment of most systemic fungal infections, is marketed under the trademark Fungizone, as an AmB-deoxycholate complex suitable for intravenous administration. The association between AmB and deoxycholate is relatively weak; therefore, dissociation occurs in the blood. The drug itself interacts with both mammalian and fungal cell membranes to damage cells, but the greater susceptibility of fungal cells to its effects forms the basis for its clinical usefulness. The ability of the drug to form stable complexes with lipids has allowed the development of new formulations of AmB based on this property. Several lipid-based formulations of the drug which are more selective in damaging fungal or parasitic cells than mammalian cells and some of which also have a better therapeutic index than Fungizone have been developed. In vitro investigations have led to the conclusion that the increase in selectivity observed is due to the selective transfer of AmB from lipid complexes to fungal cells or to the higher thermodynamic stability of lipid formulations. Association with lipids modulates AmB binding to lipoproteins in vivo, thus influencing tissue distribution and toxicity. For example, lipid complexes of AmB can be internalized by macrophages, and the macrophages then serve as a reservoir for the drug. Furthermore, stable AmB-lipid complexes are much less toxic to the host than Fungizone and can therefore be administered in higher doses. Experimentally, the efficacy of AmB-lipid formulations compared with Fungizone depends on the animal model used. Improved therapeutic indices for AmB-lipid formations have been demonstrated in clinical trials, but the definitive trials leading to the selection of an optimal formulation and therapeutic regimen have not been done.

Topics: Amphotericin B; Animals; Aspergillosis; Blastomycosis; Candidiasis; Cell Death; Cell Membrane; Clinical Trials as Topic; Coccidioidomycosis; Cryptococcosis; Detergents; Drug Carriers; Drug Delivery Systems; Drug Industry; Histoplasmosis; Immunity, Active; Leishmania; Leishmaniasis, Visceral; Lipoproteins; Mice; Molecular Structure; Phospholipids; Rabbits

We conducted a prospective, randomized, multicenter study comparing fluconazole and amphotericin B in the treatment of candidal infections. One hundred and sixty-four patients (60 of whom were neutropenic) with documented or presumed invasive candidiasis were assigned to treatment with either fluconazole (400 mg daily) or amphotericin B (25-50 mg daily; 0.67 mg/kg daily for neutropenic patients). Clinical response and survival rates were assessed at 48 hours, after 5 days, and at the end of therapy. Overall response rates to fluconazole and amphotericin B were similar (66% and 64%, respectively). There were no differences in response as related to site of infection, pathogen, time to defervescence, relapse, or survival rates between the groups. Adverse effects were more frequent with amphotericin B (35%) than with fluconazole (5%; P < .0001). The results of this study confirm that fluconazole is as effective as but better tolerated than amphotericin B in the treatment of candidal infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Candidiasis; Female; Fluconazole; Humans; Male; Prospective Studies; Treatment Failure; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Arthritis, Infectious; Candidiasis; Child; Drug Administration Schedule; Fluconazole; Follow-Up Studies; Humans; Injections, Intravenous; Knee Injuries; Male

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Flucytosine; Humans; Mycoses; Myocarditis; Prognosis

Fungal arthritis (FA) due to a candida infection was reviewed in English literature and described in 45 cases. The increasing use of potent antibiotics, immunosuppressives, and especially the use of artificial joints, predisposed to the infection. Weightbearing joints, particularly the knees, were most frequently affected. Symptoms were described as a warm, tender and swollen joint, and the duration of symptoms prediagnosis was described as being up to 4 years. Amphotericin B was the treatment drug of choice, and in cases of no response, supplemented with either flucytosine or ketoconazole. Local FA healed in all cases. FA in an artificial joint resulted in all cases in removal of the prostheses. Mortality in systemic fungal infections including FA was 50%.

Topics: Amphotericin B; Antifungal Agents; Arthritis, Infectious; Candidiasis; Humans; Synovial Fluid

Purulent pericarditis caused by Candida species is a rare and often undiagnosed disease. We recently treated a patient in whom purulent pericarditis due to Candida albicans developed following thoracic surgery. The patient survived after receiving a combination of surgical and medical therapy. A literature review revealed 24 additional cases of purulent pericarditis caused by Candida species. Twenty-one of the patients either had undergone thoracic surgery or had had disseminated candidiasis. None of the 12 patients described before 1980 survived, whereas six (46%) of the 13 patients described after 1980 survived. No patient survived without pericardiectomy (five of six survivors) or at least pericardiocentesis (one survivor). All survivors received full courses of amphotericin B therapy. An increased utilization of echocardiography, along with an increased recognition of the patient populations at risk, has been instrumental in early detection and improved outcome of purulent pericarditis. A combination of prolonged amphotericin B therapy and pericardiectomy appears to be the best approach for achieving a cure.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Echocardiography; Humans; Male; Pericardial Effusion; Pericardiectomy; Pericarditis; Thoracic Surgery

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Clinical Trials as Topic; Disease Susceptibility; Drug Administration Routes; Hematopoietic Cell Growth Factors; Humans; Immunocompromised Host; Leukocyte Transfusion; Mycoses; Neoplasms; Neutropenia; Triazoles

The significance of candiduria ranges from simple procurement-related contamination to disseminated candidiasis. Ensuring that a valid urine specimen is collected and carefully assessing patients for risk factors predisposing to disseminated candidiasis permit the stratification of cases into three clinical categories: (1) asymptomatic candiduria in a previously healthy patient; (2) candiduria in a high-risk patient in whom disseminated candidiasis is unlikely; and (3) candiduria in a high-risk patient with a potential for disseminated candidiasis. Strategies for management are tailored to the individual patient. Appropriate management of anatomic genitourinary abnormalities and removal of bladder catheters may result in the resolution of candiduria, although some patients require systemic antifungal therapy. All patients with candiduria should be evaluated for evidence of deep-seated tissue infection or candidemia before therapy is instituted. Fluconazole appears to be a safe and effective agent for the management of candidal urinary tract infection. Both its safety and its ease of administration make it superior to amphotericin B for this purpose.

Topics: Algorithms; Amphotericin B; Animals; Azoles; Candidiasis; Flucytosine; Humans

Candidemia results in a mortality of > 50% among adults, but data on children with candidemia are limited. We reviewed 70 episodes of pediatric candidemia that occurred between January 1988 and October 1992. Of these episodes, 53% were caused by Candida albicans, 24% were caused by Candida parapsilosis, 16% were caused by Candida tropicalis, and 3% were caused by Candida krusei. Twenty-five percent of the patients were premature infants. Other underlying conditions included malignancy (15%); cardiac disease (14%); and short-gut syndrome (14%). A central venous catheter was in place during 61 (87%) of 70 episodes. Candiduria preceded candidemia in only 4 (8%) of 52 patients. The overall mortality rate was 19%; 36% of those with intravenous catheters that were not removed within 3 days died, whereas none of the patients from whom catheters were removed within 3 days died (P < .0001). Only two survivors had complications. Therapy with amphotericin B (with or without flucytosine) was administered to 74% of these patients. Seventeen patients were not treated medically; all were immunocompetent and survived. Of these patients, 15 were > 2 months of age; 14 had candidemia for < or = 2 days; and 15 had an intravenous catheter removed within 2 days of the onset of candidemia. No patient stopped receiving amphotericin B because of side effects. The results of this study suggest the following: that mortality associated with candidemia is lower among children than among adults; that failure to remove the indwelling intravenous catheter usually results in a poor outcome; that candiduria rarely precedes candidemia in children; and that amphotericin B is well tolerated by children.

Topics: Adolescent; Age Distribution; Amphotericin B; Candidiasis; Child; Child, Preschool; Drug Therapy, Combination; Female; Flucytosine; Fungemia; Humans; Infant; Infant, Newborn; Male; Treatment Outcome

Candidal endophthalmitis is a sight-threatening ocular infection that most frequently occurs as a complication of candidemia. While amphotericin B is considered the gold standard for the treatment of most invasive fungal infections, the optimal management of candidal endophthalmitis has not been determined. Fluconazole, a triazole antifungal agent, has been shown to be effective in the management of a number of invasive fungal infections in both immunocompromised and immunocompetent hosts. We describe the clinical features and outcomes for six patients with candidal endophthalmitis who were treated with fluconazole at our institutions, and we review 21 additional cases reported in the English-language literature. In total, fluconazole has been used as the sole therapy for candidal endophthalmitis in 14 patients; 16 eyes were infected. Endophthalmitis was cured in 15 of 16 eyes (94%), including five infections that were complicated by vitreitis. Successful treatment required the administration of fluconazole (100-200 mg po) daily for approximately 2 months. In addition, fluconazole has been used in combination with pars plana vitrectomy for the successful treatment of four cases of candidal endophthalmitis that were complicated by moderate to severe vitreitis. Fluconazole appears to be a safe and effective alternative or addition to conventional treatments for the management of candidal endophthalmitis. Prospective evaluation is required to more clearly define the role of this antifungal agent in the management of ocular infections due to Candida species.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Candidiasis; Drug Administration Schedule; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Fungal; Female; Fluconazole; Follow-Up Studies; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome

Candidal infection has been associated extensively with serious infections. Its role in genital tract infections has consisted largely of vulvovaginitis, with serious upper genital tract infection a rarity. A 47-year-old woman with an intrauterine device had Candida glabrata in a large tuboovarian abscess and recovered only after removal of the abscess and treatment with amphotericin B.

Topics: Abscess; Amphotericin B; Candidiasis; Combined Modality Therapy; Fallopian Tube Diseases; Female; Humans; Intrauterine Devices, Copper; Middle Aged; Ovarian Diseases

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases

Three cases of candida meningitis were encountered in a 3-year period in our hospital; all occurred in neurosurgical patients. We describe these three cases and review the 15 cases of neurosurgery-related candida meningitis previously reported in the English-language literature. Data regarding these 18 patients formed the basis for our review. Most patients with candida meningitis had recently received antibacterial agents, and it is notable that 50% of patients suffered from antecedent bacterial meningitis. The CSF analysis revealed neutrophilic pleocytosis that was indistinguishable from that of bacterial meningitis. The overall mortality was 11%. Administration of amphotericin B combined with flucytosine appeared to be the best therapeutic approach for candida meningitis.

Topics: Adult; Aged; Amphotericin B; Anti-Infective Agents; Antifungal Agents; Brain; Candidiasis; Drug Therapy, Combination; Female; Flucytosine; Humans; Male; Meningitis, Bacterial; Meningitis, Fungal; Middle Aged; Postoperative Complications

Right atrial thrombus formation is a rare complication of central venous catheterization in adults. Infection of this thrombus is exceptional. A case of a right atrial thrombus associated with Candida albicans infection is described. Surgical thrombectomy, withdrawal of the catheter, and long-term antiinfectious therapy seem the only appropriate treatment. The literature on this unusual condition is reviewed.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Catheterization, Central Venous; Coronary Thrombosis; Female; Heart Atria; Humans; Middle Aged; Sepsis; Thrombectomy; Ultrasonography

In clinical medicine mere colonization with yeasts is often hardly to be discriminated from true infection. Thus, a clear-cut separation of preventive from therapeutic use of antimycotics is not possible in practical medicine. The problem is that on the one hand one has no exact diagnosis of yeast infection, but on the other hand best therapeutic results are obtained when the drugs are given as early as possible. In comparison to the huge number of antibacterial compounds, the members of antimicrobials are limited. For prophylaxis, one can use the polyenes, such as amphotericin B and nystatin, or the azoles, such as fluconazole or itraconazole. Thereby the azoles act not only locally at the site of application but are absorbed and thus are distributed to remote sites, where the non-resorbable polyenes never arrive. Among the azoles, fluconazole has the advantage that resorption is independent from an acid pH in the stomach, whereas itraconazole resorption is variable in severely ill persons with neutralized gastric fluid. For therapeutic use systemically applied amphotericin B has certain disadvantages. Because of toxic reactions an optimal dose cannot be given; furthermore in some sites insufficient concentrations are achieved, particularly in the kidney and also in the CSF. In contrast, the azoles possess better pharmacologic and toxicologic properties. Resistance to antimycotics is principally possible but still rare, so that in practice a routine testing is not necessary. Candida glabrata as well as Candida krusei are primarily resistant to fluconazole.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candidiasis; Chemistry, Pharmaceutical; Drug Resistance, Microbial; Ergosterol; Fluconazole; Humans; Mycoses; Yeasts

Invasive fungal infection remains a major problem in transplant recipients. The commonest causes of infection are Candida, and Aspergillus spp., although a growing number of other organisms (including species of Fusarium and Trichosporon) have been reported to cause infection in neutropenic bone marrow transplant recipients. The clinical manifestations of these infections are described and methods of diagnosis are discussed. As in other groups of immunocompromised patients, the diagnosis is often difficult to establish, but transplant recipients who are given empirical treatment with amphotericin B have increased rates of survival. The roles of lipid-associated forms of amphotericin B and of the triazole compounds, itraconazole and fluconazole, in the treatment and prevention of fungal infection are discussed.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Azoles; Candidiasis; Humans; Mucormycosis; Mycoses; Postoperative Period; Risk; Transplantation

Horton giant cell arteritis can present with an atypical clinical picture that often resembles other diseases. In the case described below, the patient initially demonstrated clinical and laboratory evidence of a Candida albicans sepsis, and therefore we started antimycotic treatment with amphotericin B. Because of an adverse reaction to that drug, we added parenteral steroids before every administration of the antimycotic which led to an unexpected improvement of symptoms. This result caused us to reconsider some clinical aspects that could have been interpreted also as vasculitis, in particular for a giant cell arteritis: throbbing temporal headache, diffuse weakness, important rise in ESR, myoarthralgias. We performed a biopsy of the temporal artery that confirmed our diagnosis.

Topics: Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Biopsy; Candidiasis; Drug Hypersensitivity; Drug Therapy, Combination; Giant Cell Arteritis; Humans; Hydrocortisone; Male; Middle Aged; Prednisone; Recurrence; Temporal Arteries

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Candidiasis, Chronic Mucocutaneous; Clinical Trials as Topic; Cryptococcosis; Double-Blind Method; Fluconazole; Humans; Itraconazole; Ketoconazole; Mucormycosis; Mycoses; Neutropenia; Nystatin; Primary Prevention; Recurrence; Retrospective Studies

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Candidiasis, Oral; Candidiasis, Vulvovaginal; Child; Clinical Trials as Topic; Cryptococcosis; Drug Resistance, Microbial; Esophageal Diseases; Female; Fluconazole; Fungi; Humans; Ketoconazole; Male; Retrospective Studies

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Clinical Trials as Topic; Coccidioidomycosis; Cryptococcosis; Fluconazole; Flucytosine; Hematologic Diseases; Histoplasmosis; Humans; Itraconazole; Ketoconazole; Kidney; Mycoses; Thrombophlebitis

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Candidiasis, Oral; Clinical Trials as Topic; Dermatomycoses; Esophageal Diseases; Humans; Itraconazole; Meningitis, Cryptococcal; Mycoses; Pharyngeal Diseases; Tropical Medicine

Obstructive uropathy caused by upper urinary tract fungal ball formation is an uncommon but well recognized clinical entity. The clinical course and management of an infant with unilateral fungal ball obstruction is described. Ultrasound and Tc-diaminotetraethylpentacetic acid (DTPA) renal scan contributed significantly to the diagnosis and management of this patient. Complete resolution of the obstruction was achieved by treatment with intravenous amphotericin B and oral 5-fluorocytosine. The clinical course and management of 35 patients described in the literature indicate that prematurity, use of broad spectrum antibiotics, prolonged hospital stay and the use of intravascular catheters are predisposing factors. The mortality rate is 34%. Young age, small size, the presence of candidaemia and withholding antifungal therapy are poor prognostic factors. A rational plan of treatment, extrapolated from the literature, is presented which may help to reduce the mortality rate in this condition.

Topics: Amphotericin B; Candidiasis; Drug Therapy, Combination; Flucytosine; Humans; Hydronephrosis; Infant; Infant, Newborn; Kidney Diseases; Kidney Pelvis; Male; Ureteral Obstruction

During the last years, the proportion of cancer patients who develop systemic fungal infections has increased steadily. These infections are characterised by high mortality, especially in patients with persistent granulocytopenia and in those receiving allogeneic bone marrow transplants. The most important pathogens in neutropenic patients are Candida and Aspergillus spp. Usually, Candida infections arise from overgrowth in the gastrointestinal tract, while Aspergillus infections are acquired by inhalation of spores. Prophylaxis of systemic fungal infections seems mandatory since optimal strategies for diagnosis and treatment of these infections are lacking. Treatment with the non-absorbable polyenes nystatin and amphotericin B is useful for prophylaxis of superficial fungal infections, provided that compliance of the patients is optimal. The imidazoles ketoconazole and miconazole can reduce the incidence of superficial fungal infections, but there are conflicting data regarding their value for prevention of systemic mycoses. There are several studies indicating that prophylactic use of fluconazole reduces the incidence of mucosal and systemic fungal infections, especially in patients receiving allogeneic bone marrow transplants. Fluconazole shows reduced activity against several Non-albicans spp. and is not active against Aspergillus spp. Itraconazole has in vitro and in vivo activity against several Aspergillus spp. but high serum and tissue levels are necessary. However, bioavailability of itraconazole is reduced in patients with raised gastric pH and no i.v. formulation is available. Although there is some evidence for its prophylactic activity against Aspergillus infections in neutropenic patients, more studies are necessary to confirm these findings. Intravenous amphotericin B cannot be recommended for routine prophylactic use because of its toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Fluconazole; Granulocyte Colony-Stimulating Factor; Humans; Incidence; Itraconazole; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections

Deep seated candidosis are the most common invasive fungal infections occurring in various categories of patients including those with cancer, burns as well as patients with AIDS or undergoing organ transplantation. Various clinical entities have to be distinguished with implications for diagnostic procedures as well as for adequate therapy. During the last decade, tremendous progress has been achieved leading to a major reduction of mortality attributable for candidaemia from 80% (in the seventies) to 40% in the nineties, mainly due to early empiric antifungal and better prophylaxis treatment. Other antifungal strategies than conventional amphotericin B are now available and have been shown effective, in particular, new modalities to administer amphotericin B including various lipid formulations, but also new azoles and mainly the triazoles such as fluconazole and itraconazole. Fluconazole has been shown effective as prophylaxis of candidosis including in patients undergoing bone marrow transplantation as well as in treatment of oropharyngeal candidosis and for candidaemia occurring in non-neutropenic patients. More limited data are available on itraconazole so far in particular in patients with documented invasive candidosis, but preliminary reports are encouraging. Oral therapy with systemic efficacy is more easy to recommend and allows ambulatory treatment. Candidosis is not a benign disease and in every single patient with fungemia antifungal treatment is mandatory.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Burns; Candidiasis; Fluconazole; Humans; Incidence; Itraconazole; Neoplasms; Opportunistic Infections; Postoperative Complications; Transplantation

Attachment of antibodies to the surface of liposomes was performed to confer specificity for a certain cell or organ expressing the targeted antigenic determinant. These so-called immunoliposomes are expected to be applied as targeted drug carriers. In this article, the literature concerning in vivo studies of the targeting of immunoliposomes to various sites in the body is reviewed. The anatomical, physiological, and pathological constraints and current progress are described. Moreover, perspectives on the therapeutic feasibility of this drug targeting system are discussed.

Topics: Amphotericin B; Animals; Antibodies, Monoclonal; Antineoplastic Agents; Biological Availability; Candidiasis; Chloroquine; Clinical Trials as Topic; Drug Carriers; Drug Compounding; Drug Evaluation, Preclinical; Humans; Immunoconjugates; Injections, Intravenous; Liposomes; Lung; Lymph Nodes; Malaria; Mice; Neoplasms; Peritoneal Cavity; Plasmodium berghei; Rats; Tissue Distribution

Pancreatic infection remains a significant clinical problem, with substantial morbidity and mortality. Published case reports of Candida species identified in these infections prompted a review of 17 consecutive patients recently treated for peripancreatic infection by scheduled relaparotomy. Six patients were transferred from other hospitals, all having undergone prior operative intervention (median stay elsewhere: 58 days). The 11 other patients underwent initial operation an average of 14 days after admission. Candida species were identified in the initial operative cultures of 5 patients (29%), three of whom had undergone previous drainage at other hospitals. Two patients (11.7%) had Candida identified at subsequent operation. Six patients were treated with Amphotericin B for a median of 12 days (range 6-32) and a median dosage of 420 mg (range 225-830 mg). All patients were cleared of their Candida infection, but three subsequently died, for an overall mortality of 17.6%. Candida infected patients suffered a 42 per cent mortality. Our series supports the suspicion that Candida is much more frequent (41% of patients) than previously recognized in peripancreatic sepsis, and is commonly acquired after the initial operation. Amphotericin B therapy is effective in clearing Candida infection, but affected patients have a high associated mortality.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Candidiasis; Chronic Disease; Combined Modality Therapy; Drainage; Female; Humans; Incidence; Length of Stay; Male; Middle Aged; Necrosis; Pancreatitis; Reoperation; Severity of Illness Index; Survival Rate; Treatment Outcome

Chronic meningitis is an uncommon manifestation of candidiasis. We present the case of an elderly woman who had symptoms such as headache, malaise, and fever for 8 months and was found to have Candida albicans meningitis, and we review 17 similar cases. An underlying illness or risk factor for candidiasis was present in only 13 (72%) of the 18 patients. Headache, fever, and nuchal rigidity were the predominant clinical findings. Analysis of CSF showed either mononuclear or neutrophilic pleocytosis, an elevated protein level, and a decreased level of glucose. Only 17% of CSF smears were positive, and only 44% of initial CSF cultures yielded Candida species. In four cases, Candida species grew only after special techniques were used; in three cases, CSF cultures remained negative. The overall mortality associated with candidal meningitis was 53%, but among 12 patients who were treated and followed, the rate was 33%. In addition to acute meningitis seen with disseminated infection, Candida species can cause chronic meningitis that mimics tuberculosis and the more common fungal meningitides, such as cryptococcosis.

Topics: Aged; Amphotericin B; Candida albicans; Candidiasis; Cerebrospinal Fluid Proteins; Female; Flucytosine; Glucose; Humans; Leukocyte Count; Meningitis, Fungal; Neutrophils

Unlike the situation with many antimicrobial agents, there is limited experience with the use of amphotericin B during pregnancy. Although reports of fungal infections during pregnancy have been published, few describe fungemia with either Candida or Torulopsis species. We present a case of fungemia due to Torulopsis glabrata that occurred during pregnancy and that was treated with amphotericin B. Drug concentrations were measured in placental tissue, cord serum, and infant serum at delivery. Although the last dose of amphotericin B was administered 4 weeks before delivery, the concentrations in all three specimens were still within the MIC ranges for most strains of Candida albicans and T. glabrata as measured by broth dilution. We speculate that persistent tissue concentrations of amphotericin B most likely contributed to the sustained hypokalemia in the mother and the increased creatinine level in the infant. In the latter case, placental tissue may have served as the reservoir from which amphotericin B was slowly released into fetal circulation.

Topics: Adult; Amphotericin B; Candidiasis; Creatinine; Female; Fungemia; Humans; Hypokalemia; Infant, Newborn; Placenta; Pregnancy; Pregnancy Complications, Infectious

Infections due to Candida spp. are increasingly common. Despite a number of studies examining the characteristics of fungemic (non-neutropenic) patients, there are no prospective studies defining indications for therapy before the appearance of fungemia. This article reviews the potential pathways for dissemination of Candida from the gastrointestinal tract, believed to be the primary entry route for yeast. Particular attention is focused on mucosal shedding at the villous tip and the potential role of microfold cells in this process. Therapeutic usage of amphotericin B, the agent of choice for serious Candida infection, is reviewed, along with usage of 5-flucytosine and fluconazole.

Topics: Amphotericin B; Candidiasis; Clinical Trials as Topic; Cross Infection; Fluconazole; Flucytosine; Fungemia; Gastrointestinal Diseases; Humans; Intensive Care Units; Risk Factors

The Candida species account for approximately three-fourths of fungal infections in patients with cancer. Although Candida albicans is the most frequent cause, C. tropicalis is increasingly implicated as an important pathogen. Over a 12 year period 19 children treated for leukemia at our institution developed C. tropicalis infections. We describe their clinical presentation, extent of fungal infection, treatment, and outcome. Fungemia without meningitis in 11 children was treated successfully, whereas C. tropicalis meningitis in 7 children was uniformly fatal. An additional patient had unsuspected, widespread infection detected at autopsy. Multiple sites, including the cerebrospinal fluid yielded C. tropicalis. Previously reported risk factors including neutropenia, broad-spectrum antibiotic usage, corticosteroid therapy, and total parenteral nutrition were observed in our cases. A high index of suspicion and the early use of aggressive antifungal therapy are critical to the successful management of C. tropicalis infections in children with leukemia.

Topics: Abscess; Adolescent; Amphotericin B; Candida; Candidiasis; Cerebrospinal Fluid; Child; Child, Preschool; Combined Modality Therapy; Drainage; Female; Fluconazole; Fungemia; Humans; Infant; Leukemia; Male; Meningitis, Fungal; Neutropenia; Parenteral Nutrition, Total; Retrospective Studies; Risk Factors; Superinfection; Tennessee

Candidiasis remains the most frequently encountered fungal infection in patients with profound granulocytopenia and appears to be increasing in frequency. In addition, Candida infections are occurring earlier during remission induction chemotherapy and can be caused by a variety of species such as C. albicans, C. tropicalis, and C. krusei. The most frequent source of disseminated infection is the gastrointestinal tract, as the integrity of the epithelium is disrupted by chemotherapeutic agents. The spectrum of disseminated candidiasis comprises both an acute and a chronic presentation (also known in the literature as hepatosplenic candidiasis). The management of disseminated infection consists of early empiric antifungal therapy with a standard agent, amphotericin B. Unfortunately, responses in the setting of profound granulocytopenia appear to be poor. Other agents that appear to be useful in the management of disseminated candidiasis include 5-flucytosine and fluconazole. Based on animal experimentation, it appears that the combination of these three classes of agents might produce superior results compared with amphotericin B alone. Removal of the central venous catheter does not appear warranted in the setting of profound granulocytopenia, and the role of colony stimulating factors needs to be defined. Given the severity and high mortality associated with disseminated candidiasis in patients with hematologic malignancies, antifungal prophylaxis appears warranted.

Topics: Agranulocytosis; Amphotericin B; Candidiasis; Humans; Neoplasms; Randomized Controlled Trials as Topic

Invasive fungal infections are important causes of morbidity and mortality among patients with neoplastic diseases, particularly those with protracted granulocytopenia, those receiving corticosteroids, and those undergoing allogeneic bone marrow transplantation. These mycoses are often difficult to diagnose early, and their treatment is frequently unsuccessful. Antifungal compounds have been used in studies of a variety of preventive strategies including prophylaxis, early empirical therapy, empirical therapy, and secondary prophylaxis. Among all compounds studied thus far, fluconazole has demonstrated the most promising activity in prevention of invasive candidiasis, particularly in adult allogeneic bone marrow transplant recipients. However, fluconazole does not have activity at currently approved dosages against Candida krusei, Torulopsis glabrata, and most filamentous fungi, including Aspergillus species. Empirically administered amphotericin B significantly decreases the frequency of invasive fungal infections in persistently or recurrently febrile granulocytopenic patients. The use of itraconazole for prevention of aspergillosis warrants study. The current lack of reliable preventive regimens against infections due to Aspergillus and against those due to several emerging fungal pathogens presents an ongoing challenge. The use of recombinant human cytokines, transfusion of effector cells, and administration of newer antifungal compounds are new potential modalities for prevention of invasive mycoses.

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cytokines; Drug Administration Routes; Humans; Imidazoles; Neoplasms; Opportunistic Infections; Polyenes; Triazoles

Fenestrated Fontan operation was performed in a 19-year-old male with a diagnosis of right isomerism syndrome. Postoperatively, fungal endocarditis due to Candida Albicans and mediastinitis by Methicilin resistant Staphylococcus Aureus (MRSA) occurred. For Candida endocarditis, combined surgery and medical treatment with amphotericin B was effective. MRSA mediastinitis was successfully treated by continuous closed irrigation with 0.5% povidone-iodine solution. This is the 17th reported case of fungal endocarditis after open heart surgery in Japanese literature.

Topics: Adult; Amphotericin B; Candidiasis; Cardiac Surgical Procedures; Endocarditis; Heart Atria; Humans; Male; Mediastinitis; Methicillin Resistance; Postoperative Complications; Pulmonary Artery; Staphylococcal Infections; Staphylococcus aureus

Candida tropicalis is a well-documented pathogen affecting humans. There is limited clinical and experimental evidence that C. tropicalis causes hematogenous endophthalmitis. We report two cases of C. tropicalis endophthalmitis and review 12 cases reported in the literature. Clinical presentation was similar to that described for Candida albicans endophthalmitis. Therapy with amphotericin B, with or without flucytosine, resulted in resolution of the lesions except in one patient, for whom enucleation of the eye was necessary to control the infection. None of the patients were leukopenic.

Topics: Adult; Amphotericin B; Blood; Candida; Candidiasis; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Fungal; Female; Flucytosine; Humans; Male; Middle Aged

Torulopsis glabrata is a yeast ordinarily considered nonpathogenic. Systemic infection with this yeast occurs in patients who are debilitated, immunosuppressed, diabetic, or receiving multiple antibiotics. We have presented a case of fungemia due to T glabrata in a previously healthy person. The predisposing condition resulting in debility and predisposition to fungemia was major vascular surgery. Treatment with amphotericin B eradicated the fungemia.

Topics: Acute Kidney Injury; Amphotericin B; Aortic Aneurysm; Aortic Dissection; Candida; Candidiasis; Causality; Fungemia; Humans; Male; Middle Aged; Postoperative Complications; Prognosis; Respiratory Distress Syndrome

Candida species are an uncommon cause of infectious arthritis, although the frequency has increased during recent years. Three cases of septic arthritis caused by Candida species are reported, and the literature is reviewed. The first patient developed a popliteal cyst infected by Candida albicans after multiple intravenous antibiotic treatments. The second patient had acute myelogenous leukemia and experienced knee arthritis after chemotherapy, and the third suffered oligoarthritis after a second heart transplantation. All patients received treatment with a standard dose of intravenous amphotericin B. Responses were achieved only in the first two cases; the third patient died despite therapy. Thirty-six previously reported Candida arthritis cases are reviewed, and epidemiologic, diagnostic, therapeutic, and prognostic features are analyzed. Cases are divided into two categories: direct inoculation of fungus and hematogenously disseminated disease; these two categories are compared in terms of sex, age, pathogen species, treatment, and survival. Arthritis induced through direct inoculation of fungus is seen in older individuals, is more frequently produced by species other than C albicans (Candida parapsilosis especially), and has a better prognosis than arthritis caused by disseminated candidiasis. Arthritis can be resolved even in the persistence of the systemic disease. It is believed that the first case of Baker's cyst infected by C albicans and the first case of Candida arthritis in a heart transplant patient are reported here.

Topics: Adolescent; Adult; Amphotericin B; Arthritis, Infectious; Candidiasis; Female; Heart Transplantation; Humans; Immunocompromised Host; Injections, Intra-Articular; Knee Joint; Leukemia, Myeloid, Acute; Male; Middle Aged; Popliteal Cyst; Postoperative Complications; Radiography

Systemic Candida infections are a major cause of infectious morbidity and mortality during chemotherapy-induced neutropenia. Because of the unreliability of conventional diagnostic tests to detect systemic infection early in its course, treatment of established disseminated Candida infection has been generally disappointing with mortality rates of 60-80% in leukemia and bone marrow transplant patients and 30-40% in solid tumor patients. The use of empiric amphotericin B in patients with fever not responding to empiric antibacterial agents has been shown to be successful in reducing morbidity and mortality from fungal infections. However, its toxicity has mitigated the success of this approach. Fluconazole given prophylactically at the institution of chemotherapy has been shown to be a safe and effective alternative. It, however, is not active against all fungal species, especially Aspergillus and some of the less virulent Candida species. Some centers have reported break-through infections by these less susceptible organisms. Whether or not these limitations in its spectrum of activity will limit its usefulness in the future remains unanswered at this time and could pose a cloud to an otherwise bright promise.

Topics: Amphotericin B; Bone Marrow Transplantation; Candidiasis; Disease Susceptibility; Double-Blind Method; Fluconazole; Humans; Immunocompromised Host; Neoplasms; Neutropenia; Survival Rate

Systemic fungal infections are an important cause of morbidity and mortality among immunocompromised patients. New antifungal agents, such as triazoles, are now available, and the place of in vitro tests has to be discussed. It has been shown that interlaboratory reproducibility of in vitro susceptibility tests against fungi was low, due to the lack of standardization. Recently, the NCCLS defined conditions permitting a good interlaboratory reproducibility. However, the predictive value of in vitro susceptibility tests on the therapeutic outcome remain to be demonstrated, and is now under investigation. At the present time, susceptibility testing can be useful: in patients treated by amphotericin B for a severe fungal infection and who do not improve under therapy; to detect resistance to 5-fluorocytosine; to compare the sensitivity to triazoles before and after treatment, in case of therapeutic failure. Serum levels monitoring is useful to prevent the toxicity due to 5-fluorocytosine and to control the digestive absorption of triazoles, especially the lipophilic compound itraconazole.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; In Vitro Techniques; Itraconazole; Ketoconazole; Opportunistic Infections

Candida proliferate within the body of patients with deficient cellular immunity either by the haematogenous route or by adjacency. This condition is often found in hospital patients. It explains the increasing incidence of disseminated candidiasis. They are preferentially found in patients who have had complicated surgery, mostly of the gastrointestinal tract and the heart, or transplant surgery (except for kidney transplants), or who have had prolonged intensive care. Other patients concerned are neonates with a low birth weight, haemato-oncology patients, heroin addicts and AIDS patients. Clinical signs are usually unspecific. When there is widespread involvement, clinical signs can be defined by the secondary locations, especially within the kidneys, lung, endocardium and brain in surgical patients, and liver and spleen in haemato-oncology patients. Eye, skin, gastrointestinal tract, and indeed, muscle lesions which are easily accessible, should be looked for routinely. This helps to ascertain the diagnosis, by showing the presence of Candida in the tissues. Moreover, isolating Candida from places which are normally sterile confirms deep-seated candidiasis. However, the presence of Candida in urine, bronchi, or drainage fluids is only the witness of saprophytism. This underlines the usefulness of immunological tests, which should soon benefit from the availability of new kits for the detection of cytoplasmic antigens. Indeed, the search for antibodies or circulating metabolites do not provide, at present, significantly different results in patients who have only been colonised and in those who have a systemic candidiasis. Interesting results are only obtained by showing the presence of mannans, in research laboratories. For treatment, amphotericin B remains the standard antifungal agent, and the association of amphotericin B with flucytosine the recommended association. However, drugs such as the new triazoles, among which fluconazole is particularly well tolerated and efficient, may considerably alter the principles of treatment. Finally, combining a fungal decontamination of the gut should help reduce the very high death rate of systemic candidiasis.

Topics: Amphotericin B; Candida; Candidiasis; Decontamination; Drug Therapy, Combination; Female; Flucytosine; Humans; Ketoconazole; Male; Miconazole

The increasing incidence of nosocomial candidal infections is a pivotal problem for patients who do not have neutropenia. In contrast with previous principles, candidemia--even in nonneutropenic patients--should be treated with systemic antifungal agents except in rare circumstances. Amphotericin B remains the agent of choice for treatment of hematogenously disseminated candidiasis and for candidemia, although the optimal dosage and duration of this therapy are poorly defined. Therapy with fluconazole is an alternative for patients who are intolerant to amphotericin B; the efficacy of fluconazole compared with that of amphotericin B in hematogenous candidal infections is unknown but is currently being evaluated. Removal of prosthetic devices that are infected with Candida is necessary in nearly all instances to cure the infection. Similarly, removal of an indwelling catheter whose use is associated with candidemia, as opposed to leaving the catheter in place during antifungal therapy, may increase survival rates of patients and lower their rates of complication. Antifungal prophylaxis may be useful for patients who are undergoing transplantation of an organ.

Topics: Amphotericin B; Animals; Candidiasis; Cross Infection; Fluconazole; Fungemia; Humans

Systemic antifungal chemotherapy frequently is more difficult to conduct than antibacterial therapy. Factors that make it difficult include, but are not limited to, common biosynthetic pathways among the eukaryotes and humans, a relative lack of agents, imprecise modes of use, general lack of standardization of in vitro susceptibility tests that have clinical correlations, and, with certain exceptions, lack of clinical correlations with in vitro results of combination antifungal chemotherapy. Amphotericin B has been available for intravenous administration for greater than 30 years and, despite its shortcomings, remains the drug of choice or reference agent in the therapy for many specific systemic fungal infections in various clinical settings. The current role of amphotericin B therapy in these situations and the need for additional controlled, comparative clinical trials with azoles, liposomal amphotericin B, and amphotericin B complex are discussed.

Topics: Amphotericin B; Candidiasis; Cryptococcosis; Drug Resistance, Microbial; Humans; Infusions, Intravenous; Mycoses

Four patients with underlying diseases including multiple trauma, aortic graft infection, and complex fistulae developed acute acalculous cholecystitis with bile cultures positive only for Candida albicans. The primary site of the candida infection included urinary tract, gastrointestinal tract, and an aortic graft in one patient each and was undetermined in the trauma victim. All had received broad-spectrum antibiotics; three of the four were in the intensive care unit (ICU) with organ failure. Ultrasonography showed a thickened gallbladder wall in three patients and sludge in one. Hepato-iminodiacetic acid scans were nonvisualizing in these three patients. Operative findings included gangrenous cholecystitis in two patients and edematous cholecystitis in one. The fourth patient was treated with percutaneous cholecystostomy and interval cholecystectomy. The interval from the onset of symptoms to recognition of the need for operation was an average of 7 days. Two of the four patients died of ongoing sepsis. Candida cholecystitis is a life-threatening complication of critical surgical illness. Risk factors are similar to those for candida infection elsewhere and include antibacterial therapy, complex fistulae, disseminated malignancy, immunosuppression, and prolonged ICU stay. A high index of suspicion for this fungal pathogen and aggressive surgical therapy offer the only chance for a favorable outcome.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Candidiasis; Cholecystectomy; Cholecystitis; Cholecystostomy; Cholelithiasis; Critical Illness; Disease; Female; Humans; Male; Middle Aged; Postoperative Complications; Risk Factors; Surgical Procedures, Operative

118 episodes of fungemia occurring at Rigshospitalet, Copenhagen, between 1984 and 1988 were reviewed retrospectively. Underlying diseases in the patients were dominated by malignancies, primarily hematological disorders, and intraabdominal diseases requiring major abdominal surgery. Predisposing factors identified in the patients were ongoing antibacterial chemotherapy (83%), central venous catheters (72%), major abdominal surgery (39%), and neutropenia (32%). 120 fungal strains were isolated, of which 88 (73%) were Candida albicans, 23 strains representing 8 other Candida species were also isolated, as were 9 strains belonging to 7 other fungal genera. There were only 5 strains resistant to 5-fluorocytosine (MICs greater than or equal to 25 mg/l), and no strain was resistant to amphotericin B. Treatment with antifungal agents was given in 78 patients, generally a combination of amphotericin B and 5-fluorocytosine. In 14 patients (all non-hematological) the only treatment was removal of a permanent central venous catheter. The outcome was poor in patients with hematological disorders (mortality 76%), whereas patients with malignant and non-malignant intraabdominal diseases had a mortality of 35%. All patients with a permanent central venous catheter as the only risk factor recovered rapidly after removal of the catheter.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Child; Child, Preschool; Female; Flucytosine; Hospitals, University; Humans; Infant; Infant, Newborn; Male; Middle Aged; Mycoses; Retrospective Studies; Risk Factors

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Esophagitis; Humans; Nystatin

Topics: Amphotericin B; Candidiasis; Drug Therapy, Combination; Endocarditis; Female; Flucytosine; Humans; Infant, Newborn; Infant, Premature, Diseases; Male

We analysed 7 cases of systemic candida sp. infection diagnosed between 1986 to 1989. Clinical presentation was of sepsis. Evolution was favorable in all, excepting two cases that died due to a candidiasic meningitis and a candidiasic aortic thrombosis, respectively. Almost all patients were treated with amphotericin B only. A newborn had signs of toxicity (thrombocytopenia). We emphasize the importance of a prompt diagnosis and treatment and the effectivity of amphotericin B for systemic candidiasis, besides of its rare toxicity in newborns.

Topics: Amphotericin B; Anti-Bacterial Agents; Candidiasis; Female; Flucytosine; Humans; Infant, Newborn; Male

Invasive fungal infections are common in immunocompromised patients. Early diagnosis is still difficult and prophylactic modalities seems mandatory but are yet to be defined. Standard therapy of invasive fungal infections relies on the administration of intravenous amphotericin B. This agent is difficult to administer and toxic. Recently, new antifungal agents have been developed and are currently under investigation. Those new agents included itraconazole and fluconazole as well as new galenic preparations of amphotericin B such as liposomes. All these studies should provide optimal management of invasive fungal infections and improve the prognosis of those patients.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Fluconazole; Humans; Itraconazole; Ketoconazole; Mycoses

We describe a patient with a 10-year history of rheumatoid arthritis who developed septic arthritis of the knee secondary to Candida albicans. Joint sterilization was obtained by debridement and 865 mg. of IV amphotericin B. We review 23 other cases of candidal arthritis in adults with specific reference to disease recognition and treatment.

Topics: Aged; Amphotericin B; Arthritis, Infectious; Arthritis, Rheumatoid; Candidiasis; Female; Humans; Knee Joint

We have presented the case of a postpartum woman with a pseudocyst infected with C albicans and have reviewed the relevant literature. The patient did well with surgical drainage of the pseudocyst and adjunctive therapy with amphotericin B. Candida species isolated from a pancreatic pseudocyst or abscess should be considered pathogens, and the patient should receive aggressive therapy.

Topics: Acute Disease; Adolescent; Amphotericin B; Candidiasis; Combined Modality Therapy; Female; Humans; Pancreatic Cyst; Pancreatic Pseudocyst; Puerperal Infection; Tomography, X-Ray Computed

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cryptococcosis; Drug Synergism; Drug Therapy, Combination; Flucytosine; Humans; Mycoses; Prospective Studies; Rifampin

C. albicans and its related species have become major nosocomial causes of morbidity and mortality in the immunocompromised and in other severely ill patients. Diagnosis of the severe forms of the disease remains difficult and depends on the basis of a composite of clinical findings. Treatment for most forms of severe Candida infections remains amphotericin B despite its toxicities. Until more effective prevention of the disease becomes feasible, Candida infections are likely to increase in frequency as major iatrogenic problems.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Candidiasis; Humans; Immune Tolerance; Opportunistic Infections

C tropicalis is a frequent and virulent pathogen in neutropenic patients. Infection control personnel should be familiar with this microorganism and the significance of a positive culture for C tropicalis in a setting of poor host resistance.

Topics: Amphotericin B; Candida; Candidiasis; Humans; Neutropenia; Opportunistic Infections

Systemic candidiasis is a disease of increasing incidence and proportions, which appears to be associated with the advances in modern medicine. It involves primarily patients with severe debilitating and malignant disease who are receiving immunosuppressive, cytotoxic, antimetabolite, and antibiotic therapy. Side effects of these otherwise major therapeutic agents predispose patients to opportunistic fungal infections, of which candidiasis is the most common. The high morbidity and mortality of disseminated candidiasis in neutropenic patients are difficult obstacles to obtaining the optimal, if not full, potential of modern chemotherapy for cancer. The inability to diagnose early invasive and systemic candidiasis is a major handicap that delays timely initiation of antifungal therapy. The paucity of highly efficacious antifungal agents with low toxicity severely limits the ability to successfully cure systemic fungal infections in cancer patients. Aggressive research into the basic biology of Candida spp. is necessary for directing the development of better diagnostic methods and improved antifungal drugs.

Topics: Amphotericin B; Candidiasis; Flucytosine; Humans; Immune Tolerance; Ketoconazole; Neoplasms; Opportunistic Infections; Risk Factors

The authors report a case of mycotic osteitis of the upper maxillary bone due to Candida Albicans occurring in a 56 year old female patient under treatment for chronic myeloid leukemia. The etiologically difficult diagnosis could only be confirmed after deep surgical biopsy with mycological study of a fragment. A review of the literature confirmed the rarity of upper maxillary involvement by Candida Albicans. Particularly when there is isolated involvement and no evidence of a distant primary focus. The differential diagnosis essentially includes centro-facial malignant granuloma.

Topics: Amphotericin B; Candidiasis; Diagnosis, Differential; Facial Bones; Female; Flucytosine; Granuloma, Lethal Midline; Humans; Immunologic Deficiency Syndromes; Middle Aged; Osteitis

Seven cases of successfully treated Candida albicans cerebrospinal fluid shunt infections are reported. Treatment consisted of shunt removal and intravenous Amphotericin B in all cases and intraventricular Amphotericin B in 4 cases. Serious underlying medical illness, recent antibiotic therapy, indwelling intravascular and/or Foley catheters, coincident candidiasis and low birth weight prematurity are major risk factors for candida shunt infection. Candida shunt infection appears to occur by either contamination at the time of shunt placement or by hematogenous dissemination.

Topics: Adolescent; Aged; Amphotericin B; Anti-Bacterial Agents; Candidiasis; Catheters, Indwelling; Cerebrospinal Fluid Shunts; Equipment Contamination; Female; Humans; Infant, Newborn; Infant, Premature; Male; Opportunistic Infections; Risk Factors; Sepsis; Surgical Wound Infection

Topics: Adult; Amphotericin B; Candidiasis; Child; Cystitis; Diagnosis, Differential; Humans; Infant, Newborn; Pyelonephritis; Therapeutic Irrigation; Urinary Catheterization

Candida pericarditis and tamponade developed in a patient with sterile purulent pericarditis secondary to systemic lupus erythematosus. Therapy with amphotericin B and properly timed surgical intervention led to a clinical and microbiological cure. This article emphasizes the importance of differentiating an infected pericardial effusion from the sterile pericarditis of systemic lupus erythematosus and provides suggested guidelines for the management of that complication.

Topics: Adolescent; Amphotericin B; Candidiasis; Cardiac Tamponade; Female; Humans; Lupus Erythematosus, Systemic; Pericardial Effusion; Pericarditis; Recurrence

Very low birth weight infants often have multiple predisposing conditions for the development of invasive candidiasis. In patients with systemic candidiasis, the kidney is vulnerable to the formation of cortical abscesses or obstructive intrarenal masses ("fungus balls"), usually at the ureteropelvic junction. Ureteropelvic junction obstructive fungal uropathy necessitates invasive debridement to restore renal function. A very low birth weight infant, infected with Candida, was first seen with hypertension, renal insufficiency, and urine cultures positive for fungus; obstructive bladder fungus ball was diagnosed by ultrasonography. Mechanical disruption with amphotericin B bladder irrigation was accomplished via ultrasonographic guidance, relieving renal obstruction and insufficiency. Systemic antifungal therapy was completed with amphotericin B and flucytosine. The first reported case of bladder obstructive fungal uropathy in a neonate is added to a review of 16 cases of neonatal renal obstructive uropathy.

Topics: Administration, Intravesical; Amphotericin B; Candidiasis; Humans; Hydronephrosis; Hypertension, Renal; Infant, Newborn; Infant, Premature, Diseases; Male; Ultrasonography; Urinary Bladder Diseases

A 31-year-old patient with sickle-cell disease who had previous cholecystectomy developed acute onset of jaundice and abdominal pain. An endoscopic retrograde cholangiography demonstrated multiple filling defects within the bile ducts. Microscopic examination of "calculi" removed at surgery revealed that a fungal ball composed of Candida was the cause of biliary obstruction in this case. The patient eventually recovered after removal of the fungal masses and intrabiliary instillation of amphotericin.

Topics: Adult; Amphotericin B; Anemia, Sickle Cell; Candidiasis; Cholangiopancreatography, Endoscopic Retrograde; Cholestasis; Combined Modality Therapy; Gallstones; Humans; Male; Prognosis

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Candidiasis; Humans; Lung Diseases, Fungal; Miconazole; Mucormycosis; Mycoses

Topics: Amphotericin B; Candida; Candidiasis; Catheters, Indwelling; Flucytosine; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Meningitis

We have recently treated three patients with Candida vertebral osteomyelitis. In each patient there was at least one characteristic prodromal condition, including trauma, multiple antibiotics following bowel surgery, and acute nonlymphocytic leukemia. All patients were treated successfully with amphotericin B. Based on our findings and a review of the literature, we would recommend a 1.0-1.2 gm total dosage of amphotericin B. Alternative therapeutic choices such as 5FC and/or ketoconazole, under specific clinical conditions, have been successfully employed. However, cure can best be confirmed by post-treatment biopsy.

Topics: Adult; Aged; Amphotericin B; Candidiasis; Humans; Lumbar Vertebrae; Male; Osteomyelitis; Spondylitis; Thoracic Vertebrae

Topics: Amphotericin B; Animals; Candidiasis; Drug Carriers; Emulsions; Excipients; Female; Hemolysis; Humans; Infusions, Parenteral; Lipids; Male; Mice; Rabbits; Tissue Distribution

Genitourinary fungal infections have become increasingly common in clinical practice. We review the literature on such infections, emphasizing recognition of fungal disease, predisposing factors, pathogenesis, and approaches to therapy.

Topics: Amphotericin B; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Female; Genital Diseases, Female; Genital Diseases, Male; Histoplasmosis; Humans; Infant, Newborn; Male; Mycoses; Urinary Tract Infections

The deep mycoses are increasing in importance both as opportunistic infections and from exposure in geographically defined areas. Diagnosis may be difficult in both groups. Mucosal involvement may be non-specific (e.g., in disseminated candidiasis) or highly predictive of disseminated disease (e.g., histoplasmosis, blastomycosis and paracoccidioidomycosis). Skin involvement is generally uncommon in disseminated aspergillosis, mucormycosis and cryptococcosis but is more common in candidemia and coccidioidomycosis. Manifestations of mucosal and cutaneous lesions of the deep mycoses are reviewed and the need for an aggressive diagnostic approach stressed. Culture is more specific than histopathologic examination alone but the latter may have to suffice in some cases. Control of underlying disease and administration of amphotericin B remain the mainstays of therapy. Ketoconazole is being evaluated as an alternative in therapy of some deep mycoses.

Topics: Amphotericin B; Aspergillosis; Blastomycosis; Candidiasis; Candidiasis, Cutaneous; Coccidioidomycosis; Cryptococcosis; Dermatomycoses; Flucytosine; Histoplasmosis; Humans; Immunosuppression Therapy; Ketoconazole; Miconazole; Mouth Diseases; Mouth Mucosa; Mucormycosis; Mycoses; Paracoccidioidomycosis; Sporotrichosis; Travel

As invasive fungal infection remains a common problem in the management of cancer patients, chemoprophylaxis of these opportunistic infections is desperately needed. The most frequently investigated antifungal agents have been nystatin, amphotericin B, and ketoconazole. In placebo-controlled studies, high doses of antifungal agents decreased the positive results from surveillance cultures, and there is some suggestion that such chemoprophylaxis may reduce the incidence of invasive candidiasis in neutropenic cancer patients. However, no oral chemoprophylaxis has effectively prevented aspergillosis or mucormycoses in these patients. There are still many areas of controversy, and the most adequate regimens, if any, remain to be defined.

Topics: Administration, Oral; Administration, Topical; Amphotericin B; Antifungal Agents; Candidiasis; Clinical Trials as Topic; Humans; Ketoconazole; Miconazole; Mycoses; Neoplasms; Nystatin

In the past 20 years, there has been a marked increase in the number of reported cases of meningitis and brain abscess due to fungi and yeasts. This increase is due in part to better diagnostic techniques and greater awareness of the possibility of fungal invasion of the nervous system; but the increase can also be attributed to a growing pool of severely compromised hosts, many of whom are undergoing treatment with adrenal glucocorticoids or immunosuppressive agents. The diagnosis and treatment of aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, infections caused by dematiaceous fungi, histoplasmosis, paracoccidioidomycosis, petriellidosis, and sporotrichosis, as well as relatively rare infections of the central nervous system caused by other fungi, are discussed. The efficacy of amphotericin B and 5-fluorocytosine in the treatment of CNS fungal and yeast infections is also evaluated.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Central Nervous System Diseases; Chromoblastomycosis; Cladosporium; Coccidioidomycosis; Cryptococcosis; Female; Fungi; Histoplasmosis; Humans; Male; Meningitis; Meningoencephalitis; Middle Aged; Mucormycosis; Mycoses; Paracoccidioidomycosis; Phialophora; Sporotrichosis

Infection is the major cause of morbidity and mortality in children receiving anticancer therapy. Children who have severe neutropenia (neutrophil count less than 100/mm3) for longer than 2 weeks should receive oral antibiotic prophylaxis. At present, trimethoprim sulfamethoxazole in combination with either nystatin or amphotericin B is the best regimen for reducing the incidence of serious infections. Trimethoprim sulfamethoxazole is very effective in the prevention of Pneumocystis carinii pneumonitis. Clinicans will have to balance the advantages and disadvantages of prophylaxis in patients who are at risk for P. carinii pneumonitis.

Topics: Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Child; Compliance; Drug Combinations; Humans; Leukemia; Neoplasms; Neutropenia; Nystatin; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Chromoblastomycosis; Coccidioidomycosis; Cryptococcosis; Flucytosine; Histoplasmosis; Humans; Imidazoles; Ketoconazole; Lung Diseases, Fungal; Miconazole; Mycoses; Nausea; Piperazines; Vomiting

The main antifungal agents used for deep-seated mycotic infections are the broad-spectrum antifungal drug amphotericin B, the narrow-spectrum agent flucytosine, and the newer broad-spectrum agents miconazole and ketoconazole. Amphotericin B remains the cornerstone of antifungal therapy. For the treatment of cryptococcal meningitis, the current recommendation is for the combined use of amphotericin B and flucytosine. 2-Hydroxystilbamidine is used only in indolent cases of blastomycosis; however, this condition is usually treated with amphotericin B. Clinical experience with the newer agents is limited. Not all patients from whom fungal agents have been isolated require treatment; the extent of the fungal infection should be determined, when possible, for evaluation of the need for treatment.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cryptococcosis; Flucytosine; Humans; Imidazoles; Mycoses; Stilbamidines

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Imidazoles; Mucormycosis; Mycoses; Prognosis

Fungal infections of the gastrointestinal tract have risen to higher levels of prevalence in the past decade. Major factors accounting for this increase are social changes, such as the increased ease and frequency of travel, which exposes the individual to environmental conditions that may result in fungal infection; increasing use of antibiotic and hormonal medications by otherwise healthy persons; and improved therapy for other diseases, such as polychemotherapy of cancer with its immunosuppressive effects. Both noninvasive and invasive fungal disease of the intestinal tract in otherwise healthy individuals can be successfully treated. The invasive fungal infections in patients with severe prior underlying disease are often first diagnosed postmortem, but improvement in serologic techniques now offers a possibility of earlier diagnosis and therapeutic intervention.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Diarrhea; Enteritis; Histoplasmosis; Humans; Imidazoles; Immunosuppression Therapy; Ketoconazole; Miconazole; Mycoses; Neoplasms; Nystatin; Paracoccidioidomycosis; Piperazines; Sulfadiazine

Topics: Amphotericin B; Animals; Candida albicans; Candidiasis; Cell Membrane; Cell Membrane Permeability; Chemical Phenomena; Chemistry; Chromatin; Dogs; Dose-Response Relationship, Drug; Drug Evaluation; Drug Evaluation, Preclinical; Humans; In Vitro Techniques; Kinetics; Mice; Microbial Sensitivity Tests; Mycoses; Neoplasms; Neoplasms, Experimental

Before 1950 no reliable or safe therapy existed for systemic and invasive mycoses, and only traditional and empirical topical preparations were available for dermatomycoses. Two distinct eras of rapid progress in antifungal therapy followed: first, in the 1950's came the introduction of the polyenes, nystatin and pimaricin for cutaneous, vaginal and intestinal candidiasis, and amphotericin B for the treatment of severe systemic mycoses. The second phase saw the successful introduction and clinical use of 5-fluorocytosine and several imidazole derivatives some twenty years later, at a time when the vast increase in iatrogenic systemic mycoses caused by opportunistic fungi had created an urgent and pressing need for new agents in addition to those still effective.

Topics: Amphotericin B; Antifungal Agents; Blastomycosis; Candidiasis; Flucytosine; Humans; Imidazoles; Mycoses; Natamycin; Nystatin; Polyenes

The incidence of genitourinary fungal infections is increasing, and because of their lethal potential, early diagnosis and treatment is mandatory. Candida is the most common urinary fungus and is manifest as renal involvement from systemic candidiasis, primary renal candidiasis, bezoar formation, cystitis, and as asymptomatic candiduria. The clinical status of the patient, serial urine cultures, excretory urogram, and serum candidal titers help to differentiate between the various disease states. Treatment is specific and is based on the clinical manifestation of the disease. Systemic candidiasis is treated with intravenous amphotericin. Fungal bezoars are best treated with oral flucytosine, ureteral and renal irrigation with amphotericin and, occasionally, operation. Cystitis is treated with oral flucytosine or amphoteric bladder irrigations. Asymptomatic candiduria is left untreated. A systematized evaluation and treatment regimen is presented.

Topics: Amphotericin B; Bezoars; Candidiasis; Flucytosine; Humans; Kidney Diseases; Urologic Diseases

Disseminated candidiasis has become an important infection, particularly in immunocompromised and postoperative patients. Although serologic tests may, in some settings, facilitate a premortem diagnosis, the disease is usually diagnosed by comprehensive clinical evaluation. Detection of the relatively newly recognized peripheral manifestations of candidemia may be vital to early diagnosis: endophthalmitis, osteomyelitis, arthritis, myocarditis, meningitis, and macronodular skin lesions. Studies in patients with chronic mucocutaneous candidiasis and in-vitro manipulations have begun to elucidate normal immune defense mechanisms against Candida, including serum factors, phagocytosis, intracellular killing mechanisms, and lymphocyte function (particularly T cell). The primary drugs for the treatment of disseminated candidiasis are still amphotericin B or amphotericin B plus 5-fluorocytosine; the mainstay of therapy for chronic mucocutaneous candidiasis is amphotericin B. Other antifungals and immune system-stimulating modalities (transfer factor, thymosin, thymus epithelial cell transplantation, and levamisol) may be useful for chronic mucocutaneous candidiasis in some settings and deserve further evaluation.

Topics: Amphotericin B; Animals; Antifungal Agents; Arthritis; Brain Diseases; Candidiasis; Candidiasis, Cutaneous; Drug Therapy, Combination; Endophthalmitis; Humans; Immunotherapy; Leukocytes; Lymphocytes; Macrophages; Myocarditis; Osteomyelitis; Phagocytosis; Skin Diseases

Flucytosine is a systemic antifungal drug that is readily absorbed from the gastrointestinal tract. The most clearly documented therapeutic effect has been in cryptococcosis, candidiasis, and chromomycosis. An important limitation of the use of flucytosine in all three diseases has been drug resistance arising during therapy. The addition of low-dose, intravenous amphotericin B to flucytosine therapy of cryptococcosis has appeared to decrease the frequency of secondary flucytosine resistance. In addition, the two drugs have an additive or slightly synergistic effect against flucytosine susceptible isolates of Cryptococcus and Candida. The combination is probably the treatment of choice in cryptococcal meningitis and offers promise in the therapy of systemic candidiasis and nonmeningeal cryptococcosis.

Topics: Amphotericin B; Candidiasis; Chromoblastomycosis; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Mycoses

Topics: Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; Candidiasis; Child; Child, Preschool; Female; Humans; Humerus; Infant; Infant, Newborn; Male; Middle Aged; Osteomyelitis; Pancytopenia; Ribs; Tibia

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candida; Candidiasis; Cryptococcosis; Humans; Lung Diseases, Fungal; Meningitis; Serologic Tests

Topics: Acute Disease; Adrenal Cortex Hormones; Amphotericin B; Aspergillosis; Blood Transfusion; Candidiasis; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Hodgkin Disease; Humans; Iron; Leukemia; Leukemia, Lymphoid; Lymphoma; Mucor; Multiple Myeloma; Mycoses; Neutropenia; Rhizopus

Topics: Amphotericin B; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Complement Fixation Tests; Cryptococcosis; Fluorouracil; Histoplasmosis; Humans; Lung Diseases, Fungal; Skin Tests; Stilbamidines

Seven patients with Candida meningitis are reported. These 7, plus 21 previously cited cases, were reviewed. This infection arose by two distinct mechanisms: hematogenous dissemination and direct inoculation. Recent antibiotic therapy, corticosteroid administration and severe underlying diseases were important predisposing factors. Fever, meningismus, elevated CSF pressures and localizing neurologic signs were commonly noted. Organisms were seen on gram-stain of CSF in only 43% of cases. Mortality rate in patients receiving inadequate or no antifungal therapy was high (greater than 90%), while those patients given appropriate antifungal drugs, especially intravenous amphotericin B, had a significantly lower mortality rate (38%). Several factors associated with poor prognosis were delineated in this study: diagnostic interval after symptomatic onset longer than two weeks, CSF glucose levels below 35 mg/100 ml and presence of intracranial hypertension and focal neurologic deficits.

Topics: Amphotericin B; Candidiasis; Cerebrospinal Fluid Shunts; Child, Preschool; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Meningitis; Middle Aged; Prognosis

Although fungal urinary tract infections occur less frequently than bacterial urinary tract infections their incidence has increased during the last several decades and their clinical importance to the urologist should not be underestimated. Herein the pertinent literature on fungal urinary tract infections is reviewed, with emphasis on the predisposing factors, pathogenesis, host defense mechanisms and the clinical spectrum of the disease. An approach to the evaluation of positive cultures and therapy is presented.

Topics: Amphotericin B; Animals; Candida; Candidiasis; Female; Flucytosine; Genital Diseases, Female; Genital Diseases, Male; Humans; Male; Mice; Mycoses; Urinary Tract Infections

On the basis of the data currently available, no dogmatic statements can be made about optimal therapy for Candida endocarditis. In those with valve protheses, early surgery should be carefully assessed even though the differences in outcome (17% vs 53% survival) are not yet statistically significant.

Topics: Adolescent; Amphotericin B; Aortic Valve; Candidiasis; Drug Therapy, Combination; Endocarditis; Flucytosine; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Nystatin; Tricuspid Valve

Effective antifungal therapy must be long-term, nondamaging, penetrating to the eye, and highly active against each patient's fungus. Results of antifungal sensitivity testing of 61 collected ocular fungal pathogens and observations in 25 cases treated with one of the nonpolyene antifungal drugs indicated that infection was rapidly controlled and eradicated with restoration of visual acuity, determined by the degree of disorganization present at the time of commencement of rational specific antifungal therapy. Pimaricin has the widest spectrum, a medium level of activity, and rather poor penetration but is recommended as an antifungal prophylactic and as first-line-therapy for ocular fungal disease while awaiting identification and sensitivity testing of the fungus. Flucytosine combined with amphotericin B, or possibly with clotrimazole or miconazole, is recommended for Candida infections. Clotrimazole is the drug of choice for Aspergillus species although miconazole and econazole are more effective with some isolates. Miconazole and econazole are recommended for miscellaneous filamentous fungi although clotrimazole or thiabendazole are superior in some cases. Each of these drugs may be useful in patients infected with Fusarium who do not respond to primaricin. In these cases, drug use should be guided by the results of antifungal sensitivity testing. In addition to medical antifungal therapy some eyes may require excisional keratoplasty with the lens removal and evacuation of the posterior chamber and anterior vitreous cavity.

Topics: Adrenal Cortex Hormones; Adult; Aged; Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus; Blindness; Candida; Candidiasis; Clotrimazole; Cornea; Eye Diseases; Female; Fusarium; Glaucoma; Humans; Imidazoles; Male; Middle Aged; Mycoses; Natamycin; Polyenes

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Blastomycosis; Candicidin; Candidiasis; Coccidioidomycosis; Colistin; Cryptococcosis; Dermatomycoses; Drug Resistance, Microbial; Emetine; Flucytosine; Griseofulvin; Histoplasmosis; Humans; Imidazoles; Minocycline; Natamycin; Nystatin; Polyenes; Tolnaftate

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Age Factors; Aged; Amphotericin B; Anti-Bacterial Agents; Candidiasis; Child; Child, Preschool; Endophthalmitis; Eye; Female; Humans; Immunosuppressive Agents; Infant; Infusions, Parenteral; Male; Middle Aged; Postoperative Complications; Racial Groups; Sepsis; Sex Factors

Topics: Amphotericin B; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Burns; Candida albicans; Candidiasis; Catheterization; Central Nervous System Diseases; Diabetes Complications; Diagnosis, Differential; Fluorescent Antibody Technique; Fluorouracil; Hemagglutination Inhibition Tests; Humans; Hydrogen-Ion Concentration; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Lung Diseases, Fungal; Nystatin; Pneumonia, Pneumocystis; Pyelonephritis; Respiratory Hypersensitivity; Sepsis; Serologic Tests

Topics: Amphotericin B; Brain Diseases; Candidiasis; Coccidioidomycosis; Cryptococcosis; Herpes Zoster; Humans; Immunity, Cellular; Immunity, Maternally-Acquired; Leprosy; Lymphocyte Activation; Lymphokines; Male; Meningitis; Middle Aged; Subacute Sclerosing Panencephalitis; T-Lymphocytes; Tuberculosis; Wiskott-Aldrich Syndrome

Topics: Amphotericin B; Candida; Candidiasis; Candidiasis, Cutaneous; Candidiasis, Oral; Candidiasis, Vulvovaginal; Cheilitis; Female; Folliculitis; Gastrointestinal Diseases; Humans; Immunologic Deficiency Syndromes; Intertrigo; Leukoplakia, Oral; Male; Nystatin; Paronychia

Topics: Administration, Topical; Amphotericin B; Candidiasis; Coccidioides; Flucytosine; Fusarium; Griseofulvin; Histoplasma; Humans; Mycoses; Natamycin; Nystatin; Streptomyces

Topics: Amphotericin B; Benzene Derivatives; Benzyl Compounds; Candidiasis; Drug Interactions; Ethers; Griseofulvin; Humans; Imidazoles; Nystatin; Tolnaftate

Topics: Actinomycosis; Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Flucytosine; Histoplasmosis; Humans; Mucormycosis; Mycoses; Nocardia Infections; Sporotrichosis

Topics: Adolescent; Adult; Amphotericin B; Animals; Autoantibodies; Blood Transfusion; Candidiasis; Candidiasis, Cutaneous; Child; Endocrine System Diseases; Female; Foot Dermatoses; Hand Dermatoses; Humans; Immunity; Immunity, Cellular; Lymphocyte Activation; Macrophages; Male; Mucous Membrane; Nails; Skin

Topics: Amphotericin B; Candida; Candidiasis; Female; Humans; Male; Urethra; Urethritis

Topics: Amphotericin B; Aspergillosis; Candida; Candidiasis; Child; Child, Preschool; Coccidioidomycosis; Coccidiosis; Cryptococcosis; Endocarditis; Granuloma; Histoplasmosis; Humans; Infant; Kidney; Kidney Function Tests; Meningitis; Mycoses; Pneumonia

Topics: Adult; Amphotericin B; Candidiasis; Female; Gastrointestinal Diseases; Histoplasmosis; Humans; Infant; Leukemia; Lymphoma; Male; Mucormycosis; Mycoses; Nystatin

Topics: Actinomycosis; Adolescent; Adult; Amphotericin B; Animals; Aspergillosis; Basidiomycota; Blastomycosis; Candidiasis; Cephalosporins; Child; Chromoblastomycosis; Coccidioidomycosis; Conjunctiva; Cryptococcosis; Drug Synergism; Eye Diseases; Female; Fungi; Geotrichosis; Guinea Pigs; Histoplasmosis; Humans; Male; Mucor; Mycetoma; Mycoses; Natamycin; Nystatin; Penicillium; Pityriasis; Rabbits; Rhinosporidiosis; Sporotrichosis; Tinea

Topics: Amphotericin B; Candidiasis; Child; Humans; Lung Diseases, Fungal

Topics: Actinomycosis; Amphotericin B; Aspergillosis; Biopsy; Blastomycosis; Candidiasis; Cystoscopy; Humans; Mycoses; Penicillins; Penicillium; Sporothrix; Surgical Procedures, Operative; United States; Urinary Tract Infections; Urography

Topics: Actinomycosis; Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Candidiasis; Cryptococcosis; Griseofulvin; Histoplasmosis; Humans; Nystatin; Penicillins

Topics: Actinomycosis; Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Griseofulvin; Histoplasmosis; Humans; Iodides; Mucormycosis; Mycoses; Nocardia Infections; Nystatin; Penicillins; Sporotrichosis; Stilbamidines; Sulfadiazine; Surgical Procedures, Operative; Toxicology

Intra-abdominal candidiasis (IAC) has a high mortality rate. However, the correct management of a critically ill patient with suspected IAC remains unclear. The aim of this study was to evaluate the safety of pulsed high-dose liposomal amphotericin B (L-AmB) in patients with suspected IAC managed with a beta-D-glucan (BDG)-guided strategy.. This phase 2 prospective study enrolled adult patients with intra-abdominal sepsis following surgery. Patients received a single dose of L-AmB 5 mg/kg on day 1. On day 3, L-AmB was discontinued in patients with a negative basal BDG result, and continued (3 mg/kg/daily) in patients with a positive basal BDG result or microbiologically confirmed IAC. The primary endpoint was the occurrence of adverse events, defined using the Common Toxicity Criteria classification.. In total, 40 patients were enrolled from January 2019 to August 2022. Fifteen (37.5%) patients were male, and the median age was 65 [interquartile range (IQR) 49-76] years. Thirty-one (77.5%) patients underwent urgent surgery, and the principal indication was secondary/tertiary peritonitis (n=22, 55%); half of the patients had undergone a previous surgical operation within the preceding 30 days. Five (12.5%) patients met the criteria for septic shock at enrolment. The median APACHE II score on admission to the intensive care unit was 12 (IQR 10-15). IAC was excluded in 33 (85%) patients, but IAC was probable and proven in five (12.5%) and two (5%) patients, respectively. The single dose of L-AmB 5 mg/kg was well tolerated in all patients, and no early or late severe adverse events related to the drug were reported. L-AmB was discontinued in 65% of patients following a negative basal BDG result. The all-cause 30-day mortality rate was 15%, and no deaths were related to L-AmB administration or uncontrolled IAC. The mortality rates for patients with and without proven IAC were 0% and 15.8%, respectively (P=0.99).. The rate of proven IAC among critically ill high-risk patients was low (5%). A single dose of L-AmB 5 mg/kg, with prompt withdrawal in the case of a basal negative BDG result, seems to be a safe and effective approach in this population.

Topics: Adult; Aged; Antifungal Agents; Candidiasis; Critical Illness; Female; Humans; Male; Middle Aged; Peritonitis; Prospective Studies

Candida albicans causes debilitating, often azole-resistant, infections in patients with chronic mucocutaneous candidiasis (CMC). Amphotericin B (AMB) resistance is rare, but AMB use is limited by parenteral administration and nephrotoxicity. In this study, we evaluated cochleated AMB (CAMB), a new oral AMB formulation, in mouse models of oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC) and in patients with azole-resistant CMC. OPC and VVC were modeled in

Topics: Amphotericin B; Animals; Antifungal Agents; Azoles; Candida albicans; Candidiasis; Candidiasis, Chronic Mucocutaneous; Candidiasis, Oral; Candidiasis, Vulvovaginal; Female; Humans; Mice

The aim of this study was to evaluate micafungin efficacy for treatment of invasive candidiasis/candidaemia in patients with cancer. Modified intent-to-treat populations were analysed from two trials: one, in adults and children with confirmed Candida infection, compared micafungin (adults 100 mg day(-1); children 2 mg kg(-1) day(-1)) with liposomal amphotericin B (L-AmB 3 mg kg(-1) day(-1)); and the other, in adults only, compared micafungin (100 or 150 mg day(-1)) with caspofungin (50 mg day(-1); 70 mg loading dose). Primary efficacy endpoint in both trials was treatment success, defined as both clinical and mycological response at end of therapy. In the micafungin/L-AmB trial, 183/489 patients had malignancy (37% neutropenic). In the micafungin/caspofungin trial, 176/572 patients had malignancy (26% neutropenic). Micafungin treatment success rates were generally similar in patients with/without malignancy and to rates observed with L-AmB and caspofungin. Most patients with malignancy and neutropenia were successfully treated by all three drugs. For all drugs, incidence of discontinuations because of treatment-related adverse events was similar for patients with malignancy (≤7.7%) vs. no malignancy (≤8.0%). These results suggest that compared with L-AmB and caspofungin, micafungin was effective and well tolerated in patients with candidiasis/candidaemia with/without malignancy. Further prospective trials are recommended to evaluate comparative outcomes with a primary focus on patients with malignancies and invasive candidiasis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Child; Child, Preschool; Double-Blind Method; Echinocandins; Female; Humans; Infant; Infant, Newborn; Lipopeptides; Male; Micafungin; Middle Aged; Neoplasms; Treatment Outcome; Young Adult

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Critical Illness; Humans; Middle Aged; Pilot Projects; Treatment Outcome

Crude and attributable mortality rates in patients with candidemia and invasive candidiasis remain unacceptably high. It is important to reach a more complete understanding of the risk factors underlying poor outcomes in patients with invasive Candida infections. Micafungin therapy has been assessed in two phase 3 trials compared to either liposomal amphotericin B or caspofungin. The availability of this large dataset allows the analyses of non-drug factors associated with survival and treatment success. A multivariate regression analysis was performed on data from the two trials separately and as a pooled analysis (N = 1,070). Analysis outcomes were survival at 42 days post-initiation of therapy and treatment success. For the pooled analysis, treatment success was significantly more likely for candidemia than invasive candidiasis. Both survival and treatment success were significantly less likely for the non-removal of catheter versus removal, Asian-Indians versus Caucasians, APACHE II score >20 to 30 versus or=70 years versus <50 years, baseline corticosteroids, and persistent neutropenia. Survival was also significantly less likely for treatment in other regions versus North America and for patients with renal failure at baseline. These findings help to define non-antifungal drug factors that may impact survival and treatment success in invasive candidiasis or candidemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; APACHE; Candidiasis; Catheterization; Echinocandins; Female; Fungemia; Humans; Lipopeptides; Male; Micafungin; Middle Aged; North America; Prospective Studies; Racial Groups; Survival Analysis; Treatment Outcome; Young Adult

Invasive fungal infections (IFIs) are major complications after allogeneic hematopoietic SCT (HSCT). PCR-based assays able to detect fungal DNA have been reported to precede clinical diagnosis of IFI. We performed a prospective study to evaluate a PCR-based pre-emptive approach. Ninety-nine patients undergoing reduced-intensity conditioning (RIC) HSCT were followed with fungal PCR during the first 100 days post transplantation. Patients who tested positive were randomized to receive liposomal amphotericin B, or to no intervention. After day 100, PCR tests were performed only on clinical suspicion of IFI. A single positive PCR test was not associated with IFI, irrespective of treatment. After day 100, PCR tests for Aspergillus did not contribute to diagnosis of invasive aspergillosis (IA). The cumulative incidence rates of proven or probable IA during the first year after transplantation were 9%. GVHD grades II-IV (P=0.0014), CMV-seronegative recipient with CMV-seropositive donor (P0.001), and conditioning with alemtuzumab (P=0.014) were significant risk factors for developing IA in a multivariate model. In this study, PCR on peripheral blood was a poor indicator of IFI early after RIC HSCT. Aspergillus PCR tests performed on clinical suspicion after day 100 were insufficiently sensitive to be diagnostically useful.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Candida; Candidiasis; Child; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Mycoses; Polymerase Chain Reaction; Prospective Studies; Risk Factors; Treatment Outcome; Young Adult

This study was conducted to evaluate once-weekly liposomal amphotericin B (L-AmB) for Candida prophylaxis in very low birth weight (VLBW) neonates.. This prospective, randomized, open-label, placebo-controlled study included neonates who were <32 weeks' gestational age, <7 days old, and weighing <1500 g at birth. Subjects were randomized to receive L-AmB 5 mg/kg per week or placebo (dextrose water) and were followed until 6 weeks of age. Surveillance cultures were obtained at baseline, at 72 hours, and weekly thereafter. Study drug was continued until 6 weeks after birth or the discontinuation of high-risk treatments and invasive devices, whichever occurred first. Blood cultures were obtained as clinically indicated. The primary end point was development of Candida colonization by 6 weeks' postnatal age; secondary end points included development of invasive candidiasis and occurrence of treatment-related adverse events. Safety variables included renal and hepatic function tests, incidence of grade III-IV intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC), and mortality.. Forty subjects were enrolled and randomized to receive L-AmB (12 males, 8 females; 50% white) or placebo (12 males, 8 females; 35% white). Subjects were evenly distributed by gestational age, age at enrollment, birth weight, race, and sex. Consent was withdrawn after completion of study treatment in 1 subject (L-AmB); 1 subject in each study arm died during the study; and 3 subjects were transferred back to their referring institutions (1 L-AmB, 2 placebo). Thus, 17 subjects in each arm completed all study procedures, although all 40 subjects were evaluable. Colonization before administration of study drug was noted in 4 L-AmB subjects (20%) and 1 placebo subject (5%); 1 (5%) and 3 (15%) subjects in the respective groups developed colonization while receiving study drug. No L-AmB subjects and 1 placebo subject developed candidiasis. One subject in each group died; these deaths were not considered related to study drug or fungal infection. There were no clinical differences between groups in the incidence of grade III-IV IVH, NEC, hypokalemia, nephrotoxicity, need for platelet or packed red blood cell transfusion, or mortality.. L-AmB 5 mg/kg once weekly was generally well tolerated in these VLBW infants. The data did not allow evaluation of efficacy. A larger, multicenter, randomized clinical trial of L-AmB for Candida prophylaxis that is appropriately powered is warranted.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Drug Administration Schedule; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Pilot Projects; Prospective Studies; Treatment Outcome

Antifungal prophylaxis for liver transplant recipients (LTRs) is common among patients considered at high risk of infection, but optimal prophylaxis duration and drug has not been defined. This study aimed to assess the effects of 14 days of antifungal therapy prophylaxis in reducing proven invasive fungal infections (IFI) in high-risk subjects. Eligible subjects who met 2 or more risk criteria were randomized 1:1 to the treatment arms (liposomal amphotericin B or fluconazole) and were followed for 100 days post transplantation for evidence of IFI. The study was designed to enroll 300 subjects, but was closed early for insufficient enrollment. A total of 71 subjects were enrolled and randomized. Two-thirds of subjects completed 14 days of study therapy. Ten subjects developed proven or probable IFI with Candida species (9 subjects) and Cryptococcus neoformans (1 subject); rates were similar in the 2 treatment arms. Eleven subjects died, but no death was attributed to study drug or IFI. In summary, high-risk LTRs tolerated antifungal prophylaxis well, and rates of IFI were lower than previously reported in untreated high-risk LTRs.

Topics: Adult; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Candida; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Double-Blind Method; Female; Humans; Incidence; Liver Transplantation; Male; Middle Aged; Mycoses; Treatment Outcome

Esophagitis is an important side effect in thoracic radiotherapy, no preventive drug therapy has been established yet. The aim of the present study was to prospectively evaluate the effectiveness of prophylactic antimycotic treatment with amphotericin B lozengers.. 40 consecutive patients with high-dose thoracic radiotherapy for lung cancer were investigated in a nonrandomized study. 20 patients receiving a median maximal esophageal dose of 67 Gy (range 61-80 Gy) were treated with amphotericin B lozengers four times daily from day 8 to the end of radiotherapy. Another 20 patients with a lower median maximal esophageal dose of 60 Gy (range 51-67.5 Gy) constituted the control group. Length of the irradiated esophagus and dose-length indices were evaluated. Side effects were prospectively scored according to the RTOG/EORTC criteria. There was a trend toward higher esophageal volumes in the prophylaxis group; furthermore, patients in this group were older, had a worse median Karnofsky Index and had more often received induction chemotherapy.. In the prophylaxis group, 15 patients remained free from esophagitis and five patients developed esophagitis grade 1. In the control group, four patients remained free from symptoms, 14 patients showed esophagitis grade 1 and two patients grade 2. The difference between the two groups was statistically significant (p < 0.05). The start of symptoms was delayed in the prophylaxis group in comparison to the control group: day 21 (median, range 14-44) and day 18 (median, range 10-32) respectively. Amphotericin B lozengers were tolerated without side effects by all patients.. Prophylactic administration of amphotericin B lozengers seems to effectively prevent radiation-induced esophagitis.

Topics: Administration, Oral; Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Esophagitis; Esophagus; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Radiation Injuries; Radiotherapy, High-Energy

Invasive candidiasis and candidemia are life-threatening nosocomial infections in intensive care patients.. A post hoc analysis of a phase 3 trial assessing micafungin (100 mg/day for subjects > 40 kg; 2 mg/kg/day for subjects

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Cross Infection; Echinocandins; Female; Humans; Intensive Care Units; Lipopeptides; Male; Micafungin; Middle Aged; Multivariate Analysis

Invasive candidiasis is increasingly prevalent in premature infants and seriously ill children, and pediatric data on available antifungal therapies are lacking.. We conducted a pediatric substudy as part of a double-blind, randomized, multinational trial to compare micafungin (2 mg/kg) with liposomal amphotericin B (3 mg/kg) as first-line treatment of invasive candidiasis. Treatment success was defined as clinical and mycologic response at the end of therapy. Statistical analyses were descriptive, as the sample size meant that the study was not powered for hypothesis testing.. One hundred six patients were included in the intent-to-treat population; and 98 patients-48 patients in the micafungin group and 50 patients in the liposomal amphotericin B group-in the modified intent-to-treat population. Baseline characteristics were balanced between treatment groups. Overall, 57 patients were <2 years old including 19 patients who were premature at birth; and 41 patients were 2 to <16 years old. Most patients (91/98, 92.9%) had candidemia, and 7/98 (7.1%) patients had other forms of invasive candidiasis. Treatment success was observed for 35/48 (72.9%) patients treated with micafungin and 38/50 (76.0%) patients treated with liposomal amphotericin B. The difference in proportions adjusted for neutropenic status was -2.4% [95% CI: (-20.1 to 15.3)]. Efficacy findings were consistent, independent of the neutropenic status, the age of the patient, and whether the patient was premature at birth. Both treatments were well tolerated, but with a lower incidence of adverse events that led to discontinuation in the micafungin group (2/52, 3.8%) compared with the liposomal amphotericin B group (9/54, 16.7%) (P = 0.05, Fisher exact test).. Micafungin seems to be similarly effective and as safe as liposomal amphotericin B for the treatment of invasive candidiasis in pediatric patients. (ClinicalTrials.gov number, NCT00106288).

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Double-Blind Method; Echinocandins; Humans; Infant; Infant, Newborn; Infant, Premature; Lipopeptides; Lipoproteins; Micafungin; Treatment Outcome

Invasive candidosis is increasingly prevalent in seriously ill patients. Our aim was to compare micafungin with liposomal amphotericin B for the treatment of adult patients with candidaemia or invasive candidosis.. We did a double-blind, randomised, multinational non-inferiority study to compare micafungin (100 mg/day) with liposomal amphotericin B (3 mg/kg per day) as first-line treatment of candidaemia and invasive candidosis. The primary endpoint was treatment success, defined as both a clinical and a mycological response at the end of treatment. Primary analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, number NCT00106288.. 264 individuals were randomly assigned to treatment with micafungin; 267 were randomly assigned to receive liposomal amphotericin B. 202 individuals in the micafungin group and 190 in the liposomal amphotericin B group were included in the per-protocol analyses. Treatment success was observed for 181 (89.6%) patients treated with micafungin and 170 (89.5%) patients treated with liposomal amphotericin B. The difference in proportions, after stratification by neutropenic status at baseline, was 0.7% (95% CI -5.3 to 6.7). Efficacy was independent of the Candida spp and primary site of infection, as well as neutropenic status, APACHE II score, and whether a catheter was removed or replaced during the study. There were fewer treatment-related adverse events--including those that were serious or led to treatment discontinuation--with micafungin than there were with liposomal amphotericin B.. Micafungin was as effective as--and caused fewer adverse events than--liposomal amphotericin B as first-line treatment of candidaemia and invasive candidosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; APACHE; Candidiasis; Double-Blind Method; Echinocandins; Female; Humans; Lipopeptides; Lipoproteins; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Peptides, Cyclic; Treatment Outcome

We retrospectively analyzed the antifungal usage in children with acute myeloid leukemia (AML). Overall, 211 of 304 patients (69.4%) received a total of 389 antifungal treatment episodes. In 234 episodes, initial antifungal treatment consisted of amphotericin B [as monotherapy, n = 193; median dosage (range) of amphotericin B deoxycholate 0.6 mg/kg per day (0.02-1.5 mg/kg per day) and of liposomal amphotericin B 3.0 mg/kg per day (0.6-30 mg/kg per day)], in 149 episodes of fluconazole [as monotherapy, n = 143; 5 mg/kg per day (1-29 mg/kg per day)], in 40 of flucytosine [as monotherapy, n = 1; 150 mg/kg per day (40-370 mg/kg per day)], and in 9 of itraconazole [as monotherapy, n = 8; 6 mg/kg per day (1.6-20 mg/kg per day)]. We conclude that the majority of children with AML receives at least one episode of antifungal therapy. Inappropriate dosing and combination of antimycotics need to be addressed in future educational measures.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Child; Female; Fluconazole; Flucytosine; Humans; Infant; Infant, Newborn; Itraconazole; Leukemia, Myelomonocytic, Acute; Male; Retrospective Studies

Amphotericin B is considered the treatment of choice for systemic candidiasis, but adverse effects may limit its use. An alternative option for the treatment of candidiasis includes lipid preparations of amphotericin B. This study investigated the safety and efficacy of AmBisome, a lipid formulation of amphotericin B containing liposomal structures, for the treatment of systemic candidiasis in very low birth weight infants (VLBWI).. Data from 26 VLBWI treated with AmBisome in the study group (AmBisome group) from October 2003 to July 2006 were compared with data from 20 VLBWI treated with amphotericin B as a historical control (Amphotericin group). This study was a prospective, historical control, multi-center trial.. Candida spp. was isolated in 73% (19/26) of the cases for the AmBisome group and 90% (18/20) of the cases for the Amphotericin group. The fungal eradication rate and the time to eradication was 84% (16/19) and 9+/-8 days in the AmBisome group, and 89% (16/18) and 10+/-9 days in the Amphotericin group, respectively (p=0.680 vs p=0.712). The major adverse effects were lower in the AmBisome group (renal toxicity, 21% vs 55%, p=0.029; hepatotoxity, 25% vs 65%, p=0.014, AmBisome group vs Amphotericin group, respectively). There was no significant difference in mortality attributed to systemic candidiasis (12% in the AmBisome group, 10% in the Amphotericin group, p=0.868).. AmBisome is effective and safe for treating systemic fungal infections in VLBWI.

Topics: Amphotericin B; Candidiasis; Female; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Male

Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species.. A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10.. Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P<.001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P<.001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P<.001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated.. Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.

Topics: Adult; Aged; Amphotericin B; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antifungal Agents; Candida; Candidiasis; Double-Blind Method; Female; HSP90 Heat-Shock Proteins; Humans; Male; Middle Aged; Patient Selection; Placebos; Recombinant Proteins; Treatment Outcome

We performed a prospective, randomized, open-label trial to evaluate the efficacy of low-dose liposomal amphotericin B (L-AmB) to reduce the incidence of invasive fungal infections (IFI) in patients with hematological malignancies and prolonged neutropenia (>10 days) following intensive chemotherapy.. In 219 neutropenic episodes (NE) of 132 patients randomization was performed. Patients received either 50 mg L-AmB every other day (arm A) or no systemic antifungal prophylaxis (arm B).. In the first NE of each patient the incidence of proven or probable IFI (primary end point) was five of 75 patients (6.7%) in arm A and 20 of 57 patients (35%) in arm B (P=0.001). Invasive aspergillosis occurred less frequently in patients receiving L-AmB-prophylaxis (P=0.0057), whereas the reduction of invasive candidiasis did not reach statistical significance (P=0.0655). In all NE the incidence of IFI was five of 110 NE (4.6%) in arm A versus 22 of 109 NE (20.2%) in arm B (P<0.01). Adverse events, possibly related to L-AmB, were observed in five NE (4.6%) and L-AmB was discontinued in three NE (2.8%). No grade 3 or 4 toxicities were observed.. Antifungal prophylaxis with low-dose L-AmB proved to be feasible and effective in our trial.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Female; Hematologic Neoplasms; Humans; Injections, Intravenous; Male; Middle Aged; Neutropenia

The usefulness to diagnose and monitor invasive candidiasis (IC) using beta-glucan (BG) and antibodies against Candida albicans germ tubes (CAGT) was evaluated in a twice-weekly screening of 35 episodes in neutropenic adults at high risk. Three proven IC and three probable IC were assessed. Diagnostic levels of both markers were detected in 100% of proven IC and in 66% of probable IC. Sensitivity, specificity, positive and negative predictive values of BG and anti-CAGT antibodies detection were 83.3%, 89.6%, 62.5% and 96.3%, and 83.3%, 86.2%, 55.5%, 96.1%, respectively. False positive reactions occurred at a rate of 10.3% and 13.8% for the detection of BG and anti-CAGT antibodies, respectively. However, the patients with false positive results were different by each test. Both tests anticipated the clinical and radiological diagnosis, and the initiation of antifungal therapy in most patients. Combination of both tests improved specificity and positive predictive value to 100%.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anemia, Aplastic; Antibodies, Fungal; Antibody Specificity; Antifungal Agents; Antigens, Fungal; beta-Glucans; Candida albicans; Candidiasis; False Positive Reactions; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Hepatitis; Humans; Liposomes; Male; Middle Aged; Neutropenia; Patient Isolation; Predictive Value of Tests; Sensitivity and Specificity

Invasive candidiasis is a common and serious complication of cancer and its therapy.. We retrospectively identified patients with malignancies enrolled in a double-blind randomized trial of caspofungin (50 mg/day after a 70 mg loading dose) vs. conventional amphotericin B (0.6-1.0 mg/kg/day) as treatment of documented invasive candidiasis. A favorable response required complete resolution of signs and symptoms plus eradication of the Candida pathogen(s). The primary efficacy analysis used a modified intention-to-treat (MITT) approach that included all patients with a confirmed diagnosis of invasive candidiasis who received > or =1 dose of study medication.. 74/224 (33%) patients in the MITT population had active malignancies. 25/30 (83%) hematological malignancies were acute or chronic leukaemias. 22/44 (50%) solid tumors were related to the gastrointestinal tract. Patients with hematological malignancies tended to be younger (median [range] age: 49 [19-74] vs. 59 [19-81] years) and have higher baseline acute physiology and chronic health evaluation (APACHE) II scores (mean [range]: 17 [0-28] vs. 15 [5-35]) than patients with solid tumors. Neutropenia [< or =500/microl] was present on entry in 23 (77%) patients with hematological malignancies and in one (3%) patient with a solid tumor. Candidemia was demonstrated in 56 (88%) cancer patients. C. albicans was the single most frequent isolate in cancer patients, although the majority of cases were caused by non-albicans species. Cancer patients in the caspofungin arm had more hematological malignancies (55 vs. 29%), higher baseline APACHE II scores (>20 in 36 vs. 15%), more frequent neutropenia (42 vs. 24%), and less C. albicans infections (27 vs. 49%) than the amphotericin B-treated cancer patients. Favorable response rates were 11/18 (61%) and 6/12 (50%) for patients with hematological malignancies treated with caspofungin or amphotericin B, respectively; the corresponding outcomes in patients with solid tumors were 12/15 (80%) and 17/29 (59%) for the 2 treatment arms. 7/14 (50%) caspofungin- and 4/10 (40%) amphotericin B-treated patients who were neutropenic on entry responded favorably. All-cause mortality rates during the study for caspofungin recipients were 11/18 (61%) with hematological malignancies and 6/15 (40%) with solid tumors, and for amphotericin recipients were 4/12 (33%) with hematological malignancies and 6/29 (21%) with solid tumors.. Underlying cancers, most commonly leukaemias and gastrointestinal tumors, were present in one-third of patients enrolled in this study of invasive candidiasis. Overall, 70% of caspofungin-treated and 56% of amphotericin B-treated cancer patients responded favorably. Response rates were lower for neutropenic leukaemic patients than for non-neutropenic patients with solid tumors in both treatment groups.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Echinocandins; Female; Fungemia; Gastrointestinal Neoplasms; Hematologic Neoplasms; Humans; Leukemia; Lipopeptides; Male; Middle Aged; Neoplasms; Neutropenia; Peptides, Cyclic; Retrospective Studies; Species Specificity; United States

The pharmacokinetics of amphotericin B lipid complex (ABLC) were investigated in neonates with invasive candidiasis enrolled in a phase II multicenter trial. Sparse blood (153 samples; 1 to 9 per patient, 1 to 254 h after the dose) and random urine and cerebrospinal fluid (CSF) samples of 28 neonates (median weight [WT], 1.06 kg; range, 0.48 to 4.9 kg; median gestational age, 27 weeks; range, 24 to 41 weeks) were analyzed. Patients received intravenous ABLC at 2.5 (n = 15) or 5 (n = 13) mg/kg of body weight once a day over 1 or 2 h, respectively, for a median of 21 days (range, 4 to 47 days). Concentrations of amphotericin B were quantified as total drug by high-performance liquid chromatography. Blood data for time after dose (TAD) of <24 h fitted best to a one-compartment model with an additive-error model for residual variability, WT0.75 (where 0.75 is an exponent) as a covariate of clearance (CL), and WT as a covariate of volume of distribution (V). Prior amphotericin B, postnatal age, and gestational age did not further improve the model. The final model equations were CL (liters/h) = 0.399 x WT(0.75) (interindividual variability, 35%) and V (liters) = 10.5 x WT (interindividual variability, 43%). Noncompartmental analysis of pooled data with a TAD of >24 h revealed a terminal half-life of 395 h. Mean concentrations in the urine after 1, 2, and 3 weeks ranged from 0.082 to 0.430 microg/ml, and those in CSF ranged from undetectable to 0.074 microg/ml. The disposition of ABLC in neonates was similar to that observed in other age groups: weight was the only factor that influenced clearance. Based on these results and previously published safety and efficacy data, we recommend a daily dosage between 2.5 and 5.0 mg/kg for treatment of invasive Candida infections in neonates.

Topics: Amphotericin B; Anti-Infective Agents; Candida; Candidiasis; Drug Combinations; Humans; Infant, Newborn; Models, Biological; Phosphatidylcholines; Phosphatidylglycerols

To investigate whether cytochrome P450-dependent enzymes are influenced by amphotericin B (Am-B) during the treatment of Candida oesophagitis in HIV-infected patients.. Twelve HIV-infected, antiretroviral-naive patients (CDC/WHO stage C3) with Candida oesophagitits were enrolled into a prospective clinical trial. The patients were treated with Am-B (0.4 mg/kg body weight) for two weeks. At baseline and after Am-B therapy the clearance of antipyrine and its metabolites were investigated by high-performance liquid chromatography. In addition, the urinary excretion of 6-beta-hydroxycortisol and 17-hydroxycorticosteroids was assessed by means of a radioimmunoassay.. The following significant changes were observed after Am-B treatment (P < 0.01): increase of antipyrine half-life (12.4 h vs 16.8 h) and the area under the plasma concentration-time curve (27.9 mg min/ml vs 38.1 mg min/ml); decrease of the total body clearance (61.2 ml/min vs 43.7 ml/min); decrease of the renal clearance of antipyrine metabolites - norantipyrine (7.45 ml/min vs 5.31 ml/min), 4-hydroxyantipyrine (15.4 ml/min vs 10.3 ml/min), hydroxymethylantipyrine (4.31 ml/min vs 3.65 ml/min); decrease of urinary 6-beta-hydroxycortisol excretion (453 microg/24h vs 298 microg/24h) and the ratio of 6-beta-hydroycortisol to 17-hydroxycorticosteroids (8.8% vs 6.4%).. Our data indicate that Am-B therapy has an inhibitory effect on cytochrome P450-dependent enzymes in HIV-infected patients. These results are of particular significance for HIV-infected patients who are concomitantly treated with drugs that are predominantly metabolised in the liver. A careful drug monitoring system seems advisable, especially for proteinase inhibitor experienced HIV-1-infected subjects.

Topics: 17-Hydroxycorticosteroids; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Bacterial Agents; Antipyrine; Candidiasis; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme System; Esophagitis; Humans; Hydrocortisone; Immunocompromised Host

A randomized, blinded, multicenter trial was conducted to compare fluconazole (800 mg per day) plus placebo with fluconazole plus amphotericin B (AmB) deoxycholate (0.7 mg/kg per day, with the placebo/AmB component given only for the first 5-6 days) as therapy for candidemia due to species other than Candida krusei in adults without neutropenia. A total of 219 patients met criteria for a modified intent-to-treat analysis. The groups were similar except that those who were treated with fluconazole plus placebo had a higher mean (+/- standard error) Acute Physiology and Chronic Health Evaluation II score (16.8+/-0.6 vs. 15.0+/-0.7; P=.039). Success rates on study day 30 by Kaplan-Meier time-to-failure analysis were 57% for fluconazole plus placebo and 69% for fluconazole plus AmB (P=.08). Overall success rates were 56% (60 of 107 patients) and 69% (77 of 112 patients; P=.043), respectively; the bloodstream infection failed to clear in 17% and 6% of subjects, respectively (P=.02). In nonneutropenic subjects, the combination of fluconazole plus AmB was not antagonistic compared with fluconazole alone, and the combination trended toward improved success and more-rapid clearance from the bloodstream.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Catheterization; Double-Blind Method; Drug Therapy, Combination; Female; Fluconazole; Fungemia; Humans; Male; Middle Aged; Neutropenia; Treatment Outcome

A liposomal amphotericin B preparation (L-AMP-LRC-1) has been developed and tested successfully in adults by us. This preparation was administered to 23 neonates with candidiasis in an open phase II study. All the 14 assessable patients responded completely to the L-AMP-LRC-1 therapy given at 1 mg/kg for 28 days. Compared to AmBisome, another liposomal formulation of amphotericin B, L-AMP-LRC-1 was effective at lower dose in neonatal candidiasis. Thus L-AMP-LRC-1 appears to be an effective and low cost drug for the treatment of candidiasis.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Female; Humans; Infant; Infant, Newborn; Liposomes; Male; Treatment Outcome

In a randomized study, caspofungin was compared with amphotericin B for the treatment of invasive candidiasis in a total of 239 adults from 56 sites in 20 countries. This study provided a unique opportunity to assess the frequency and outcome of invasive candidiasis caused by different Candida species worldwide, and the results are presented here. Efficacy was primarily assessed at the end of intravenous therapy using a modified intent-to-treat (MITT) analysis. This analysis was performed on 224 of the 239 patients enrolled in the study. Attempts were made to collect baseline Candida isolates from all patients for species identification at a central laboratory. Yeasts were identified to the species level using two commercial systems and microscopic examination. Viable baseline isolates were recovered from 210 of the 224 (94%) patients included in the MITT analysis. Candida albicans was the most frequently isolated species in all regions and was responsible for 45% of cases overall. Nevertheless, the majority of cases of infection were caused by non- albicans Candida species. In the USA and Canada, Candida glabrata was the second most commonly isolated pathogen (18%). In contrast, Candida parapsilosis and Candida tropicalis accounted for 55% of cases in Latin America. Outcomes were comparable for patients treated with caspofungin (74% overall; 64% and 80% for infections due to Candida albicans and non- albicans species) and amphotericin B (62% overall; 58% and 68% for infections due to Candida albicans and non- albicans species), and were generally similar across continents. The distribution of Candida species isolated from patients enrolled in a clinical trial may not be representative of pathogens causing invasive candidiasis in the general population. Nevertheless, our findings may affect the regional choice of empirical antifungal therapy for seriously ill patients with suspected or documented invasive candidiasis since different Candida species have varying susceptibility to conventional antifungal drugs.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Candida; Candidiasis; Caspofungin; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Echinocandins; Female; Follow-Up Studies; Fungemia; Humans; Incidence; International Cooperation; Lipopeptides; Male; Middle Aged; Peptides; Peptides, Cyclic; Risk Assessment; Severity of Illness Index; Treatment Outcome

We conducted a prospective, multicenter observational study of adults (n=1447) and children (n=144) with candidemia at tertiary care centers in the United States in parallel with a candidemia treatment trial that included nonneutropenic adults. Candida albicans was the most common bloodstream isolate recovered from adults and children (45% vs. 49%) and was associated with high mortality (47% among adults vs. 29% among children). Three-month survival was better among children than among adults (76% vs. 54%; P<.001). Most children received amphotericin B as initial therapy, whereas most adults received fluconazole. In adults, Candida parapsilosis fungemia was associated with lower mortality than was non-parapsilosis candidemia (24% vs. 46%; P<.001). Mortality was similar among subjects with Candida glabrata or non-glabrata candidemia; mortality was also similar among subjects with C. glabrata candidemia who received fluconazole rather than other antifungal therapy. Subjects in the observational cohort had higher Acute Physiology and Chronic Health Evaluation II scores than did participants in the clinical trial (18.6 vs. 16.1), which suggests that the former subjects are more often excluded from therapeutic trials.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Cohort Studies; Drug Administration Schedule; Female; Fluconazole; Fungemia; Humans; Infant; Male; Middle Aged; Prospective Studies; Survival Rate; United States

We assessed the impact of prophylaxis with the oral itraconazole solution and amphotericin B solution on fungal colonization and infection in a randomized study among patients with hematological malignancies and neutropenia. Infecting and colonizing Candida strains of patients suffering from candidiasis were genotyped by random amplification of polymorphic DNA (RAPD) analysis. A total of 106 patients were evaluated in this study: 52 patients in the itraconazole and 54 in the amphotericin B arm. During neutropenia fungal colonization in the oropharynx occurred in 11 (19.6%) and 24 (40.6%) and in the rectum in 11 (19.6%) and 23 (38.9%) courses in the itraconazole and amphotericin B groups ( P<0.05), respectively. Candida albicans was the most prevalent species in both study groups. Mixed fungal colonization with Candida krusei and Candida glabrata was increased in the amphotericin B group, yet without clinical importance since infections were due to C. albicans. The occurrence of invasive candidiasis was significantly increased in multicolonized compared to monocolonized patients. In the amphotericin B group 20 and in the itraconazole group 2 neutropenic patients showed multicolonization with Candida spp. ( P<0.05). Overall fungal infections were 3.8% in the itraconazole and 14.8% in the amphotericin B group ( P<0.05). RAPD typing showed oropharynx strains involved in superficial infections in four of five patients. In all four patients with deep fungal infections, it appears that the colonizing rectum strains were identical to infecting strains of Candida spp. Itraconazole solution significantly reduced Candida colonization and infection compared to amphotericin B solution. Most patients remained infected with the colonized strains for the entire study period, irrespective of antifungal prophylaxis.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Candida; Candidiasis; Genotype; Hematologic Neoplasms; Humans; Itraconazole; Neutropenia; Oropharynx; Random Amplified Polymorphic DNA Technique; Rectum

The echinocandins are large lipopeptide molecules that are inhibitors of beta-(1,3)-glucan synthesis, an action that damages fungal cell walls. In vitro and in vivo, the echinocandins are rapidly fungicidal against most Candida spp and fungistatic against Aspergillus spp. They are not active at clinically relevant concentrations against Zygomycetes, Cryptococcus neoformans, or Fusarium spp. No drug target is present in mammalian cells. The first of the class to be licensed was caspofungin, for refractory invasive aspergillosis (about 40% response rate) and the second was micafungin. Adverse events are generally mild, including (for caspofungin) local phlebitis, fever, abnormal liver function tests, and mild haemolysis. Poor absorption after oral administration limits use to the intravenous route. Dosing is once daily and drug interactions are few. The echinocandins are widely distributed in the body, and are metabolised by the liver. Results of studies of caspofungin in candidaemia and invasive candidiasis suggest equivalent efficacy to amphotericin B, with substantially fewer toxic effects. Absence of antagonism in combination with other antifungal drugs suggests that combination antifungal therapy could become a general feature of the echinocandins, particularly for invasive aspergillosis.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Caspofungin; Clinical Trials as Topic; Echinocandins; Fungal Proteins; Humans; Lipopeptides; Lipoproteins; Micafungin; Peptides; Peptides, Cyclic; Treatment Outcome

Studies in experimental animals and humans have shown that Amphotericin B (AmB) persists in urine for days to weeks after a single IV dose in levels that should inhibit candidal organisms and thereby obviate the need for frequent dosing. Including data from four previously described patients, we have now treated a total of 11 patients (12 episodes) with Candida urinary tract infections with single-dose AmB (six, Candida albicans; two, C. tropicalis; four, other nonalbicans Candida). The duration of candiduria prior to entry ranged from 18 to 180 days. Predisposing conditions included renal transplantation (1), diabetes mellitus (8), genitourinary stones (1) or anomalies (4), catheterization (2), and antibacterial therapy (11). A single patient was intolerant of AmB. Out of 11 evaluable candiduric episodes, eight resolved. Failure occurred in one patient with a chronic indwelling bladder catheter and in the allograft recipient. The data suggest that the sustained urinary excretion of AmB may permit successful single- or paucidose therapy of Candida urinary tract infections in some patients with a minimum of toxicity.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Female; Humans; Injections, Intravenous; Male; Middle Aged; Urinary Tract Infections

The aim of this study was to evaluate the efficacy of two antifungal prophylaxis regimens in liver transplant recipients. One hundred and twenty-nine consecutive recipients were randomized to receive sequential treatment with intravenous liposomal amphotericin B + oral itraconazole, intravenous fluconazole + oral itraconazole, or intravenous and oral placebo. Frequency and incidence of mycotic colonization, local and systemic infection of mycotic origin, causes of death, and possible risk factors for mycotic infection were evaluated. The incidence of mycotic colonization was higher in the placebo group ( P<0.01), but there was no significant difference in the incidence of infection between the three groups. Pre-transplant colonization, severity of liver disease, and graft rejection were all risk factors for the development of fungal infection. The routine use of antifungal prophylaxis for all liver transplant recipients does not seem to be justified.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluconazole; Humans; Immunosuppressive Agents; Itraconazole; Liver Diseases; Liver Transplantation; Male; Middle Aged; Mycoses; Placebos; Postoperative Complications; Survival Analysis

Over the past decade, invasive fungal infections have become an increasingly important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. To resolve this issue, we performed a prospective randomized study to compare the efficacy of fluconazole (FL) versus low-dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT. Patients undergoing allogenic or autologous HSCT were randomized to receive fluconazole 200 mg/day PO or amphotericin B 0.2 mg/kg/day IV beginning 1 day prior to commencement of conditioning regimen and continuing until engraftment, drug-associated toxicity was suspected, or systemic fungal infection was suspected or proven. High-dose amphotericin B (0.5-1.0 mg/kg/day) was started for patients with suspected or proven fungal infections. From January 1993 to December 1998, a total of 186 patients were enrolled into the trial, with 100 receiving FL and 86 receiving AmB. Eighty (43%) patients were removed from prophylaxis for persistent fever despite broad-spectrum antibacterial therapy or suspected fungal infections (FL 46 vs. AmB 34, P > 0.05). The incidence of proven fungal infections (FL 12% vs. AmB 12.8%), suspected fungal infections (FL 4% vs. AmB 2.3%), superficial fungal infections (FL 1% vs. AmB 4.6%) did not show any significant difference. The survival at 100 days post transplant was similar between the 2 groups (FL 78% vs. AmB 70%, P = 0.254). Death attributable to fungal infections was similar in both groups (6% vs. 7%, P > 0.05). We conclude that fluconazole is as effective as low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Child; Child, Preschool; Female; Fluconazole; Humans; Infant; Male; Middle Aged; Mycoses; Postoperative Complications; Stem Cell Transplantation; Time Factors; Transplantation, Autologous; Transplantation, Homologous

Caspofungin is an echinocandin agent with fungicidal activity against candida species. We performed a double-blind trial to compare caspofungin with amphotericin B deoxycholate for the primary treatment of invasive candidiasis.. We enrolled patients who had clinical evidence of infection and a positive culture for candida species from blood or another site. Patients were stratified according to the severity of disease, as indicated by the Acute Physiology and Chronic Health Evaluation (APACHE II) score, and the presence or absence of neutropenia and were randomly assigned to receive either caspofungin or amphotericin B. The study was designed to compare the efficacy of caspofungin with that of amphotericin B in patients with invasive candidiasis and in a subgroup with candidemia.. Of the 239 patients enrolled, 224 were included in the modified intention-to-treat analysis. Base-line characteristics, including the percentage of patients with neutropenia and the mean APACHE II score, were similar in the two treatment groups. A modified intention-to-treat analysis showed that the efficacy of caspofungin was similar to that of amphotericin B, with successful outcomes in 73.4 percent of the patients treated with caspofungin and in 61.7 percent of those treated with amphotericin B (difference after adjustment for APACHE II score and neutropenic status, 12.7 percentage points; 95.6 percent confidence interval, -0.7 to 26.0). An analysis of patients who met prespecified criteria for evaluation showed that caspofungin was superior, with a favorable response in 80.7 percent of patients, as compared with 64.9 percent of those who received amphotericin B (difference, 15.4 percentage points; 95.6 percent confidence interval, 1.1 to 29.7). Caspofungin was as effective as amphotericin B in patients who had candidemia, with a favorable response in 71.7 percent and 62.8 percent of patients, respectively (difference, 10.0 percentage points; 95.0 percent confidence interval, -4.5 to 24.5). There were significantly fewer drug-related adverse events in the caspofungin group than in the amphotericin B group.. Caspofungin is at least as effective as amphotericin B for the treatment of invasive candidiasis and, more specifically, candidemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; APACHE; Candida; Candidiasis; Caspofungin; Echinocandins; Female; Fungemia; Humans; Infusions, Intravenous; Lipopeptides; Male; Middle Aged; Neutropenia; Peptides; Peptides, Cyclic; Recurrence

Caspofungin is an antifungal agent of the novel echinocandin class. We investigated its efficacy, safety, and tolerability as therapy for oropharyngeal and/or esophageal candidiasis in a phase II dose-ranging study. Patients were randomized in a double-blind manner to receive either caspofungin acetate (35, 50, or 70 mg) or amphotericin B (0.5 mg/kg of body weight) intravenously once daily for 7 to 14 days. A favorable response required both complete resolution of symptoms and quantifiable improvement of mucosal lesions 3 to 4 days after discontinuation of study drug. Efficacy was assessed using a modified intent-to-treat analysis. No hypothesis testing of efficacy was planned or performed. Of 140 enrolled patients, 63% had esophageal involvement and 98% were infected with the human immunodeficiency virus (HIV) (median CD4 count, 30/mm(3)). A modestly higher proportion of patients in each of the caspofungin groups (74 to 91%) achieved favorable responses compared to amphotericin B recipients (63%), but there was considerable overlap in the 95% confidence intervals surrounding these point estimates. Similar trends were found in the subgroups with esophageal involvement, a history of fluconazole failure, and CD4 counts of < or =50/mm(3). A smaller proportion of patients receiving any dose of caspofungin experienced drug-related adverse events compared to patients given standard doses of conventional amphotericin B (P < 0.01). Caspofungin provided a generally well-tolerated parenteral therapeutic option for HIV-infected patients with oropharyngeal and/or esophageal candidiasis in this study.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Caspofungin; Double-Blind Method; Drug Tolerance; Echinocandins; Esophageal Diseases; Female; Humans; Lipopeptides; Male; Middle Aged; Peptides; Peptides, Cyclic; Pharyngeal Diseases; Treatment Outcome

To determine the usage patterns of the lipid-based amphotericin B formulations at our institution and to compare the observed nephrotoxicity and efficacy of these formulations.. Prospective and retrospective observational study. Urban 350-bed teaching hospital.. Sixty-seven nonhemodialysis patients who were prescribed greater than 3 days of amphotericin B lipid complex (ABLC) or liposomal amphotericin B (L-AmB) from 1996-1999.. Forty-six patients received ABLC and 21 received L-AmB. Oncology patients accounted for most prescriptions of both formulations. Amphotericin B lipid complex most frequently was prescribed for treatment of documented fungal infections (50%), followed by treatment of neutropenic fever (33%). Liposomal amphotericin B most frequently was prescribed for treatment of neutropenic fever (62%), followed by treatment of documented fungal infections (29%). Seventy-eight percent of patients treated with ABLC and 90% of those who received L-AmB were started on the lipid-based formulation due to being refractory or intolerant to prior antifungal therapy. Two (4.4%) patients receiving ABLC and four (19%) patients receiving L-AmB experienced nephrotoxicity at the end of therapy (NS). Of the patients with a documented fungal infection, 20 out of 23 (87%) of those treated with ABLC and 4 out of 5 (80%) of those treated with L-AmB had a complete or partial response to therapy (NS). One patient with febrile neutropenia had a breakthrough fungal infection while receiving L-AmB.. No significant differences in nephrotoxicity or efficacy were found between ABLC and L-AmB. Until further studies indicate clinically significant differences in nephrotoxicity between the two liposomal amphotericin B formulations, it is recommended that economics continue to be the major determinant for product selection.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Drug Carriers; Female; Humans; Kidney Diseases; Lipids; Liposomes; Male; Middle Aged; Neutropenia; Prospective Studies; Retrospective Studies

Caspofungin is a new broad-spectrum antifungal drug. A multicenter, double-blind, randomized trial was conducted to assess the efficacy, safety, and tolerability of caspofungin relative to amphotericin B in adults with endoscopically documented symptomatic Candida esophagitis. By use of a modified intent-to-treat analysis, endoscopically verified clinical success was achieved in 74% (95% confidence interval [CI], 59%-86%) and 89% (95% CI, 72%-98%) of patients receiving caspofungin at 50 and 70 mg/day, respectively, and in 63% (95% CI, 49%-76%) of patients given amphotericin B at 0.5 mg/kg/day. Therapy was stopped because of drug-related adverse events in 24% of patients in the amphotericin B group and 4% and 7%, respectively, for the caspofungin groups. This report provides the first demonstration of clinical utility for an echinocandin compound. Caspofungin appeared in this study to be as effective as and better tolerated than amphotericin B for the treatment of esophageal candidiasis.

Topics: Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Caspofungin; Consumer Product Safety; Double-Blind Method; Drug Tolerance; Echinocandins; Esophagitis; Esophagoscopy; Female; Humans; Lipopeptides; Male; Middle Aged; Peptides; Peptides, Cyclic

To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients, we conducted a prospective, double-blind, placebo-controlled, randomized trial. Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole (100 mg orally twice daily; n=104) or of placebo (n=106). Overall, fungal infections (superficial or systemic) occurred more frequently in the placebo group (15% vs. 6%; P=.03). There were no differences in the empirical use of amphotericin B or systemic fungal infections. Among patients with neutropenia that was profound (<100 neutrophils/mm3) and prolonged (for at least 7 days), those receiving itraconazole used less empirical amphotericin B (22% vs. 61%; P=.0001) and developed fewer systemic fungal infections (6% vs. 19%; P=.04). For patients with profound and prolonged neutropenia, itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin B.

Topics: Administration, Oral; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Fungemia; Hematologic Neoplasms; Humans; Itraconazole; Male; Middle Aged; Neutropenia; Prospective Studies; Survival Rate; Transplantation, Autologous; Treatment Outcome

Amphotericin B is efficacious for the treatment of systemic candidiasis, however it has potentially serious toxic effects. Administration as lipid emulsions has been advocated to decrease its toxicity.. To compare the safety and tolerance of amphotericin B administered as lipid emulsion or dissolved in dextrose in water.. Forty five patients with confirmed or highly suspected systemic candidiasis were studied. Between January 1996 and June 1997 amphotericin B was administered in dextrose in water to 17 patients (group 1). Between July 1997 and December 1998, the drug was delivered in lipid emulsions (Intralipid, group 2). Clinical and laboratory parameters (serum creatinine, urea nitrogen and potassium), were assessed daily.. Both treatment groups were clinically comparable and had the same survival. Accumulative amphotericin B dose administered was 343.2 +/- 197 and 414.6 +/- 518 mg respectively. Hypokalemia was more frequent in group 2 (52 and 25% respectively, p < 0.05). There were no differences in the outcome of renal function or other adverse reactions.. Administration of amphotericin B as lipid emulsions did not reduce its toxicity in critical patients (Rev Méd Chile 2000; 128: 1101-07).

Topics: Amphotericin B; Antifungal Agents; APACHE; Candidiasis; Chi-Square Distribution; Fat Emulsions, Intravenous; Female; Glucose; Humans; Intensive Care Units; Male; Middle Aged

Ninety-nine Candida bloodstream isolates underwent testing for susceptibility to amphotericin B by the E test, and the results were correlated with patients' responses to amphotericin B. The MICs for isolates that were associated with therapeutic failure were significantly higher than the MICs for those associated with therapeutic success. A MIC of >/=0.38 microgram/ml identified isolates likely to be associated with therapeutic failure.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Humans; Microbial Sensitivity Tests; Prospective Studies

Lipid formulations of amphotericin B have been recently introduced for treatment of invasive fungal infections. However, little is known about their role in pediatric populations.. We studied the safety and antifungal efficacy of amphotericin B lipid complex (ABLC, Abelcet) in 111 treatment episodes in pediatric patients through an open label, emergency use multicenter study. Patients with invasive fungal infections were enrolled if they had mycoses refractory to conventional antifungal therapy, if they were intolerant of previous systemic antifungal agents or concomitant nephrotoxic drugs or if they had preexisting renal disease.. All 111 treatment episodes were evaluable for safety and 54 were evaluable for efficacy. The mean serum creatinine for the study population did not significantly change between baseline (1.23 +/- 0.11 mg/dl) and cessation of ABLC therapy (1.32 +/- 0.12 mg/dl) during 6 weeks. There were no significant differences observed between initial and end-of-therapy levels of serum potassium, magnesium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and hemoglobin. However, there was an increase in mean total bilirubin (3.66 +/- 0.73 to 5.31 +/- 1.09 mg/dl) at the end of therapy (P = 0.054). Among 54 cases fulfilling criteria for evaluation of antifungal efficacy, a complete or partial therapeutic response was obtained in 38 patients (70%) after ABLC therapy. Complete or partial therapeutic response was documented in 56% of cases with aspergillosis (n = 25) and in 81% (n = 27) with candidiasis. Among premature infants (n = 8) and allogeneic marrow recipients (n = 14), response rates were 88 and 57%, respectively. Response was similar in those patients enrolled because of intolerance to previous antifungal therapy or because of progressive infection.. These data support the use of ABLC for treatment of invasive fungal infections in pediatric patients who are intolerant of or refractory to conventional antifungal therapy.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Child; Child, Preschool; Creatinine; Drug Combinations; Female; Humans; Infant; Infant, Newborn; Male; Mycoses; Phosphatidylcholines; Phosphatidylglycerols; Zygomycosis

We evaluated an amphotericin treatment strategy on the basis of duration of candidemia and clinical findings. Patients without neutropenia who had uncomplicated candidemia received 200 mg of amphotericin B over 5-7 days if they had had 1 day of positive cultures (PC group). The clinical cure rate was 93% (95% confidence interval [CI], 77%-99%; n=29 episodes) in the SC group, with no relapses (median follow-up, 272 days). The clinical cure rate was 83% (95% CI, 64%-94%; n=29 episodes) in the PC group, with 1 relapse (4.2%). The results of this pilot study suggest that patients with candidemia may be stratified into risk groups on the basis of the duration of positive blood cultures and other clinical findings. Decisions about the duration of therapy can be made 4-7 days after initiation of treatment. Carefully selected patients with transient uncomplicated candidemia may be safely treated with a short course of amphotericin B. Further prospective validation of this concept should be undertaken particularly to evaluate the impact on low-frequency late complications (e.g., endophthalmitis).

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Chest Pain; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Pilot Projects; Recurrence; Survival Rate; Time Factors; Treatment Outcome

A study was conducted to compare the renal effects of amphotericin B lipid complex (ABLC), a lipid formulation of the widely used antifungal medication, with conventional amphotericin B (AmB) in the treatment of serious fungal infections, including invasive candidiasis, cryptococcal meningitis, and aspergillosis. The clinical experience of ABLC includes two types of open-label studies: randomized comparative (ABLC 5 mg/kg/d compared with AmB 0.6 to 1 mg/kg) and emergency use. In the comparative studies, changes in serum creatinine were evaluated three ways: doubling of the baseline value, an increase from < or = 1.5 mg/dL at baseline to > or = 1.5 mg/dL, and an increase from < or = 1.5 mg/dL at baseline to > or = 2.0 mg/dL. More patients in the AmB group reached these end points than in the ABLC group (P < or = 0.007), and the time needed to reach each of these end points was significantly shorter for the AmB group (P < or = 0.02). Increased serum creatinine was reported as an adverse event more frequently by patients receiving AmB than by patients receiving ABLC. In the emergency use study, a steady and statistically significant decrease in serum creatinine was observed among patients who started ABLC treatment with serum creatinine greater than 2.5 mg/dL due to prior AmB treatment. ABLC offers the physician a valuable, less-nephrotoxic alternative to AmB for the treatment of patients with severe, invasive fungal infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Creatinine; Drug Combinations; Female; Humans; Kidney; Male; Meningitis, Cryptococcal; Middle Aged; Mycoses; Phosphatidylcholines; Phosphatidylglycerols

The safety and antifungal efficacy of amphotericin B lipid complex (ABLC) were evaluated in 556 cases of invasive fungal infection treated through an open-label, single-patient, emergency-use study of patients who were refractory to or intolerant of conventional antifungal therapy. All 556 treatment episodes were evaluable for safety. During the course of ABLC therapy, serum creatinine levels significantly decreased from baseline (P < .02). Among 162 patients with serum creatinine values > or = 2.5 mg/dL at the start of ABLC therapy (baseline), the mean serum creatinine value decreased significantly from the first week through the sixth week (P < or = .0003). Among the 291 mycologically confirmed cases evaluable for therapeutic response, there was a complete or partial response to ABLC in 167 (57%), including 42% (55) of 130 cases of aspergillosis, 67% (28) of 42 cases of disseminated candidiasis, 71% (17) of 24 cases of zygomycosis, and 82% (9) of 11 cases of fusariosis. Response rates varied according to the pattern of invasive fungal infection, underlying condition, and reason for enrollment (intolerance versus progressive infection). These findings support the use of ABLC in the treatment of invasive fungal infections in patients who are intolerant of or refractory to conventional antifungal therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Creatinine; Cryptococcosis; Drug Combinations; Female; Humans; Male; Mycoses; Phosphatidylcholines; Phosphatidylglycerols

Fluconazole (FLU) is an alternative to amphotericin B (AMB) for the treatment of candidemia in non-neutropenic patients. This agent has similar clinical efficacy but significantly reduced adverse effects compared with AMB. Using the database from a Canadian randomised multicentre comparative trial of FLU versus AMB in the treatment of non-neutropenic patients with candidemia, an economic analysis of antifungal therapy was conducted from a Canadian hospital perspective. Patient records were examined for information containing hospital resource consumption. This included the costs for primary intravenous therapy with either AMB or FLU, laboratory tests, patient clinical monitoring and adverse effects management. The robustness of the baseline results were then tested by a comprehensive sensitivity analysis. The mean duration of therapy in the AMB and FLU arms was 17.1 and 23.7 days, respectively (p < 0.001). Assuming that all of the FLU was administered intravenously, the outcomes of the baseline economic analysis revealed that the treatment cost for patients randomized to receive FLU was approximately 50% higher than that for patients treated with AMB [AMB: $Can2370 vs FLU: $Can3578; p = 0.001 ($Can = Canadian dollars)]. In the sensitivity analysis, substitution to oral FLU after 7 days of intravenous therapy produced economic differences that were no longer statistically significant (AMB: $Can2370 vs FLU: $Can2705; p = 0.10). These results suggest that the FLU administration regimen used in the Canadian randomized trial for the treatment of candidemia in non-neutropenic patients may result in increased hospital costs compared with AMB. However, comparable expenditures could be realized if FLU is administered intravenously for the first 7 days and then orally in patients whose condition allows for reliable oral therapy.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Female; Fluconazole; Fungemia; Health Care Costs; Humans; Male; Middle Aged

To determine the incidence and prognosis of candidemia in non-neutropenic critically ill patients, to define mortality-related factors, and to evaluate the results of systemic antifungal therapy.. A prospective multicenter survey in which medical and/or surgical intensive care units (ICUs) in 28 hospitals in Spain participated.. All critically ill patients with positive blood cultures for Candida species admitted to the participating ICUs over a 15-month period were included.. Candidemia was defined as the presence of at least one positive blood culture containing Candida species. The follow-up period was defined as the time elapsed from the first positive blood culture for Candida species to discharge or death during hospitalization. Antifungal therapy was considered to be "early" when it was administered within 48 h of the date when the first positive blood culture was obtained and "late" when it was administered more than 48 h after the first positive blood culture.. Candidemia was diagnosed in 46 patients (mean age 59 years), with an incidence of 1 critically ill patient per 500 ICU admissions. The species most frequently isolated were Candida albicans (60%) and C. parapsilosis (17%). Fluconazole alone was given to 27 patients, amphotericin B alone to 10, and sequential therapy to 6. Three patients did not receive antifungal therapy. The overall mortality was 56% and the attributable mortality 21.7%. In the univariate analysis, mortality was significantly associated with a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score at the onset of candidemia (p = 0.04) and with the time elapsed between the episode of candidemia and the start of antifungal therapy 48 h or more later (p < 0.02). Patients with an APACHE II score lower than 21 at the onset of candidemia had a higher probability of survival than patients who were more seriously ill (p = 0.04). Patients with "early" antifungal therapy (< or = 48 h between the onset of candidemia and the start of antifungal therapy) had a higher probability of survival compared with patients with late therapy (p = 0.06). No significant differences were noted between the two groups on different antifungal therapy.. The incidence of candidemia in ICU patients was very low. An APACHE II score > 20 at the time of candidemia was associated with a higher mortality. Further studies with a large number of patients are needed to assess the effect of early antifungal therapy on the decrease in mortality associated with candidemia and to determine the appropriate dosage of fluconazole and duration of treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; APACHE; Candidiasis; Critical Illness; Cross Infection; Data Interpretation, Statistical; Female; Fluconazole; Fungemia; Humans; Incidence; Intensive Care Units; Male; Middle Aged; Prognosis; Prospective Studies; Spain

A randomized trial was conducted to compare the efficacy and safety of fluconazole versus that of amphotericin B in the treatment of candidemia in non-neutropenic adults. Enrollment was stratified by disease severity (APACHE II score). Patients were randomized (1:1) to receive amphotericin B 0.6 mg/kg/day (cumulative dose 8 mg/kg) or fluconazole 800 mg intravenous loading dose, then 400 mg daily for four weeks (intravenous for at least 10 days). Patients were monitored for six months. A total of 106 patients were enrolled. A protocol amendment implemented midway through the trial required patients to be removed from the study and treated with amphotericin B if species identification indicated candidemia due to Candida glabrata or Candida krusei. Baseline characteristics were similar for the two groups; 103 patients (fluconazole, 50; amphotericin B, 53) met the major enrollment criteria. The intention-to-treat analysis indicated successful therapy in 50% of fluconazole recipients compared to 58% of the amphotericin B group (p = 0.39; one-sided 95% CI, -8 to 24%). The efficacy analysis included 84 patients (fluconazole, 42; amphotericin B, 42); successful outcomes were observed in 57% and 62% of cases in the fluconazole and amphotericin B groups, respectively (p = 0.66: one-sided 95% CI, -12 to 22%). The mortality at day 14 for the fluconazole group was 26% and for the amphotericin B group 21% (p = 0.52; chi-square test) and remained similar throughout the course of follow-up, Drug-related adverse events were more frequent with amphotericin B than with fluconazole and prompted switching of therapy for two (4%) and zero cases, respectively. Fluconazole and amphotericin B were associated with similar clinical response rates and survival in the treatment of candidemia among non-neutropenic patients; however, drug-related adverse events were more frequent with amphotericin B.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Confidence Intervals; Female; Fluconazole; Fungemia; Humans; Immunocompetence; Male; Middle Aged; Survival Rate; Treatment Outcome

The safety, tolerance, and pharmacokinetics of amphotericin B lipid complex (ABLC) were studied in a cohort of pediatric cancer patients. Six children with hepatosplenic candidiasis (HSC) received 2.5 mg of ABLC/kg of body weight/day for 6 weeks for a total dosage of 105 mg/kg. Mean serum creatinine (0.85 +/- 0.12 mg/dl at baseline) was stable at the end of therapy at 0.85 +/- 0.18 mg/dl and at 1-month follow-up at 0.72 +/- 0.12 mg/dl. There was no increase in hepatic transaminases. Mean plasma concentrations over the dosing interval (C(ave)) and area under the curve from 0 to 24 h (AUC(0-24h)) increased between the first and seventh doses but were similar between doses 7 and 42, suggesting that steady state was achieved by day 7 of therapy. Following the final (42nd) dose of ABLC, mean AUC(0-24h) was 11.9 +/- 2.6 microg h/ml, C(ave) was 0.50 +/- 0.11 microg/ml, maximum concentration of the drug in whole blood was 1.69 +/- 0.75 microg/ml, and clearance was 3.64 +/- 0.78 ml/min/kg. Response of hepatic and splenic lesions was monitored by serial computerized tomographic and magnetic resonance imaging scans. The five evaluable patients responded to ABLC with complete or partial resolution of physical findings and of lesions of HSC. During the course of ABLC infusions and follow-up, there was no progression of HSC, breakthrough fungemia, or posttherapy recurrence. Hepatic lesions continued to resolve after the completion of administration of ABLC. Thus, ABLC administered in multiple doses to children was safe, was characterized by a steady state attainable within 1 week of therapy, and was effective in treatment of HSC.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Drug Combinations; Female; Humans; Liver Diseases; Male; Phosphatidylcholines; Phosphatidylglycerols; Splenic Diseases

Systemic candidiasis with renal involvement is a rare but well-recognized complication during neonatal intensive care treatment. In addition to intravenous administration of amphotericin B, decompression of the renal pelvis and irrigation of the involved kidney with the same drug through a nephrostomy tube will provide a high concentration of antifungal agent with a flushing effect. This procedure is not always possible due to the small size of the neonatal kidneys. We have conceived a new percutaneous trocar nephrostomy which allows its application directly in an incubator without using X-rays during a single procedure. In 3 cases a bilateral percutaneous nephrostomy was performed directly in the incubator using a one-step ultrasonically guided maneuver under local anesthesia. The funguria was successfully eradicated in all cases. The availability of a nephrostomy trocar of small dimensions leads us to an improved renal approach in newborns.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Combined Modality Therapy; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Kidney Diseases; Nephrostomy, Percutaneous; Therapeutic Irrigation; Ultrasonics

Amphotericin B colloidal dispersion (ABCD; Amphocil) was evaluated in a phase I dose-escalation study in 75 marrow transplant patients with invasive fungal infections (primarily Aspergillus or Candida species) to determine the toxicity profile, maximum tolerated dose, and clinical response. Escalating doses of 0.5-8.0 mg/kg in 0.5-mg/kg/patient increments were given up to 6 weeks. No infusion-related toxicities were observed in 32% of the patients; 52% had grade 2 and 5% had grade 3 toxicity. No appreciable renal toxicity was observed at any dose level. The estimated maximum tolerated dose was 7.5 mg/kg, defined by rigors and chills and hypotension in 3 of 5 patients at 8.0 mg/kg. The complete or partial response rate across dose levels and infection types was 52%. For specific types of infections, 53% of patients with fungemia had complete responses, and 52% of patients with pneumonia had complete or partial responses. ABCD was safe at doses to 7.5 mg/kg and had tolerable-infusion-related toxicity and demonstrable antifungal activity.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspartate Aminotransferases; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Chemical and Drug Induced Liver Injury; Cholesterol Esters; Creatinine; Humans; Kidney Diseases; Mycoses

To evaluate the differences in efficacy and in clinical and biochemical tolerance to amphotericin B administered in a lipid emulsion compared with amphotericin B administered in 5% dextrose in water in the treatment of Candida albicans infection in intensive care unit (ICU) patients.. Prospective, controlled, randomized study, conducted during a 2.5-yr period, comparing the two treatment protocols.. General ICU of a university-affiliated municipal hospital.. Sixty consecutive critically ill patients with confirmed or suspected Candida infection.. Patients received amphotericin B (1 mg/kg/24 hrs), administered randomly in 5% dextrose in water (group A), or in lipid emulsion (20% intralipid) (group B).. Clinical tolerance (fever, chills, hemodynamics), hepatorenal tolerance, and biological tolerance (serum electrolytes and coagulation profile) were evaluated. Patients receiving amphotericin B in lipid emulsion experienced a lower frequency rate of drug-associated fever (61.4% vs. 5.8%, p < .003) rigors (54% vs. 8.5%, p < .004), hypotension (17% vs. 0%), and nephrotoxicity (increase of serum creatinine concentration 66.7% vs. 20%, p < .0002). Significant (264,500 +/- 71,460 to 163,570 +/- 34,450 mm3, p < .01) thrombocytopenia, not associated with active bleeding, occurred in patients receiving amphotericin B lipid in emulsion but not in patients receiving the drug in dextrose.. Treatment with amphotericin B in a lipid emulsion when given to critically ill patients with Candida sepsis seems to be safer and as effective as the conventional mode of administration.

Topics: Adult; Aged; Amphotericin B; Candidiasis; Critical Illness; Fat Emulsions, Intravenous; Female; Glucose; Humans; Infusions, Intravenous; Intensive Care Units; Liver Function Tests; Male; Middle Aged; Prospective Studies; Renal Insufficiency; Solutions

To compare the efficacy and toxicity of fluconazole and amphotericin B in the treatment of hematogenous candidiasis in cancer patients.. A matched cohort study of cancer patients with hematogenous candidiasis was conducted. Forty-five patients with hematogenous candidiasis who received fluconazole (200 to 600 mg/day) in an open-label trial at the University of Texas M. D. Anderson Cancer Center, Houston, Texas, between February 1990 and June 1992 were matched to 45 patients treated with amphotericin B (0.3 to 1.2 mg/kg/day) for the same diagnosis. Criteria for matching included the following prognostic variables at the initiation of therapy: pneumonia, neutropenia (< 1,000 cells/mm3), number of positive blood cultures before therapy, infecting Candida species, underlying disease, and the simplified acute physiology score. Response and survival at 48 hours, after 5 days of therapy, and at the end of therapy, as well as toxicity rates were obtained. Other post hoc analyses were performed. Differences in outcomes were assessed by the McNemar, the sign, and the log rank tests.. Patients were similar with respect to the matching criteria, age, sex, status of underlying disease, use of antibiotics and growth factors, duration of treatment, presence and removal of central venous catheters, disseminated disease, and concomitant infections. Response rates at 48 hours and 5 days were similar between the two study groups. Overall response rates at the end of therapy were 73% for patients treated with fluconazole and 71% for patients treated with amphotericin B (P = 0.78). There were no differences in survival rates or causes of death. Toxicity was observed in 9% of patients treated with fluconazole and in 67% of patients treated with amphotericin B (P < 0.0001). Toxic effects of amphotericin B included nephrotoxicity, hypokaliemia, and fever and chills.. Fluconazole is effective and better tolerated than amphotericin B for the treatment of hematogenous candidiasis in cancer patients.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Case-Control Studies; Female; Fluconazole; Fungemia; Humans; Male; Middle Aged; Treatment Outcome

Fungal urinary tract infections are increasingly prevalent in the elderly in acute and chronic care settings. This randomized trial compares the efficacy and safety of oral fluconazole with the efficacy and safety of bladder irrigation with amphotericin B for treatment of funguria (> or = 10,000 cfu/mL of urine) in 109 hospitalized elderly patients. A second treatment course was given for persistent funguria. Indwelling bladder catheters were present in 69% of the patients. While Candida albicans was the predominant isolate from catheterized patients, C. albicans, Candida tropicalis, and Torulopsis glabrata were recovered from noncatheterized patients. Two days after completion of treatment, funguria was eradicated in 96% of the patients treated with amphotericin B and 73% of those treated with fluconazole (P < .05). At 1 month after study enrollment, the mortality rate associated with all causes was greater among patients who were treated with amphotericin B bladder irrigation than among those who received oral fluconazole therapy (41% vs. 22%, respectively; P < .05); this finding suggests that local therapy may be associated with poorer survival. The proportion of patients without funguria at 1 month after study enrollment was similar in the two treatment groups (84%, amphotericin B group; 80%, fluconazole group). A few minor and mild adverse events occurred.

Topics: Administration, Oral; Aged; Aged, 80 and over; Amphotericin B; Candidiasis; Combined Modality Therapy; Female; Fluconazole; Follow-Up Studies; Humans; Male; Therapeutic Irrigation; Treatment Outcome; Urinary Bladder; Urinary Tract Infections

We conducted a prospective, randomized, multicenter study comparing fluconazole and amphotericin B in the treatment of candidal infections. One hundred and sixty-four patients (60 of whom were neutropenic) with documented or presumed invasive candidiasis were assigned to treatment with either fluconazole (400 mg daily) or amphotericin B (25-50 mg daily; 0.67 mg/kg daily for neutropenic patients). Clinical response and survival rates were assessed at 48 hours, after 5 days, and at the end of therapy. Overall response rates to fluconazole and amphotericin B were similar (66% and 64%, respectively). There were no differences in response as related to site of infection, pathogen, time to defervescence, relapse, or survival rates between the groups. Adverse effects were more frequent with amphotericin B (35%) than with fluconazole (5%; P < .0001). The results of this study confirm that fluconazole is as effective as but better tolerated than amphotericin B in the treatment of candidal infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Candidiasis; Female; Fluconazole; Humans; Male; Prospective Studies; Treatment Failure; Treatment Outcome

The antifungal susceptibilities of 232 pathogenic blood stream Candida isolates collected during a recently completed trial comparing fluconazole (400 mg/day) with amphotericin B (0.5 mg/kg of body weight per day) as treatment for candidemia in the nonneutropenic patient were determined both by the National committee for Clinical Laboratory Standards M27-P macrobroth methodology and by a less cumbersome broth microdilution methodology. For amphotericin B, M27-P yielded a very narrow range of MICs (0.125 to 1 microgram/ml) and there were no susceptibility differences among species. For fluconazole, a broad range of MICs were seen (0.125 to > 64 micrograms/ml), with characteristic MICs seen for each species in the rank order Candida albicans < C. parapsilosis approximately equal to C. lusitaniae < C. glabrata approximately equal to C. krusei approximately equal to C. lipolytica. The MIC distribution for C. tropicalis was bimodal and could not be ranked. Both microdilution MICs were within one tube dilution of the M27-P MIC for > 90% of isolates with amphotericin B and for > or = 77% of isolates with fluconazole. For both methods, elevated MICs did not predict treatment failure. In the case of amphotericin B, the MIC range was too narrow to permit identification of resistant isolates. In the case of fluconazole, MICs for isolates associated with failure to clear the bloodstream consistently were equivalent to the median MIC for the given species. Successful courses of therapy were seen with four isolates from four patients despite MICs of > or = 32 micrograms/ml. As MICs obtained by M27-P and similar methods correlate with responsiveness to fluconazole therapy in animal models and in AIDS patients with oropharyngeal candidiasis, the lack of correlation in this setting suggests that the MICs for these isolates are at or below the relevant fluconazole breakpoint for this dose of fluconazole and patient setting and that host factors such as failure to exchange intravenous catheters were more important than MIC in predicting outcome.

Topics: Amphotericin B; Candida; Candidiasis; Fluconazole; Fungemia; Humans; Microbial Sensitivity Tests

A randomized, double-blind, placebo-controlled trial assessed the efficacy and toxicity of 400 mg/day fluconazole in preventing fungal infections during the first 75 days after marrow transplantation. During prophylaxis, systemic fungal infections occurred in 10 (7%) of 152 fluconazole-treated patients compared with 26 (18%) of 148 placebo-treated patients (P = .004). There were no Candida albicans infections in fluconazole recipients compared with 18 in placebo recipients (P < .001) and no significant increase in Candida infections other than C. albicans. Fluconazole also significantly reduced the incidence of superficial fungal infections (P < .001), fungal colonization (P = .037), and empiric amphotericin B use (P = .005). The probability of survival was improved in fluconazole recipients, in whom 31 deaths occurred up to day 110 after transplantation compared with 52 deaths in placebo recipients (P = .004). No clinically significant toxicity was detected with fluconazole use. Prophylactic fluconazole was safe and significantly reduced systemic fungal infections with other benefits, including improved survival at day 110 after marrow transplantation.

Topics: Adolescent; Adult; Amphotericin B; Bone Marrow Transplantation; Candida; Candidiasis; Double-Blind Method; Drug Resistance, Microbial; Female; Fluconazole; Humans; Male; Middle Aged; Opportunistic Infections; Patient Compliance; Prospective Studies; Survival Analysis

Eighty-six consecutive liver transplant recipients were prospectively randomized in a double-blind, placebo-controlled antifungal prophylaxis study. Seventy-seven patients received 5 days of prophylaxis starting during the transplantation with either liposomal amphotericin B (AmBisome) 1 mg/kg/day or placebo. Among 40 AmBisome-treated patients, no invasive Candida infection was seen during the first month, compared with 5 invasive Candida albicans infections among 37 control patients (P < 0.05). Furthermore, 1 placebo patient experienced Aspergillus niger pneumonia. Thus, the overall incidence of invasive fungal infections was 0/40 (0%) in the AmBisome group versus 6/37 (16%) in the placebo group (P < 0.01). Patient survival at 30 days was 92% versus 94% for AmBisome- and placebo-treated patients, respectively. One patient experienced backache related to AmBisome infusion. Two patients had transient thrombocytopenia possibly caused by AmBisome treatment. AmBisome was otherwise well tolerated. The total cost for all antifungal drugs used in both groups was equal. However, prophylaxis with AmBisome was $5000 less expensive than treatment of proven invasive fungal infections among placebo patients.

Topics: Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Aspergillus niger; Candidiasis; Costs and Cost Analysis; Double-Blind Method; Drug Carriers; Female; Humans; Immunosuppressive Agents; Kidney Function Tests; Liposomes; Liver Function Tests; Liver Transplantation; Lung Diseases, Fungal; Male; Middle Aged; Opportunistic Infections

Topics: Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Candidiasis; Child; Child, Preschool; Drug Carriers; Female; Follow-Up Studies; Humans; Infant; Liposomes; Liver Transplantation; Male; Middle Aged; Mycoses; Placebos; Postoperative Complications; Probability; Risk Factors; Time Factors; Tissue Donors

A randomized trial was conducted to compare amphotericin B bladder irrigation (AmBBI) with oral fluconazole in terms of efficacy and safety in the treatment of candidal funguria. Fifty-three patients with two consecutive positive funal cultures of urine were randomized to undergo AmBBI (50 mg/L over 24 hours or 50 mg/L for 7 days) or to receive fluconazole (200 mg/d for 7 days). Urinary catheters were changed upon entry into the study and following therapy. Blood and urine specimens were obtained throughout the study. Candida albicans was the species isolated most frequently from urine cultures. Eradication rates for funguria at 24 hours and 5-9 days after therapy were 82.4% and 75%, respectively, with the 7-day AmBBI regimen; and 83.3% and 76.9%, respectively, with fluconazole. There were no differences in the posttherapy eradication rates between the regimens at 24 hours (P = .597) and at 5-9 days (P = .66). Candida glabrata was the predominant organism recovered from patients in the fluconazole group 5-9 days after the completion of therapy. Adverse events were limited to bladder fullness in a patient who underwent AmBBI and hypoglycemia in a patient who received concomitant therapy with fluconazole and glyburide. AmBBI (once or for 7 days) and fluconazole appear to be equally efficacious in the treatment of candidal funguria.

Topics: Administration, Oral; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Costs and Cost Analysis; Female; Fluconazole; Follow-Up Studies; Humans; Male; Therapeutic Irrigation; Treatment Outcome; Urinary Bladder

During a comparative trial of amphotericin B vs. fluconazole for treatment of candidemia in nonneutropenic patients, data on the management of intravascular catheters were collected. Complete records were available for 91% of the 206 study patients. For the subset of patients with a catheter in place at the time of their first positive blood culture, removal and replacement of all intravascular catheters without exchange over a guidewire from a preexisting line on or before the first day the study drug was administered were associated with a reduction in the subsequent mean duration (+/- SE) of candidemia, from 5.6 +/ -0.8 days to 2.6 +/- 0.5 days (P < .001).

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Catheterization; Fluconazole; Humans; Time Factors

Sepsis due to candida infection is a major cause of mortality and morbidity on our unit. Over a period of 3 years and 4 months, 29 cases of candida septicaemia, diagnosed by blood cultures, were encountered at the burn unit at Augusta Regional Medical Center. Factors known to predispose to fungal sepsis were present in all cases. All patients had large burns (14-98 per cent total body surface (TBSA) with a mean of 48.3 per cent). All but one patient had at least one central venous line. Respiratory problems requiring ventilator support were present in 24 patients. Sixteen patients had Candida albicans sepsis, two in association with another fungal sepsis. Candida parapsilosis was encountered in nine patients, one in combination with another species. Four patients had Candida tropicalis. Amphotericin B was prescribed therapeutically in 25 patients, in seven together with fluconazole. Two patients received fluconazole only and two received no antifungal therapy. There were eight deaths all attributed to sepsis and all of whom had multiple organ failure. Five of those who died had completed a course of amphotericin B therapy, two were receiving treatment at the time of death, and one patient died before culture data became available. Early and aggressive therapy is advised and amphotericin B appears to be the drug of choice.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Burn Units; Burns; Candidiasis; Child; Fluconazole; Fungemia; Humans; Middle Aged

The efficacy of single amphotericin B bladder washout was assessed, and the source of infection was sought, in 47 patients with 62 separate episodes of candiduria. After a single bladder washout, 44 of 62 (71%) candiduria episodes cleared and none of these patients had evidence of invasive disease or kidney infection. Ten (56%) of 18 patients with persistent candiduria had no evidence of invasive disease or kidney infection at autopsy or clinically. The sensitivity of a positive urine culture for Candida spp. after a single amphotericin B bladder washout in predicting kidney infection or invasive candidiasis was 100% (CI = 63-100%); but the specificity was only 81% (CI = 47-100%) and the positive predictive value only 44%.

Topics: Administration, Intravesical; Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Female; Humans; Male; Middle Aged; Prospective Studies; Urinary Catheterization

The aim of this study was to determine the efficacy of orally administered amphotericin B (Ampho B) on the elimination and suppression of yeasts in the orointestinal tract and on the clinical success regarding the Ampho B concentrations in faeces and serum. A total of 23 newborns at risk suffering from oral and/or cutaneous candidosis and massive colonization of yeasts in the orointestinal tract received Ampho-Moronal suspension (Squibb-Heyden, München) for 10 days: newborns < 1500 g 4 x 20 mg Ampho B/d and newborns > 1500 g 4 x 40 mg/d. Ampho B was detected in concentrations between 0.6 and 20 micrograms/g in the faeces of all patients 24 hours after beginning and 2-6 days after the end of the application. During this time Ampho B concentrations between 0.06 and 0.58 microgram/ml were also detected in the serum of the newborns. During the administration of Ampho-Moronal suspension for 10 days the initial available yeasts were eliminated in 18 patients (78%) out of the faeces. In 7 out of 17 patients (41%) the oral and cutaneous candidosis was cured. After finishing the administration of Ampho-Moronal Candida albicans was isolated again from the faeces during the following 5 days in half of the newborns who had reached negative mycological findings during the prophylaxis. For that reason Ampho-Moronal should be prophylactically administered for a longer time during the period of increased risk for systemic mycosis.

Topics: Administration, Oral; Amphotericin B; Candidiasis; Feces; Humans; Infant, Newborn; Intestinal Diseases; Mycoses; Risk Factors

The association between colonization with Candida spp., subsequent occurrence of invasive candidiasis and empiric use of amphotericin B was investigated prospectively in 139 neutropenic patients with hematologic malignancies. Treatment with amphotericin B was required in 67% of patients colonized in multiple non-contiguous body sites (multicolonized) versus 31% of patients colonized in single or contiguous sites (monocolonized) and in 21% of non-colonized patients (p = 0.0037 and p = 0.00026, respectively). Invasive candidiasis was documented in 22.2% of multicolonized versus 4.8% of monocolonized patients and in none of the non-colonized patients (p = 0.035 and p = 0.0036, respectively). Analysis of the spectrum of colonizing Candida spp. showed that multicolonized subjects were colonized with increased frequently by Candida albicans compared to monocolonized subjects, and that the association between multicolonization, invasive candidiasis and amphotericin B usage was statistically significant in patients colonized by Candida albicans but not in patients colonized by other Candida species. The association between Candida multicolonization and the occurrence of Candida infection seems to be confirmed by a double-blind placebo-controlled study performed in a small subgroup of the multicolonized patients treated with fluconazole.

Topics: Adolescent; Adult; Aged; Amphotericin B; Candida; Candidiasis; Child; Child, Preschool; Colony Count, Microbial; Double-Blind Method; Female; Fluconazole; Hematologic Diseases; Humans; Male; Middle Aged; Neutropenia; Prospective Studies

Amphotericin B has long been the standard treatment for candidemia, but its use is complicated by its toxicity. More recently, fluconazole, a water-soluble triazole with activity against candida species and little toxicity, has become available. We conducted a multicenter randomized trial that compared amphotericin B with fluconazole as treatment for candidemia.. To be eligible, patients had to have a positive blood culture for candida species, a neutrophil count > or = 500 per cubic millimeter, and no major immunodeficiency. Patients were randomly assigned to receive either amphotericin B (0.5 to 0.6 mg per kilogram of body weight per day) or fluconazole (400 mg per day), each continued for at least 14 days after the last positive blood culture. Outcomes were assessed by a group of investigators blinded to treatment assignment.. Of the 237 patients enrolled, 206 met all entry criteria. The most common diagnoses were renal failure, nonhematologic cancer, and gastrointestinal disease. There was no statistically significant difference in outcome: of the 103 patients treated with amphotericin B, 81 (79 percent) were judged to have been treated successfully, as were 72 of the 103 patients treated with fluconazole (70 percent P = 0.22; 95 percent confidence interval for the difference, -5 to 23 percent). The bloodstream infection failed to clear in 12 patients in the amphotericin group and 15 in the fluconazole group; the species most commonly associated with failure was Candida albicans. There were 41 deaths in the amphotericin group and 34 deaths in the fluconazole group (P = 0.20). Intravascular catheters appeared to be the most frequent source of candidemia. There was less toxicity with fluconazole than with amphotericin B.. In patients without neutropenia and without major immunodeficiency, fluconazole and amphotericin B are not significantly different in their effectiveness in treating candidemia.

Topics: Amphotericin B; Candidiasis; Catheters, Indwelling; Female; Fluconazole; Follow-Up Studies; Fungemia; Humans; Male; Middle Aged; Neutropenia; Treatment Outcome

Topics: Adolescent; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Child; Child, Preschool; Female; Humans; Immunocompromised Host; Infant; Liposomes; Liver Transplantation; Male; Mycetoma; Mycoses

Invasive fungal infection is a problem in patients undergoing bone marrow transplantation (BMT). To determine if a liposomal formulation of amphotericin B (Ambisome) is safe and can prevent fungal infection we performed a placebo controlled double-blind randomized prophylactic trial. Study drug was administered from when neutrophil count had decreased to < 0.5 x 10(9)/l and was continued until neutrophils recovered to this level or an infection or toxicity end-point was reached. Thirty-six patients received 1 mg/kg/day of ambisome and 40 patients received placebo daily. There were no statistical differences in characteristics or clinical course between the two groups. Fungal colonization decreased in the ambisome group while it increased in the placebo group. By the end of prophylaxis 8 of 24 (33%) patients receiving ambisome were colonized compared with 18 of 29 (62%) placebo patients (p = 0.05). Five and 7 patients on ambisome or placebo, respectively, were withdrawn due to a presumed fungal infection (NS). There was no statistical reduction of autopsy-proven fungal infection. Proven fungal infection occurred in one patient receiving ambisome (C. guillermondi) compared with three patients receiving placebo (C. guillermondi, 2; C. albicans, 1). Ambisome was well tolerated at the dose of 1 mg/kg/day but in three patients allergic reactions were observed.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Child; Child, Preschool; Double-Blind Method; Drug Carriers; Drug Hypersensitivity; Drug Tolerance; Female; Humans; Immunocompromised Host; Infant; Liposomes; Male; Middle Aged; Mycoses; Safety

A nonimmunocompromised 32-year-old man with arthrosis of the knee participated as a placebo control in a clinical trial of intraarticular injections of hyaluronan. After the fourth weekly injection of saline, he developed a warm and swollen knee, and synovial fluid cultures revealed growth of Candida albicans. Oral fluconazole treatment was instituted 2 weeks after onset of symptoms, but failed to eradicate the infection. The patient recovered after treatment with local and systemic amphotericin B, systemic 5-fluorocytosine and surgical synovectomy. Quantitation of joint cartilage proteoglycan fragments in synovial fluid indicated extensive breakdown of cartilage during the acute phase of arthritis but, parallel to clinical recovery, these levels returned to normal.

Topics: Adult; Amphotericin B; Arthritis, Infectious; Candida albicans; Candidiasis; Combined Modality Therapy; Double-Blind Method; Drug Therapy, Combination; Flucytosine; Humans; Hyaluronic Acid; Injections, Intra-Articular; Male; Synovectomy

The significance of candiduria in critically ill patients remains unclear. It may represent harmless colonization or a potentially life-threatening infection. We analyzed 47 patients in the surgical intensive care unit (SICU) (trauma: 20, general surgery: 15, neurosurgery: 12) who had candiduria, defined by a colony count greater than 100,000/mL. Twenty-seven of these patients were studied retrospectively. Twenty were evaluated prospectively. All patients were receiving broad-spectrum antibiotics for bacterial infections. Retrospective group: ten patients (group A) did not develop disseminated candidiasis, whereas 17 patients (group B) did. Group B had higher APACHE II scores on admission (13.4 +/- 7.8) and at the time of candiduria (13.7 +/- 4.4) when compared with group A [admission: 5.0 +/- 4.6; candiduria: 6.7 +/- 3.6 (p < 0.02)]. In group B, disseminated candidiasis was not diagnosed and treated until 9.9 +/- 4.4 days after development of candiduria. Prospective group: twenty patients with candiduria were treated with systemic fluconazole (group C) at the time of candiduria. The APACHE II scores of group C on admission (12.8 +/- 3.9) and at the time of candiduria (10.5 +/- 4.0) were comparable with those of group B. No patient in Group C developed disseminated candidiasis. The septic mortality rates of groups A, B, and C were 0%, 53%, and 5%, respectively (p < 0.05-0.0001). In patients exhibiting ongoing sepsis and organ failure (high APACHE scores), candiduria may be an early indicator of systemic infection. Diagnosis of disseminated infection and its treatment may be delayed if conventional criteria for candidiasis (positive blood cultures, multiple site isolation) are awaited.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Amphotericin B; Bacterial Infections; Candidiasis; Cause of Death; Colony Count, Microbial; Critical Illness; Cross Infection; Fluconazole; Fungemia; Hospital Mortality; Humans; Infection Control; Infusions, Intravenous; Middle Aged; Prospective Studies; Retrospective Studies; Risk Factors; Severity of Illness Index; Superinfection; Therapeutic Irrigation; Urinary Tract Infections; Urine

Topics: Adult; Amphotericin B; Anemia, Aplastic; Bone Marrow Transplantation; Candidiasis; Female; Humans; Incidence; Leukemia; Liposomes; Male; Metabolic Diseases; Neoplasms; Transplantation, Autologous; Transplantation, Homologous

Systemic Candida infections are a major cause of infectious morbidity and mortality during chemotherapy-induced neutropenia. Because of the unreliability of conventional diagnostic tests to detect systemic infection early in its course, treatment of established disseminated Candida infection has been generally disappointing with mortality rates of 60-80% in leukemia and bone marrow transplant patients and 30-40% in solid tumor patients. The use of empiric amphotericin B in patients with fever not responding to empiric antibacterial agents has been shown to be successful in reducing morbidity and mortality from fungal infections. However, its toxicity has mitigated the success of this approach. Fluconazole given prophylactically at the institution of chemotherapy has been shown to be a safe and effective alternative. It, however, is not active against all fungal species, especially Aspergillus and some of the less virulent Candida species. Some centers have reported break-through infections by these less susceptible organisms. Whether or not these limitations in its spectrum of activity will limit its usefulness in the future remains unanswered at this time and could pose a cloud to an otherwise bright promise.

Topics: Amphotericin B; Bone Marrow Transplantation; Candidiasis; Disease Susceptibility; Double-Blind Method; Fluconazole; Humans; Immunocompromised Host; Neoplasms; Neutropenia; Survival Rate

Treatment of fungal infections in neutropenic patients continues to be a major problem for the clinician. Treatment of such infections with amphotericin B is difficult, because of its many side-effects. In a neutropenic mouse model, itraconazole appeared to be as effective as amphotericin B against Candida albicans, and was more effective than amphotericin B in treating an Aspergillus infection in a patient with chronic granulomatous disease. In a randomized, comparative trial of itraconazole and amphotericin B as treatment for Candida and Aspergillus infections, 32 neutropenic patients were evaluated. Patients received either oral itraconazole, 200 mg twice daily, intravenous amphotericin B, 0.6 mg/kg/day, or in some cases of Candida infection intravenous amphotericin B, 0.3 mg/kg/day, plus flucytosine, 150 mg/kg/day. The causative organism of fungal infection was Candida spp. in 16 patients and Aspergillus spp. in 13 patients; 27 patients had pneumonia. The median duration of treatment was 13 days with amphotericin B and 20 days with itraconazole. Nine of 16 patients responded to amphotericin B, and 10 of 16 patients responded to itraconazole. Of the patients with Aspergillus infection, 6/8 treated with itraconazole and 2/5 treated with amphotericin B responded. Three patients with Aspergillus infection died in the amphotericin B arm and none in the itraconazole arm; 2 patients treated with itraconazole died from candidal infections. Absorption of itraconazole was unreliable in these seriously ill patients with disturbed gastrointestinal function. These results suggest that itraconazole could be an effective drug against systemic fungal infections in neutropenic patients. One retrospective study also suggest that itraconazole is superior to ketoconazole in prophylaxis for Aspergillus infections. Further studies are needed.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Humans; Itraconazole; Ketoconazole; Mycoses; Neutropenia

This report details the management of a group of newborns who had a diagnosis of systemic Candida albicans septicemia. All the infants were extremely preterm (29 weeks' gestation or less) and had predisposing factors to disseminated fungal infections. Diagnosis was made by cultures from blood, urine, and from the tip of indwelling catheters. Therapy was based in all the infants on the combination of amphotericin B (Amph. B) and 5-fluorocytosine (5FC). Amph. B was intravenously administrated at a test dose of 0.1 mg/kg which if tolerated, was increased with scalar doses until a maximum of 0.35-0.50 mg/kg/die. 5FC was intravenously or orally administered at a 100-200 mg/kg/die dose. Time of treatment with Amph B was prolonged from 13 to 30 days and that with 5FC from 11 to 40 days. In two infants there was an increase of transaminases and Gamma GT and no infant had signs of nephrotoxicity. The high therapeutic success (75% of cases) confirms the validity of the utilized therapeutic schemes.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Flucytosine; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Infusions, Intravenous; Treatment Outcome

Systemic mycosis constitute a serious threat for the patient with granulocytopenia. The most important causative agents are Candida spp., Aspergillus spp. and, to a lesser extent, Cryptococcus neoformans, Mucoraceae and Pseudoallescheria boydii. Treatment of such infections with amphotericin B is difficult, because of the many side-effects of this medicine, such as hypotension, fever, shivering, thrombophlebitis, nephrotoxicity, renal tubular acidosis, hypokalaemia, anaemia and thrombocytopenia. In addition, the efficacy of amphotericin B in the treatment of proven mycotic infections in granulocytopenic patients is not very great. Itraconazole is a new, oral antifungal agent which is active in vitro and in animal experiments against both Candida and Aspergillus. In patients without granulocytopenia, itraconazole appeared to be effective in the treatment of deep Candida and Aspergillus infections. On the basis of the above data, a randomized comparative investigation was carried out unto the efficacy of amphotericin B and itraconazole in the treatment of systemic mycoses in neutropenic patients.

Topics: Adolescent; Agranulocytosis; Amphotericin B; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Candidiasis; Humans; Itraconazole; Ketoconazole; Male; Mycoses

One hundred and twenty-six patients were treated for 137 episodes of fungal infection with liposomal amphotericin B (AmBisome) at 43 investigational centres. Among the patients were 72 with malignancies, 17 organ transplant recipients, 20 patients with immunological disorders and 17 others. AmBisome treatment was instituted after toxicity from previous amphotericin B treatment in 49 cases, nephrotoxicity or renal insufficiency in 40 and failure of previous antifungal treatment in 41. One hundred and eight episodes were clinically evaluable; among these 52 were caused by Candida spp. and 34 by Aspergillus spp. Ninety-nine patients were treated for at least eight days with a maximum dose of 0.7-5 mg/kg/day. Among 64 cases with proven invasive fungal infection 58% were cured. Fungi were eradicated in 35 of 54 (65%) mycologically evaluable cases. The cumulative dose was 3.2 +/- 3.2 (mean +/- S.D.) in cases where fungi were eradicated in comparison with 3.3 +/- 2.3 g in cases where fungi persisted. The eradication rate was 83% for Candida spp. compared with 41% for Aspergillus spp. (P less than 0.01). Among 24 cases with presumptive invasive fungal infections 14 (58%) were cured. Candida spp. were eradicated in seven of ten of these cases. Among 11 cases with superficial fungal infections eight were cured and three improved. Candida spp. were eradicated in four of five patients. It is concluded that AmBisome is an effective antifungal agent in a majority of patients with invasive or superficial fungal infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Aspergillosis; Candidiasis; Child; Child, Preschool; Drug Carriers; Drug Evaluation; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Liposomes; Male; Middle Aged; Mycoses

In a randomised clinical trial, we compared the efficacy of the new triazole drug itraconazole (200 mg orally twice daily) with that of amphotericin B (0.6 mg/kg daily or 0.3 mg/kg in combination with flucytosine) in neutropenic (less than 500 x 10(6)/l neutrophils) patients with proven or highly suspected systemic fungal infections. Patients with unexplained fever alone were not included in the study. Of the 40 patients enrolled, 32 patients (16 males, 16 females) were evaluable. Sixteen patients (median age 49 years) were treated with itraconazole for a median period of 20 days and 16 patients (median age 32 years) received amphotericin B for a median period of 13 days. The overall clinical response was 10/16 (63%) for patients treated with itraconazole and 9/16 (56%) for patients treated with amphotericin B (P greater than 0.90). Itraconazole seemed to be more effective against Aspergillus infections, whereas amphotericin B seemed to be more effective against candidal infections, although the differences were not statistically significant.

Topics: Amphotericin B; Aspergillosis; Aspergillus fumigatus; Candidiasis; Drug Therapy, Combination; Female; Flucytosine; Humans; Itraconazole; Ketoconazole; Male; Middle Aged; Neutropenia; Prospective Studies

To study the efficacy of fluconazole against chronic disseminated candidiasis (hepatosplenic candidiasis) in patients with leukemia in whom amphotericin B treatment had failed.. Retrospective analysis of patients with chronic disseminated candidiasis treated with fluconazole on a compassionate investigational new drug protocol.. Multi-institutional.. Twenty consecutive patients received 100 to 400 mg of fluconazole per day for a median of 30 weeks. All had either failed to respond to treatment with more than 2 g of amphotericin B or had serious amphotericin B-related toxicities.. Fourteen of 16 evaluable patients (88%) responded. Responses were observed in seven of nine patients in whom adequate doses of amphotericin B had failed and in all seven patients who had amphotericin B-related toxicities. In 12 patients, cytotoxic chemotherapy was continued without flare of the infection. Fluconazole was well tolerated with rare side effects. Aspergillus superinfection developed in three patients and contributed to the death of two of them.. Fluconazole is a safe and effective agent with significant activity against chronic disseminated candidiasis.

Topics: Adult; Aged; Amphotericin B; Candidiasis; Child, Preschool; Chronic Disease; Female; Fluconazole; Humans; Leukemia, Myeloid, Acute; Liver Diseases; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Retrospective Studies; Splenic Diseases; Superinfection

Systemic fungal infections are recognized at increasing frequency during the course of intensive therapy for acute leukemias and require parenteral antifungal treatment mostly by amphotericin B (ampho B) alone or in combination with 5-Fluorocytosine (5-FC). Because of the potential myelosuppressive side effects of 5-FC it was the aim of the current study to evaluate the recovery of hematopoietic cells after intensive antileukemic therapy in patients receiving ampho B and 5-FC treatment for proven or suspected systemic fungal infections. The study population comprised 87 patients who were treated by standard chemotherapy for acute myeloid leukemia (AML) at first diagnosis or relapse. Twenty-two patients underwent systemic antifungal therapy consisting of ampho B (3 to 10 mg/kg/d) and 5-FC (150 mg/kg/d) for 3 to 33 days (median, 12 days). The remaining 65 patients served as controls to assess the hematologic recovery time (TR) as defined by the interval between the onset of chemotherapy and the post-treatment rise of granulocyte levels to greater than 500 cmm and thrombocyte levels to greater than 20,000 cmm. In patients receiving antifungal therapy, a significant prolongation of TR was observed with a median TR of 29 days compared with a median TR of 24 days (P = 0.0016) for the control group. No correlation was found between TR and the total dose of either ampho B or 5-FC or the type of antileukemic regimen. A possibly direct myelosuppressive effect of a fungal infection was unlikely to explain the findings because the ampho B/5-FC treatment was started in patients with proven or only suspected fungal infections, causing a similar delay of TR in both groups. The present data strongly suggest a myelosuppressive effect of ampho B/5-FC antifungal treatment in patients after intensive chemotherapy for acute leukemias.

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Antineoplastic Agents; Candidiasis; Drug Administration Schedule; Drug Therapy, Combination; Flucytosine; Hematopoiesis; Humans; Immune Tolerance; Leukemia, Myeloid; Middle Aged; Random Allocation

Invasive candidiasis infections remain a major complication in I.C.U. patients. Numerous attempts have been made to evaluate potential prophylactic methods. Various agents have been tested. Gastrointestinal tract constitutes one of the major reservoirs for Candida species. One major problem is the difficulty in establishing an accurate, early, diagnosis of invasive fungal infection. A prospective randomized, controlled blind study was performed to assess the ability of oral Amphotericin B to prevent candidiasis in selected I.C.U. patients. Fifty one patients with serious infection and antibiotherapy were randomized to receive either oral Amphotericin B (2 g/day) or placebo, and observed until discharge. All patients were screened weekly for sites culture positive, sero-conversion and oesophagitis. Invasive candidiasis developed in 45% of patients receiving Amphotericin B compared with 41% receiving placebo. C. Albicans persists in the surveillance cultures. However a significant reduction of the colonization by the yeasts and a significant reduction of oesophagitis was demonstrated among the Amphotericin B group. No benefit was found in the total number of hospital days. Digestive decontamination can be successfully managed by Amphotericin B in I.C.U. patients but failed to prevent invasive candidiasis.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Candidiasis; Clinical Protocols; Cross Infection; Digestive System; Esophagitis; Female; Humans; Intensive Care Units; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cryptococcosis; Drug Synergism; Drug Therapy, Combination; Flucytosine; Humans; Mycoses; Prospective Studies; Rifampin

Thirty-three (0.7%) of 4,818 trauma patients admitted between January 1, 1987, and July 1, 1989, developed invasive candidosis requiring IV antifungal therapy. All patients were seriously traumatized. Before developing candidosis, all patients had documented bacterial infections. These infections were generally polymicrobial and were treated with multiple broad-spectrum antibiotics (an average of 5.4 antibiotics for 17.2 days). Twenty-eight (85%) of 33 patients received enteral feedings for an average of 11 days +/- 1.5 (SEM) before developing candidosis and 24 (73%) received NG/oral nystatin for an average of 7.6 days +/- 0.9 before developing candidosis. All patients with candidosis were treated with intravenous amphotericin B: cumulative dose of 157.3 mg +/- 31.3 mg given over 10 days +/- 1.1. One patient developed recurrent candidosis despite NG/oral prophylaxis and enteral feedings. Six patients (18%) died due to sepsis and multiple organ failure. The patients who died did not objectively differ from the survivors. Candidosis is an infrequent infection in severely injured patients. Candidosis was invariably preceded by treatment with multiple broad-spectrum antibiotics for a variety of polymicrobial bacterial infections. NG/oral nystatin and enteral feedings did not prevent candidosis, in contrast to widely accepted beliefs. Amphotericin B therapy was safe. Recurrent candidosis was unusual. Candida infections had a high mortality rate associated with multiple blood transfusions and prolonged hospitalization. Candidosis represents a sign of severe injury and illness but can be amenable to prompt, aggressive treatment.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Female; Humans; Male; Middle Aged; Prospective Studies; Retrospective Studies; Wounds and Injuries

The effectiveness of treatment of candidiasis of the esophagus by different methods and preparations (nystatin, amphotericin B, donor leukocytic mass) was compared in 34 patients. Local application of amphotericin B and donor leukocytic mass was found the most effective in the combined treatment of candidiasis of the esophagus.

Topics: Adult; Amphotericin B; Blood Transfusion; Candidiasis; Clinical Trials as Topic; Esophagitis; Female; Humans; Leukocyte Transfusion; Male; Middle Aged; Nystatin

Of 224 consecutive renal transplant patients in a prospective, randomized immunosuppressive trial, candida esophagitis developed in 5 despite nystatin prophylaxis. No differences were noted between cyclosporine and antilymphocyte globulin-azathioprine immunosuppressive treatment. All patients were diabetic, and four were recipients of cadaver kidneys. Candida esophagitis occurred within 6 months after transplantation, and only one patient had recurrence. All patients responded to treatment consisting of 2 to 6 days of intravenous amphotericin B (0.2 to 2 mg/kg total dose). The prevalence of candida esophagitis was not related to rejection episodes. Three of five patients eventually died, one 2 weeks after resolution of candida esophagitis from a hypoglycemic episode, one from acute exacerbation of pulmonary failure and relapsing pancreatitis in association with candida esophagitis and therapy-resistant candidemia, and one 17 months after candida esophagitis from pulmonary edema. Our findings show that candida esophagitis by itself is an easily managed complication, but is also a sign of potentially increased morbidity in these patients.

Topics: Adult; Amphotericin B; Antilymphocyte Serum; Azathioprine; Candidiasis; Clinical Trials as Topic; Cyclosporins; Esophagitis; Female; Humans; Kidney Transplantation; Male; Minnesota; Nystatin; Prospective Studies; Random Allocation

Previous observations suggest that tubulo-glomerular feedback could be involved in amphotericin B nephrotoxicity. We then investigated the influence of sodium status on the occurrence of renal damage during amphotericin B therapy. A retrospective survey demonstrated that impaired renal function occurred during therapy in 67 per cent of the patients who received amphotericin B alone and in 12 per cent of the patients who received amphotericin B and ticarcillin (parenteral sodium supplement of 100-150 meq per day). Prospective studies were then undertaken both in adults and children. Intravenous sodium supplement was given intravenously as routine prophylaxis with amphotericin B therapy. In all courses amphotericin B was successfully administered without deterioration in renal function. These results support the hypothesis that parenteral sodium supplementation reduces the frequency of developing impaired renal function during amphotericin B therapy.

Topics: Adult; Amphotericin B; Candidiasis; Clinical Trials as Topic; Female; Humans; Infant, Newborn; Kidney; Kidney Diseases; Male; Prospective Studies; Retrospective Studies; Sodium

As invasive fungal infection remains a common problem in the management of cancer patients, chemoprophylaxis of these opportunistic infections is desperately needed. The most frequently investigated antifungal agents have been nystatin, amphotericin B, and ketoconazole. In placebo-controlled studies, high doses of antifungal agents decreased the positive results from surveillance cultures, and there is some suggestion that such chemoprophylaxis may reduce the incidence of invasive candidiasis in neutropenic cancer patients. However, no oral chemoprophylaxis has effectively prevented aspergillosis or mucormycoses in these patients. There are still many areas of controversy, and the most adequate regimens, if any, remain to be defined.

Topics: Administration, Oral; Administration, Topical; Amphotericin B; Antifungal Agents; Candidiasis; Clinical Trials as Topic; Humans; Ketoconazole; Miconazole; Mycoses; Neoplasms; Nystatin

The prevention of fungal infections in granulocytopenic patients seems necessary to improve the final outcome of neoplastic patients. In particular, aspergillosis and candidiasis represent common life-threatening infections among the patients with acute hematological malignancies. Despite extensive investigations during this last decade, the optimal approaches to prevent these complications are still controversial. This situation probably reflects and stresses the numerous factors which predispose to these opportunistic fungal infections. Therefore, the effective prophylaxis of candidiasis and aspergillosis should result from the use of basic and specific approaches. General and simple measures including well trained personnel (physicians, nurses but also individuals in charge of the housekeeping, etc.), careful patient teaching of personal hygiene and control of the food intake (limited to cooked food diet), will reduce the acquisition of potential fungal pathogens. Moreover, the isolation in a laminar air flow room seems to be the optimal specific technique to prevent the colonization as well as the development of pulmonary aspergillosis. The meticulous evaluation of the respiratory sinus status as well as surveillance cultures obtained from the nose have been shown to be helpful to predict patients at high risks. Until now, there is no systemic chemoprophylaxis available to decrease the incidence of invasive aspergillosis. However, the topical application of antifungal agent using nasal spray or aerosols should be further investigated. Exogenous candidiasis such as catheter or TPN products related yeast infections can be avoided by aseptic manipulations. Endogenous candidiasis, resulting from the dissemination of the yeasts from the gastro-intestinal tract (which represents the major reservoir), are still much more difficult to prevent.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Agranulocytosis; Amphotericin B; Aspergillosis; Candidiasis; Clinical Trials as Topic; Humans; Ketoconazole; Neoplasms; Neutropenia; Nystatin; Patient Isolation

In a prospective study the efficacy of two regimens for selective decontamination of the digestive tract was studied in patients with acute leukaemia during remission induction therapy. Seventy-eight patients were randomized to receive either a combination of cotrimoxazole, polymyxin B and nystatin (group A) or a combination of nalidixic acid, polymyxin B, neomycin and nystatin. With both regimens the gastrointestinal tract could be decontaminated equally effectively from potential pathogens. In the oropharyngeal region the decontamination from Enterobacteriaceae was significantly better in group A (P less than 0.01). In both groups less than 10% of the acquired infections were caused by gram-negative bacilli and no gram-negative septicaemia occurred in either group. The median time interval until the first acquired infection was 17 days in group A and 36 days in group B, respectively (P less than 0.05). It is concluded that regimen A might be more effective than regimen B though both regimens prevent reliably severe gram-negative infections.

Topics: Acute Disease; Adolescent; Adult; Aged; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Cephalosporins; Enterobacteriaceae Infections; Female; Flucytosine; Humans; Leukemia; Male; Middle Aged; Oxacillin; Penicillins; Prospective Studies; Staphylococcal Infections; Streptococcal Infections

To determine the incidence of hematogenous candida endophthalmitis in seriously ill patients given parenteral hyperalimentation fluids, 131 hyperalimented postoperative patients were prospectively evaluated. All patients were screened weekly for the development of chorioretinal lesions, blood cultures positive for Candida albicans, and signs and symptoms of candida infection. Thirteen (9.9%) of 131 patients developed chorioretinal lesions compatible with hematogenous candida endophthalmitis. Seven of the 13 patients with eye lesions had blood cultures positive for yeast, whereas only two of 118 without eye lesions had blood cultures positive for yeast (P less than 0.0005). Thus, the occurrence of eye lesions consistent with hematogenous candida endophthalmitis correlated with positive blood cultures for yeast and strongly suggested invasive candidiasis.

Topics: Amphotericin B; Candidiasis; Candidiasis, Oral; Chorioretinitis; Culture Media; Endophthalmitis; Gastrointestinal Hemorrhage; Humans; Intertrigo; Parenteral Nutrition; Parenteral Nutrition, Total; Urinary Tract Infections; Wound Infection

Autopsy examinations were conducted in 72 patients with hematologic malignant neoplasms who received antibacterial therapy before their deaths. These patients were participants in a large double-blind study designed to assess the efficacy of oral amphotericin B in decreasing the incidence of candidal infection. The patients received either 50 mg of amphotericin B orally four times a day, or they received a matching placebo. Eight of 33 patients (24%) who had received placebo and two of 39 (5%) who had received amphotericin had histopathologic evidence of disseminated candidiasis. We conclude that in these patients with hematologic malignant neoplasms who received antibiotics within two weeks of death, the concomitant oral administration of amphotericin was effective in decreasing the incidence of systemic candidal infections, indicating that the gastrointestinal tract serves as a portal of entry for Candida albicans.

Topics: Administration, Oral; Adult; Aged; Amphotericin B; Autopsy; Candidiasis; Clinical Trials as Topic; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged

Topics: Amphotericin B; Candidiasis; Drug Evaluation; Drug Interactions; Drug Therapy, Combination; Humans; Imidazoles; In Vitro Techniques; Miconazole

Topics: Adult; Amphotericin B; Candidiasis; Candidiasis, Vulvovaginal; Clinical Trials as Topic; Drug Evaluation; Exanthema; Female; Humans; Leukorrhea; Nystatin; Pregnancy; Pruritus

Topics: Amphotericin B; Bromides; Candida; Candidiasis; Clinical Trials as Topic; Drug Synergism; Humans; Quinolines; Tetracycline

Candida lusitaniae is an uncommon pathogen that accounts for approximately 1% of patients with candidiasis. In this report, we present the case of a 24-year-old woman with severe pancreatitis who was emergently admitted to Northern Yokohama Hospital. We started treating the pancreatitis and infections according to her culture results. However, her symptoms, accompanied by a necrotic pancreas, did not improve. Finally, C. lusitaniae was detected in the blood and catheter samples. We started antifungal treatment according to the culture results, but the patient died. Generally, the mortality rate for acute pancreatitis ranges from 3% for patients with interstitial edematous pancreatitis to 17% for those who develop pancreatic necrosis. Although we chose appropriate antibiotics and antifungal agents based on the culture results, the treatments failed. Early detection, sufficient doses of antimicrobials and frequent monitoring using sample culture are crucial because infection control may be inadequate, especially in tissues with low blood flow, such as necrotic tissues.

Topics: Acute Disease; Adult; Antifungal Agents; Candida; Candidiasis; Female; Humans; Pancreatitis; Young Adult

Topics: Amphotericin B; Antifungal Agents; Candida; Candida auris; Candidiasis; Humans; Microbial Sensitivity Tests

Fungal implant-associated bone infections are rare but difficult to treat and often associated with a poor outcome for patients. Candida species account for approximately 90% of all fungal infections. In vivo biofilm models play a major role to study biofilm development and potential new treatment options; however, there are only a very few in vivo models to study fungi-associated biofilms. Furthermore, mammalian infection models are replaced more and more due to ethical restrictions with other alternative models in basic research. Recently, we developed an insect infection model with Galleria mellonella larvae to study biofilm-associated infections with bacteria. Here, we further expanded the G. mellonella model to study in vivo fungal infections using Candida albicans and Candida krusei. We established a planktonic and biofilm-implant model to test different antifungal medication with amphotericin B, fluconazole, and voriconazole against the two species and assessed the fungal biofilm-load on the implant surface. Planktonic infection with C. albicans and C. krusei showed the killing of the G. mellonella larvae at 5 × 10

Topics: Amphotericin B; Animals; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Fluconazole; Humans; Larva; Mammals; Microbial Sensitivity Tests; Voriconazole

During the COVID-19 pandemic in Qatar, many patients who were severely ill were colonized and infected by Candida auris, an invasive multidrug-resistant yeast pathogen that spreads through nosocomial transmission within healthcare facilities. Here, we investigated the molecular epidemiology of these C. auris isolates and the mechanisms associated with antifungal drug resistance.. Whole genomes of 76 clinical C. auris isolates, including 65 from patients with COVID-19 collected from March 2020 to June 2021, from nine major hospitals were sequenced on Illumina NextSeq. Single nucleotide polymorphisms were used to determine their epidemiological patterns and mechanisms for antifungal resistance. The data were compared with those published prior to the COVID-19 pandemic from 2018 to 2020 in Qatar.. Genomic analysis revealed low genetic variability among the isolates from patients with and without COVID-19, confirming a clonal outbreak and ongoing dissemination of C. auris among various healthcare facilities. Based on antifungal susceptibility profiles, more than 70% (22/28) of isolates were resistant to both fluconazole and amphotericin B. Variant analysis revealed the presence of multi-antifungal resistant isolates with prominent amino acid substitutions: Y132F in ERG11 and V704L in CDR1 linked to reduced azole susceptibility and the emergence of echinocandin resistance samples bearing mutations in FKS1 in comparison with pre-COVID-19 pandemic samples. One sample (CAS109) was resistant to three classes of antifungal drugs with a unique premature stop codon in ERG3 and novel mutations in CDR2, which may be associated with elevated amphotericin B and azole resistance.. Candida auris isolates from patients with COVID-19 and from most patient samples without COVID-19 in Qatar were highly clonal. The data demonstrated the emergence of multidrug-resistant strains that carry novel mutations linked to enhanced resistance to azoles, echinocandins, and amphotericin B. Understanding the epidemiology and drug resistance will inform the infection control strategy and drug therapy.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candida auris; Candidiasis; COVID-19; Drug Resistance, Fungal; Echinocandins; Humans; Microbial Sensitivity Tests; Pandemics; Qatar

Opportunistic fungal infections by. Over a period of three years, 325 cancer patients suspected to. Seventy-four cancer patients had. The findings of the present work shows a warning increase in resistance to echinocandins. Since all fluconazole resistance isolates were obtained from candidemia, we recommend amphotericin B as the first line therapy for this potentially fatal infection.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Candida; Candidemia; Candidiasis; Drug Resistance, Fungal; Fluconazole; Humans; Itraconazole; Microbial Sensitivity Tests; Neoplasms

Candida auris is a multidrug-resistant pathogen that causes nosocomial outbreaks and high mortality. We conducted this study to investigate the molecular mechanisms of antifungal resistance in our clinical isolate of C. auris with a high level of resistance to three main classes of antifungals.. A clinical C. auris isolate was identified by MALDI-TOF MS and antifungal susceptibilities were determined by the Sensititre YeastOne YO10 panel. After sequencing the whole genome of the microorganism with Oxford Nanopore NGS Technologies, a phylogenetic tree was drawn as a cladogram to detect where the C. auris clade to this study's assembly belongs.. The C. auris isolate in this study (MaCa01) was determined to be a part of the clade I (South Asian). The resistance-related genes indicated that MaCa01 would most likely be highly resistant to fluconazole (CDR1, TAC1b, and ERG11), none or little resistant to amphotericin B (AmpB) and echinocandins, and sensitive to flucytosine. The mutations found in the above-mentioned genes in the Türkiye C. auris isolate reveals an antifungal resistance pattern. This molecular resistance pattern was found consistent with the interpretation of MIC values of the antifungals according to CDC tentative breakpoints.. We detected the well-known antifungal resistance mutations, responsible for azole resistance in C. auris. Despite no ERG2, ERG6, and FKS mutation identified, the isolate was found to be resistant to AmpB and caspofungin based on the CDC tentative breakpoints which could be related to unidentified mutations.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida auris; Candidiasis; Drug Resistance, Fungal; Humans; Microbial Sensitivity Tests; Phylogeny; Tertiary Care Centers

In recent decades, Candida albicans have been the main etiological agent of life-threatening invasive infections, characterized by various mechanisms of resistance to commonly used antifungals. One of the strategies to fight Candida infections may be the use of an electromagnetic field. In this study, we examined the influence of the alternating magnetic field of 50 Hz on the cells of C. albicans. We checked the impact of the alternating magnetic field of 50 Hz on the viability, filamentation and sensitivity to fluconazole and amphotericin B of two, differing in hydrophobicity, strains of C. albicans, CAF2-1 and CAF 4-2. Our results indicate that using the alternating magnetic field of 50 Hz reduces the growth of C. albicans. Interestingly, it presents a stronger effect on the hydrophobic strain CAF4-2 than on the hydrophilic CAF2-1. The applied electromagnetic field also affects the permeabilization of the cell membrane. However, it does not inhibit the transformation from yeast to hyphal forms. AMF is more effective in combination with fluconazole rather than amphotericin B. Our findings confirm the hypothesis that the application of the alternating magnetic field of 50 Hz in antifungal therapy may arise as a new option to support the treatment of Candida infections.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Fluconazole; Humans; Hydrophobic and Hydrophilic Interactions; Magnetic Fields; Microbial Sensitivity Tests

The emergence of drug-resistant fungal pathogens poses great threats to an increasing number of vulnerable populations worldwide, and the need for novel antifungal agents is imperative. In this work, a series of lipo-γ-AA peptides were synthesized and evaluated for their biological activities. One lead, MW

Topics: Animals; Antifungal Agents; Candida albicans; Candidiasis; Drug Resistance, Fungal; Fluconazole; Mice; Microbial Sensitivity Tests; Peptides

The need for pediatric antifungal stewardship programs has been driven by an increasing consumption of antifungals for prophylactic and empirical use. Drivers and rational of antifungal prescribing need to be identified to optimize prescription behaviors.. A prospective modified weekly Point Prevalence Survey capturing antifungal prescriptions for children (> 90 days to < 18 years of age) in 12 centers in England during 26 consecutive weeks was performed. Demographic, diagnostic and treatment information was collected for each patient. Data were entered into an online REDCap database.. One thousand two hundred fifty-eight prescriptions were included for 656 pediatric patients, 44.9% were girls, with a median age of 6.4 years (interquartile range, 2.5-11.3). Most common underlying condition was malignancy (55.5%). Four hundred nineteen (63.9%) received antifungals for prophylaxis, and 237 (36.1%) for treatment. Among patients receiving antifungal prophylaxis, 40.2% did not belong to a high-risk group. In those receiving antifungal treatment, 45.9%, 29.4%, 5.1% and 19.6% had a diagnosis of suspected, possible, probable of proven invasive fungal disease (IFD), respectively. Proven IFD was diagnosed in 78 patients, 84.6% (n = 66) suffered from invasive candidiasis and 15.4% (n = 12) from an invasive mold infection. Liposomal amphotericin B was the most commonly prescribed antifungal for both prophylaxis (36.6%) and empiric and preemptive treatment (47.9%). Throughout the duration of the study, 72 (11.0%) patients received combination antifungal therapy.. Antifungal use in pediatric patients is dominated by liposomal amphotericin B and often without evidence for the presence of IFD. A significant proportion of prophylactic and empiric antifungal use was seen in pediatric patients not at high-risk for IFD.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Antimicrobial Stewardship; Antiprotozoal Agents; Azoles; Candidiasis; Candidiasis, Invasive; Child; Child, Preschool; England; Female; Humans; Invasive Fungal Infections; Liposomes; Male; Prescriptions; Prospective Studies

Corneal ulcers, a leading cause of blindness in the developing world are treated inappropriately without prior microbiology assessment because of issues related to availability or cost of accessing these services. In this work we aimed to develop a device for identifying the presence of Gram-positive or Gram-negative bacteria or fungi that can be used by someone without the need for a microbiology laboratory. Working with branched poly (N-isopropyl acrylamide) (PNIPAM) tagged with Vancomycin, Polymyxin B, or Amphotericin B to bind Gram-positive bacteria, Gram-negative bacteria and fungi respectively, grafted onto a single hydrogel we demonstrated specific binding of the organisms. The limit of detection of the microbes by these polymers was between 10 and 4 organisms per high power field (100X) for bacteria and fungi binding polymers respectively. Using ex vivo and animal cornea infection models infected with bacteria, fungi or both we than demonstrated that the triple functionalised hydrogel could pick up all 3 organisms after being in place for 30 min. To confirm the presence of bacteria and fungi we used conventional microbiology techniques and fluorescently labelled ligands or dyes. While we need to develop an easy-to-use either a colorimetric or an imaging system to detect the fluorescent signals, this study presents for the first time a simple to use hydrogel system, which can be applied to infected eyes and specifically binds different classes of infecting agents within a short space of time. Ultimately this diagnostic system will not require trained microbiologists for its use and will be used at the point-of-care.

Topics: Acrylic Resins; Amphotericin B; Animals; Anti-Bacterial Agents; Bacteria; Candidiasis; Corneal Ulcer; Eye Infections, Bacterial; Eye Infections, Fungal; Fungi; Humans; Hydrogels; Ligands; Microbial Sensitivity Tests; Polymyxin B; Pseudomonas Infections; Rabbits; Staphylococcal Infections; Vancomycin

Coronavirus disease 2019 (COVID-19), which is attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been causing a worldwide health issue. Airways colonization by Candida spp. is prevalent among patients on automatic ventilation in intensive care units (ICUs). This research aimed to ascertain the risk factors and roles of Candida spp. respiratory tract colonization, and Candida lung infection during the progression of COVID-19 pneumonia in critically ill patients. In total, Candida spp. were recovered in 69 from 100 immunosuppressed patients with COVID-19. Bronchoscopy was used to collect the Bronchoalveolar lavage (BAL) specimens. For the identification of Candida spp. PCR sequencing was done using the ITS1 and ITS4 primers. The amplification of the HWP1 gene was conducted to identify the Candida albicans complex. The antifungal activities of fluconazole, itraconazole, voriconazole, amphotericin B and caspofungin against Candida spp. were evaluated using the Clinical and Laboratory Standards Institute M60. In 63.77% of the patients, Candida respiratory colonization at D0 and D14 had no impact on the severity of COVID-19. In comparison to C. albicans strains, Candida respiratory disorder with C. glabrata had influenced the severity of COVID-19 for critically ill patients following adjustment for the risk factors of COVID-19 (P < 0.05). Amphotericin B and caspofungin showed superior activity against all Candida spp. All antifungal agents showed 100% sensitivity against the two C. africana strains. Our observation on patients who used automatic ventilation, respiratory colonization by Candida spp. was not seen to influence the infection or death caused by COVID-19. Amphotericin B and caspofungin showed superior activity against all Candida spp. and were recommended for the treatment regime of pulmonary candidiasis associated with COVID-19 infection. Although "Candida pneumonia" is rarely being reported in critically ill patients, Candida airway colonization mainly by Candida albicans is common especially among patients with diabetes, malignancies, and kidney disorders.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candidiasis; Caspofungin; COVID-19; Critical Illness; Fluconazole; Humans; Lung; Microbial Sensitivity Tests; Pneumonia; SARS-CoV-2

We report here for the first time the presence of Candida parapsilosis isolates harbouring the Y132F ERG11 gene substitution in patients admitted to a Spanish hospital.. We studied the available (n = 104) C parapsilosis isolates from patients admitted to the Son Espases reference hospital in the Balearic Islands from 1 April 2019 to 30 November 2020. Isolates were sourced from 70 patients: catheter (n = 41), blood cultures (n = 37), lower respiratory tract (n = 15), intra-abdominal (n = 8), and other samples (n = 3). Isolates were genotyped and tested for antifungal susceptibilities to amphotericin B, triazoles, anidulafungin, and micafungin using EUCAST E.Def 7.3.2. The ERG11 gene was sequenced in fluconazole-resistant isolates.. Among the 104 isolates, fluconazole and voriconazole resistance was found in 87 (84%) and 30 (29%) isolates, respectively; all isolates were fully susceptible to echinocandins and amphotericin B. All fluconazole-resistant isolates harboured the Y132F substitution in the ERG11 gene and were grouped into 11 clonally related genotypes. A genotype accounted for 70% (61/87) of fluconazole-resistant isolates. Genotypes involving the fluconazole-resistant isolates were different from those found in the remaining fluconazole-susceptible genotypes. Fifty-six patients harboured fluconazole-resistant genotypes, and 35 of the 56 had candidaemia (48%), abdominal candidiasis (17%), or other forms of candidiasis (35%). Only 20% of the study patients infected by fluconazole-resistant genotypes had a history of azole use.. Fluconazole resistance in C parapsilosis isolates from patients admitted to this reference hospital is not attributable to prior azole use, but rather to the presence of a group of fluconazole-resistant C parapsilosis genotypes that have become endemic.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida parapsilosis; Candidiasis; Drug Resistance, Fungal; Fluconazole; Genotype; Humans; Microbial Sensitivity Tests; Spain

Candida auris is an emerging multidrug-resistant human fungal pathogen often refractory to treatment by all classes of antifungal drugs. Amphotericin B (AmB) is a fungicidal drug that, despite its toxic side effects, remains a drug of choice for the treatment of drug-resistant fungal infections, including those caused by C. auris. However, the molecular mechanisms underlying AmB resistance are poorly understood. In this study, we present data that suggests membrane lipid alterations and chromatin modifications are critical processes that may contribute to or cause adaptive AmB resistance in clinical C. auris isolates. To determine the plausible cause of increased AmB resistance, we performed RNA-seq of AmB-resistant and sensitive C. auris isolates. Remarkably, AmB-resistant strains show a pronounced enrichment of genes involved in lipid and ergosterol biosynthesis, adhesion, drug transport as well as chromatin remodeling. The transcriptomics data confirm increased adhesion and reduced lipid membrane permeability of AmB-resistant strains compared to the sensitive isolates. The AmB-resistant strains also display hyper-resistance to cell wall perturbing agents, including Congo red, calcofluor white and caffeine. Additionally, we noticed an increased phosphorylation of Mkc1 cell integrity MAP kinase upon AmB treatment. Collectively, these data identify differences in the transcriptional landscapes of AmB-resistant versus AmB-sensitive isolates and provide a framework for the mechanistic understanding of AmB resistance in C. auris.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida auris; Candidiasis; Drug Resistance, Fungal; Humans; Lipids; Microbial Sensitivity Tests; Transcriptome

The aim of the study was to investigate the Candida species distribution and their antifungal sensitivities, clinical characteristics, and risk factors of the critically ill patients with invasive Candida infections in a tertiary hospital.. Candida strains from critically ill patients were isolated in a tertiary hospital of Anhui Province from June 2019 to June 2020 through fungal cultures and identified with MALDI-TOF MS system. The antifungal susceptibility was measured by ATB Fungus-3 method. Demographic information and laboratory data were retrieved from the computerized hospital data system.. Candida albicans (C. albicans, 41.49%) was the predominant species in sterile body sites of critically ill patients developing invasive candidiasis, followed by C. glabrata (24.47%) and C. tropicalis (20.21%). The specimen sources were mainly urine (47.87%), then bronchoalveolar lavage fluid (18.09%) and blood (14.89%). In vitro, common Candida species were observed to be highly sensitive to amphotericin B and 5-fluorocytosine. All C. albicans exhibited susceptibility to both fluconazole and voriconazole, as did C. glabrata and C. parapsilosis. However, some C. tropicalis identified were frequently resistant to fluconazole, itraconazole, and voriconazole. The rate of Candida infection was positively correlated with certain risk factors including invasive interventions, age, length of stay in hospital, etc. Conclusions: C. albicans was the main species of invasive Candida infections in critically ill patients, followed by C. glabrata and C. tropicalis. Candida spp. showed the highest rate (10.60%) of resistance to fluconazole, followed by itraconazole (5.30%), voriconazole (5.30%), and 5-fluorocytosine (1.10%). All invasive Candida isolates were sensitive to amphotericin B. In addition, several C. tropicalis were tested and exhibited a high-level resistance to azoles. Notably, a variety of specific risk factors for candidiasis were identified in critically ill patients which need to be taken into consideration.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Candidiasis, Invasive; Critical Illness; Drug Resistance, Fungal; Fluconazole; Flucytosine; Humans; Itraconazole; Microbial Sensitivity Tests; Risk Factors; Voriconazole

Although Amphotericin B (AMB) is considered the most effective anti-mycotic agent for treating Candida infections, its clinical use is limited due to its high toxicity. To address this issue, we developed cholesterol-based dendritic micelles of hyperbranched polyglycerol (HPG), including cholesterol-cored HPG (Chol-HPG) and cholesterol end-capped HPG (HPG@Chol), for AMB delivery. The findings suggested that the presence of cholesterol moieties could control AMB loading and release properties. Dendritic micelles inhibited AMB hemolysis and cytotoxicity in HEK 293 and RAW 264.7 cell lines while increasing antifungal activity against C. albicans biofilm formation. Furthermore, significantly lower levels of renal and liver toxicity biomarkers compared to Fungizone® ensured AMB-incorporated dendritic micelle biosafety, which was confirmed by histopathological evaluations. Overall, the Chol-HPG and HPG@Chol dendritic micelles may be a viable alternative to commercially available AMB formulations as well as an effective delivery system for other poorly soluble antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Glycerol; HEK293 Cells; Humans; Micelles; Polymers

Amphotericin B (AmB) is a widely used antifungal agent especially for the therapy of systemic fungal infections. However, the severe side effects of AmB often leads to the premature termination of the treatment. So it is imperative to find the drugs that can both reduce the dosage and enhance the antifungal efficacy of AmB. Here we demonstrated that Nicotinamide (NAM), a cheap and safe vitamin, could enhance the antifungal activities of AmB. We demonstrated the synergistic interaction of NAM and AmB against

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Humans; Microbial Sensitivity Tests; Niacinamide

We aimed to detect possible changes in Candida species distribution over time and to know the antifungal susceptibility profile of isolates obtained from patients with bloodstream infection (BSI) due to this pathogen. Risk factors associated with 30-day mortality were also assessed. We conducted a retrospective cohort study of patients diagnosed with Candida BSI at a Japanese university hospital from 2013 to 2021. The change in the distribution pattern of the Candida spp. isolated was examined by considering three successive sub-periods of 3 years each. Risk factors for 30-day mortality were determined using Cox regression analysis. In the entire study period, Candida albicans was the most frequent species (46.7%), followed by Candida glabrata (21.5%) and Candida parapsilosis (18.7%). There was no change in Candida species distribution comparing the three sub-periods analyzed. All isolates were susceptible to micafungin, and most were susceptible to fluconazole, except for C. glabrata. No isolates were resistant to amphotericin B or voriconazole. The overall 30-day mortality was 40.2%. Univariate analysis revealed an association between 30-day mortality and central venous catheter (CVC) removal at any time, high Pitt bacteremia score (PBS), and high Charlson comorbidity index (CCI). Multivariate Cox analysis found that high PBS was the only independent predictor of 30-day mortality; subsequent multivariate Cox regression demonstrated that early CVC removal significantly reduced 30-day mortality. Candida species distribution and antifungal susceptibility profile in our hospital remained similar from 2013 to 2021. Early CVC removal may improve candidemia outcomes.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida glabrata; Candidemia; Candidiasis; Drug Resistance, Fungal; Fluconazole; Hospitals, University; Humans; Japan; Longitudinal Studies; Micafungin; Microbial Sensitivity Tests; Retrospective Studies; Voriconazole

The discovery of amphotericin B, a polyene antifungal compound, in the 1950s, and the formulation of this compound in a liposomal drug delivery system, has resulted in decades of use in systemic fungal infections. The use of liposomal amphotericin B formulation is referenced in many international guidelines for the treatment of fungal infections such as Aspergillus and cryptococcal disease and Candida infections, as well as other less common infections such as visceral leishmaniasis. With the development of liposomal amphotericin B, an improved therapeutic index could be achieved that allowed the attainment of higher drug concentrations in both the plasma and tissue while simultaneously lowering the toxicity compared with amphotericin B deoxycholate. In over 30 years of experience with this drug, a vast amount of information has been collected on preclinical and clinical efficacy against a wide variety of pathogens, as well as evidence on its toxicity. This article explores the history and nature of the liposomal formulation, the key clinical studies that developed the pharmacokinetic, safety and efficacy profile of the liposomal formulation, and the available microbiological data.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Humans; Liposomes; Mycoses

Studies on Candida infections in the central nervous system, especially in infants and young children that did or did not have postoperative surgery, are rarely reported. Thus far, intrathecal (i.t.) amphotericin B (AmB) is not routinely recommended as a therapy for Candida meningitis. We report the first case of Candida meningitis in an infant who underwent abdominal surgery and was successfully treated with i.t. and intravenous (i.v.) AmB in the mainland of China.. Candida meningitis was confirmed by culture and immunoserological tests in a 1-day-old girl after surgery. She was treated with fluconazole for 1 month, but the patient's symptoms showed no improvement.. After surgery, the infant started having recurrent attacks of fever, and laboratory tests of the cerebrospinal fluid (CSF) revealed antigens of Candida tropicalis. CSF tests revealed a high total protein level and a low glucose level. She was diagnosed with a secondary Candida meningitis.. After azole therapy failure, intrathecal and intravenous AmB therapy were used as rescue therapies.. After nearly 2 months of AmB treatment, all repeat CSF cultures were negative, the infant was deemed stable and was discharged home, and she continued taking voriconazole orally as an outpatient.. The combination of i.t. and i.v. administration of AmB can provide a safe and effective alternative to managing this rare but severe disease.

Topics: Administration, Intravenous; Amphotericin B; Antifungal Agents; Candida tropicalis; Candidiasis; China; Digestive System Surgical Procedures; Female; Humans; Infant, Newborn; Injections, Spinal; Meningitis, Fungal; Postoperative Complications

To minimize the intrinsic toxicity of the antibacterial agent hydrazinyloxadiazole 1, the hydrazine moiety was replaced with ethylenediamine (compound 7). This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a conformationally-restricted isostere for ethylenediamine, potentiated the antifungal activity in both the cis and trans forms of N-(5-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)-1,3,4-oxadiazol-2-yl)cyclohexane-1,2-diamine (compounds 16 and 17). Both compounds 16 and 17 were void of any antibacterial activity; nonetheless, they showed equipotent antifungal activity in vitro to that of the most potent approved antifungal agent, amphotericin B. The promising antifungal effects of compounds 16 and 17 were maintained when assessed against an additional panel of 26 yeast and mold clinical isolates, including the Candida auris and C. krusei. Furthermore, compound 17 showed superior activity to amphotericin B in vitro against Candida glabrata and Cryptococcus gattii. Additionally, neither compound inhibited the normal human microbiota, and both possessed excellent safety profiles and were 16 times more tolerable than amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Drug Resistance, Multiple; Fluconazole; Humans; Microbial Sensitivity Tests; Mycoses; Thiazoles

Based on NH

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Cell Survival; Colony Count, Microbial; Female; HEK293 Cells; Hemolysis; Humans; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Sheep; Solubility; Spectrophotometry, Ultraviolet

Independent studies from our group and others have provided evidence that sphingolipids (SLs) influence the antimycotic susceptibility of Candida species. We analyzed the molecular SL signatures of drug-resistant clinical isolates of Candida auris, which have emerged as a global threat over the last decade. This included Indian hospital isolates of C. auris, which were either resistant to fluconazole (FLC

Topics: Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candidiasis; Chromatography, Liquid; Depsipeptides; Drug Resistance, Multiple, Fungal; Fatty Acids, Monounsaturated; Fluconazole; Glucosylceramides; Humans; Lipidomics; Tandem Mass Spectrometry

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Female; Humans

Ravuconazole is an extended-spectrum triazole agent that is efficient in vitro against Candida spp. and has been approved to work as an oral formulae for onychomycosis in Japan in 2018. However, nobody had determined the MIC of ravuconazole against the Candida auris, which is known as an emerging multidrug-resistant yeast. Meanwhile, rare is known of the in vitro activity of ravuconazole against vaginal Candida isolates.. To investigate the activity of ravuconazole against C. auris and vaginal Candida isolates of China and assess the feasibility of ravuconazole in the treatment of candidiasis caused by C. auris and other Candida spp.. We determined the in vitro activity of ravuconazole and 9 comparators against 15 C. auris isolates and determined the MIC of ravuconazole on 525 vaginal Candida isolates (Candida albicans, Candida tropicalis, Candida glabrata and Candida parapsilosis) from 9 provinces of China by Clinical and Laboratory Standards Institute (CLSI) methodology.. The MICs of fluconazole and amphotericin B on C. auris were much higher than second-generation azoles and echinocandins. Ravuconazole was active against all the C. auris isolates and as effective as isavuconazole, posaconazole and echinocandins while showed a better antifungal activity than itraconazole, voriconazole to C. auris. For vaginal Candida isolates, the proportion of ravuconazole-resistant isolates is 0.19% (1/525).. Ravuconazole was in good active against C. auris and vaginal Candida isolates, which suggested ravuconazole could be used in the treatment of drug-resistant candidiasis.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Female; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Thiazoles; Triazoles; Vagina

This study aimed to highlight the association of stellate neuroretinitis occurring secondary to endogenous candidemia.. We report an unusual presentation of endogenous Candida endophthalmitis as a stellate neuroretinitis in the setting of Cornelia de Lange syndrome.. A 34-month-old girl with severe Cornelia de Lange syndrome and a history of parenteral nutrition dependence requiring a chronic central venous catheter presented with bilateral endophthalmitis secondary to candidemia. In one eye, the endophthalmitis had the atypical presentation as a stellate neuroretinitis.. This case represents a unique association of stellate neuroretinitis secondary to Candida infection in a patient with Cornelia de Lange syndrome.

Topics: Administration, Ophthalmic; Amphotericin B; Antifungal Agents; Bacteremia; Candida albicans; Candidemia; Candidiasis; Child, Preschool; De Lange Syndrome; Endophthalmitis; Eye Infections, Fungal; Female; Humans; Intravitreal Injections; Klebsiella; Klebsiella Infections; Retinitis; Voriconazole

Topics: Amphotericin B; Animals; Antifungal Agents; Azoles; Candida glabrata; Candidiasis; Cytokines; Dihydroxyphenylalanine; Drug Resistance, Fungal; Macrophages; Melanins; Mice; Microbial Viability; Virulence

We identified a new series of azole antifungal agents bearing a pyrrolotriazinone scaffold. These compounds exhibited a broad in vitro antifungal activity against pathogenic Candida spp. (fluconazole-susceptible and fluconazole-resistant) and were 10- to 100-fold more active than voriconazole against two Candida albicans isolates with known mechanisms of azole resistance (overexpression of efflux pumps and/or specific point substitutions in the Erg11p/CYP51 enzyme). Our lead compound 12 also displayed promising in vitro antifungal activity against some filamentous fungi such as Aspergillus fumigatus and the zygomycetes Rhizopus oryzae and Mucor circinelloides and an in vivo efficiency against two murine models of lethal systemic infections caused by Candida albicans.

Topics: Animals; Antifungal Agents; Candida albicans; Candidiasis; Drug Resistance, Fungal; Mice; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship; Triazines

Topics: Aged, 80 and over; Amphotericin B; Angiogenesis Inhibitors; Antifungal Agents; Bevacizumab; Candidiasis; Chorioretinitis; Choroidal Neovascularization; Coloring Agents; Drug Therapy, Combination; Eye Infections, Fungal; Fluorescein Angiography; Humans; Indocyanine Green; Intravitreal Injections; Male; Subretinal Fluid; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Visual Acuity

This study evaluated the activity of echinocandins, azoles and amphotericin B against Candida spp. isolates and other yeasts and characterised azole resistance mechanisms in Candida parapsilosis and Candida tropicalis. Invasive Candida spp. isolates (n = 2936) collected in 60 hospitals worldwide during 2016-2017 underwent antifungal susceptibility testing by broth microdilution. Azole-resistant C. parapsilosis and C. tropicalis were submitted to qPCR for ERG11, CDR1 and MDR1, and the whole genome sequence was analysed. Results of non-susceptibility to echinocandins ranged from 0.0-2.3%, being highest in Candida glabrata. More than 99.0% of the Candida albicans isolates were susceptible to both fluconazole and voriconazole. Fluconazole resistance in C. glabrata was 6.5% overall, being highest in the USA (13.0%). Resistance to voriconazole in Candida krusei was only noted in the USA (5.0%). Azoles inhibited 89.1-91.6% of C. parapsilosis isolates, with most resistant isolates noted in Europe (15.1%), including 36 isolates from Italy (three hospitals), of which 34 harboured Erg11 Y132F mutations and overexpressed MDR1. Azole non-wild-type C. tropicalis (7/227) were found in five countries: 3 isolates from Thailand had the same Erg11 Y132F alteration. Fluconazole non-wild-type isolates were noted among 3/77 (3.9%) Candida dubliniensis, 4/17 (23.5%) Candida guilliermondii, 4/47 (8.5%) Candida lusitaniae and other less common yeast species. Echinocandin use has been recommended over fluconazole for invasive Candida infections. However, azoles are still active against the most common Candida spp. and resistance appears to be restricted to certain geographic regions and associated with Erg11 Y132 alterations in C. parapsilosis and C. tropicalis.

Topics: Amino Acid Substitution; Amphotericin B; Antifungal Agents; Azoles; Candida albicans; Candida parapsilosis; Candida tropicalis; Candidiasis; Candidiasis, Invasive; Drug Resistance, Fungal; Echinocandins; Fluconazole; Humans; Microbial Sensitivity Tests; Sterol 14-Demethylase; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Phosphorylcholine

Candida parapsilosis produces biofilm, which colonizes catheters and other invasive medical devices that are manipulated by health care workers. In previous studies, C. parapsilosis in vitro biofilms have exhibited high resistance rates against conventional antifungals, but susceptibility to both echinocandins and lipid formulations of amphotericin B (lipid complex and liposomal). However, a recent study showed good activity of amphotericin B deoxycholate on the biomass of C. parapsilosis biofilms. Although moderate activity of echinocandins has been demonstrated against low metabolic activity biofilms of C. parapsilosis, few studies have analyzed the action of these drugs on high metabolic activity biofilms. Moreover, high biofilm-forming isolates have been associated with central venous catheter-related fungemia outbreaks and higher mortality rates. Therefore, it is relevant to verify the activity of the main antifungal drugs against high metabolic activity biofilms of C. parapsilosis. Our study aimed to evaluate the in vitro activity of amphotericin B deoxycholate, anidulafungin, caspofungin, and micafungin against high biofilm-forming and high metabolic activity clinical isolates of C. parapsilosis. Our results showed good activity of amphotericin B against C. parapsilosis biofilms, but none of the echinocandin drugs was effective. This suggests that amphotericin B deoxycholate may be a better choice than echinocandins for the treatment of biofilm-associated infections by C. parapsilosis, mainly in countries with insufficient health care resources to purchase lipid formulations of amphotericin B. These results warn of the possibility of persistent catheter-related candidemia caused by high biofilm-forming C. parapsilosis strains when treated with echinocandin drugs.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida parapsilosis; Candidemia; Candidiasis; Catheter-Related Infections; Deoxycholic Acid; Drug Combinations; Drug Evaluation, Preclinical; Echinocandins; Humans; Microbial Sensitivity Tests

Bloodstream Candida infection is a life-threatening event among ICU admitted patients. This infection is caused by a diverse range of Candida species having varied minimum inhibitory concentrations.. To identify Candida species causing bloodstream infections with their antifungal susceptibility determination.. Candida species isolated from the blood of ICU admitted patients were identified by phenotypic as well as by molecular methods including PCR-RFLP using MspI restriction enzyme and MALDI TOF MS. The minimum inhibitory concentration of fluconazole, voriconazole, amphotericin B and caspofungin was determined against isolated Candida species by CLSI M27A. A total of 119 Candida species were isolated. Among them, C. tropicalis(n=29) was the predominant isolate followed by C. parapsilosis(n=18), C. glabrata (n=12), C. krusei (n=11) and C. albicans(n=11). Uncommon Candida species isolated were; Wickerhamomyces anomalus(n=15), Kodaemia ohmeri(n=8), C. lusitaniae (n=5) and C. auris (n=2). A varied antifungal MIC values were observed. Caspofungin had the lowest MIC among the tested antifungals. Increased fluconazole MIC was observed against the isolated Candida species including C. tropicalis. All the isolated C. lusitaniae and C. auris strains have ≥1mcg/ml amphotericin B MIC. In comparison to fluconazole, voriconazole was more effective when tested in vitro.. Emergence of uncommon Candida species having varied antifungal MIC warns the physicians to have a prompt, accurate identification with antifungal MIC determination in each case of bloodstream Candida infections.

Topics: Amphotericin B; Antifungal Agents; Bacteremia; Candida; Candida tropicalis; Candidiasis; Caspofungin; Cross-Sectional Studies; Fluconazole; Humans; Intensive Care Units; Microbial Sensitivity Tests; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Voriconazole

Candida krusei is one of the most common agents of invasive candidiasis and candidemia worldwide, leading to high morbidity and mortality rates. This species has become a problem due to its intrinsic resistance and reduced susceptibility to azoles and polyenes. Moreover, the number of antifungal drugs available for candidiasis treatment is limited, demonstrating the urgent need for the discovery of novel alternative therapies. In this work, the in vivo and in vitro activities of a new oxadiazole (LMM11) were evaluated against C. krusei. The minimum inhibitory concentration ranged from 32 to 64 μg/mL with a significant reduction in the colony forming unit (CFU) count (~3 log10). LMM11 showed fungicidal effect, similar to amphotericin, reducing the viable cell number (>99.9%) in the time-kill curve. Yeast cells presented morphological alterations and inactive metabolism when treated with LMM11. This compound was also effective in decreasing C. krusei replication inside and outside macrophages. A synergistic effect between fluconazole and LMM11 was observed. In vivo treatment with the new oxadiazole led to a significant reduction in CFU (0.85 log10). Furthermore, histopathological analysis of the treated group exhibited a reduction in the inflammatory area. Taken together, these results indicate that LMM11 is a promising candidate for the development of a new antifungal agent for the treatment of infections caused by resistant Candida species such as C. krusei.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cell Survival; Humans; Macrophages; Oxadiazoles; Stem Cells

Amphotericin B (AmB) is the antifungal with the strongest fungicidal activity, but its use has several limitations, mainly associated with its toxicity. Although some lipidic and liposomal formulations that present reduced toxicity are available, their price limits their application in developing countries. Flucytosine (5FC) has shown synergistic effect with AmB for treatment of some fungal infections, such as cryptococcosis, but again, its price is a limitation for its use in many regions. In the present work, we aimed to identify new drugs that have a minor effect on

Topics: Amphotericin B; Animals; Antifungal Agents; Auranofin; Candida albicans; Candidiasis; Cell Line; Ciclopirox; Cryptococcosis; Cryptococcus neoformans; Drug Evaluation, Preclinical; Drug Repositioning; Drug Synergism; Erythromycin; Flucytosine; Humans; Mice; Microbial Sensitivity Tests; Opportunistic Infections; RAW 264.7 Cells; Zebrafish

Hydrogels from Halomonas levan polysaccharide were prepared at different crosslinking densities. Swelling results demonstrated pH dependent rather than temperature dependent swelling of the hydrogel and the highest swelling value was achieved at basic conditions with a swelling ratio of 9.1 ± 0.1 which is the highest reported for levan based hydrogels. SEM images show a porous network architecture, which indicates a large surface area of the hydrogels. Rheological analyses showed the viscoelastic behavior of the hydrogels. Biocompatibility of the hydrogels was confirmed by cell culture experiments. For drug release experiments Amphotericin B (AmB) was used. 51% of the loaded AmB was released into the PBS buffer and the released AmB had a significant antifungal activity against Candida albicans.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Cell Line; Delayed-Action Preparations; Drug Liberation; Fructans; Hydrogels; Mice

To evaluate the optical coherence tomography (OCT) features of retinal lesions in Chinese patients with endogenous Candida endophthalmitis (ECE).. We performed a retrospective review of patients diagnosed with ECE at one medical center. The medical records of the patients including predisposing risk factors, treatment and visual acuity were reviewed. And we focused on the analysis of OCT images of retinal lesions before and after treatment.. A total of 16 Chinese patients (22 eyes) were included in this study. The most frequent predisposing risk factors were intravenous use of corticosteroids or antibiotics, lithotripsy for urinary calculi, and diabetes. After treatment, visual acuity was improved in 13 (59.1%) of the 22 eyes, and remained the same in the other 9 (40.9%) eyes. Pre-treatment OCT images obtained at presentation were available for 17 of the 22 eyes. Four types of the OCT manifestations of retinal lesions were identified: type 1 (subretinal macular lesions), type 2 (lesions are located in the inner retinal layer), type 3 (lesions involve the full-thickness retina and accompanied with macular edema), type 4 (sub-inner limiting membrane lesions). Pre-treatment OCT imaging of the 17 eyes revealed five as type 1, four as type 2, six as type 3, and two as type 4. After treatment, OCT images revealed epiretinal membrane and subretinal fibrosis as the most common post-treatment complications of ECE. Epiretinal membrane was detected in 2/4 type 2 lesions, in 4/6 type 3 lesions, and in 1/2 type 4 lesions, while subretinal fibrosis was mainly seen in type 1 lesions (4/5). Among the types, visual prognosis was best in eyes with type 2 lesions.. In this case series, the OCT manifestations of retinal lesions in ECE could be classified into four types. The post-treatment OCT manifestations were different in four types of lesions. We preliminarily found that the OCT morphology of retinal lesions was associated with the visual prognosis of ECE.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Asian People; Candidiasis; Endophthalmitis; Eye Infections, Fungal; Female; Fluorescein Angiography; Humans; Intravitreal Injections; Male; Middle Aged; Retinal Diseases; Retrospective Studies; Tomography, Optical Coherence; Visual Acuity; Vitrectomy; Young Adult

Topics: Acetaminophen; Acidosis; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Antipyretics; Candida; Candidiasis; Child; Febrile Neutropenia; Humans; Leukemia, Myeloid, Acute; Male; Pyrrolidonecarboxylic Acid

Biofilm formation poses an important clinical trouble due to resistance to antimicrobial agents; therefore, there is an urgent demand for new antibiofilm strategies that focus on the use of alternative compounds also in combination with conventional drugs. Drug-tolerant persisters are present in Candida albicans biofilms and are detected following treatment with high doses of amphotericin B. In this study, persisters were found in biofilms treated with amphotericin B of two clinical isolate strains, and were capable to form a new biofilm in situ. We investigated the possibility of eradicating persister-derived biofilms from these two Candida albicans strains, using the peptide gH625 analogue (gH625-M). Confocal microscopy studies allowed us to characterize the persister-derived biofilm and understand the mechanism of interaction of gH625-M with the biofilm. These findings confirm that persisters may be responsible for Candida biofilm survival, and prove that gH625-M was very effective in eradicating persister-derived biofilms both alone and in combination with conventional antifungals, mainly strengthening the antibiofilm activity of fluconazole and 5-flucytosine. Our strategy advances our insights into the development of effective antibiofilm therapeutic approaches.

Topics: Amino Acid Sequence; Amphotericin B; Antifungal Agents; Antimicrobial Cationic Peptides; Biofilms; Candida albicans; Candidiasis; Drug Design; Drug Resistance, Fungal; Humans

Candida albicans is a commensal yeast able to cause life threatening invasive infections particularly in immunocompromised patients. Despite the availability of antifungal treatments, mortality rates are still unacceptably high and drug resistance is increasing. We, therefore, generated the Ca37 monoclonal antibody against the C. albicans alcohol dehydrogenase (Adh) 1. Our data showed that Ca37 was able to detect C. albicans cells, and it bound to Adh1 in yeast and Adh2 in hyphae among the cell wall-associated proteins. Moreover, Ca37 was able to inhibit candidal growth following 18 h incubation time and reduced the minimal inhibitory concentration of amphotericin B or fluconazole when used in combination with those antifungals. In addition, the antibody prolonged the survival of C. albicans infected-Galleria mellonella larvae, when C. albicans was exposed to antibody prior to inoculating G. mellonella or by direct application as a therapeutic agent on infected larvae. In conclusion, the Ca37 monoclonal antibody proved to be effective against C. albicans, both in vitro and in vivo, and to act together with antifungal drugs, suggesting Adh proteins could be interesting therapeutic targets against this pathogen.

Topics: Alcohol Dehydrogenase; Amphotericin B; Animals; Antibodies, Monoclonal; Antifungal Agents; Candida albicans; Candidiasis; Fluconazole; Fungal Proteins; Hyphae; Larva; Microbial Sensitivity Tests; Moths; Virulence

Candida sp. osteoarticular infection is rare and most often due to hematogenous seeding during an episode of candidemia in immunocompromised patients. However, the diagnosis can be delayed in patients with subtle symptoms and signs of joint infection without a concurrent episode of candidemia.. A 75-year-old woman presented with a three-year history of pain and swelling of the left knee. Candida pelliculosa was detected from the intraoperative tissue when the patient had undergone left total knee arthroplasty 32 months ago, but no antifungal treatment was performed. One year after the total knee arthroplasty, C. pelliculosa was repeatedly isolated from the left knee synovial fluid and antifungal treatment comprising amphotericin B deoxycholate and fluconazole was administered. However, joint infection had extended to the adjacent bone and led to progressive joint destruction. The patient underwent surgery for prosthesis removal and received prolonged antifungal treatment with micafungin and fluconazole.. This case shows that C. pelliculosa, an extremely rare non-Candida albicans sp., can cause fungal arthritis and lead to irreversible joint destruction owing to delayed diagnosis and treatment.

Topics: Aged; Amphotericin B; Antifungal Agents; Arthritis, Infectious; Arthroplasty, Replacement, Knee; Candida; Candidemia; Candidiasis; Deoxycholic Acid; Device Removal; Drug Combinations; Female; Fluconazole; Humans; Intraoperative Care; Joint Prosthesis; Knee; Micafungin; Osteomyelitis

Candida albicans is a major cause of human infections, ranging from relatively simple to treat skin and mucosal diseases to systemic life-threatening invasive candidiasis. Fungal infections treatment faces three major challenges: the limited number of therapeutic options, the toxicity of the available drugs, and the rise of antifungal resistance. In this study, we demonstrate the antifungal activity and mechanism of action of peptides ToAP2 and NDBP-5.7 against planktonic cells and biofilms of C. albicans. Both peptides were active against C. albicans cells; however, ToAP2 was more active and produced more pronounced effects on fungal cells. Both peptides affected C. albicans membrane permeability and produced changes in fungal cell morphology, such as deformations in the cell wall and disruption of ultracellular organization. Both peptides showed synergism with amphotericin B, while ToAP2 also presents a synergic effect with fluconazole. Besides, ToAP2 (6.25 µM.) was able to inhibit filamentation after 24 h of treatment and was active against both the early phase and mature biofilms of C. albicans. Finally, ToAP2 was protective in a Galleria mellonella model of infection. Altogether these results point to the therapeutic potential of ToAP2 and other antimicrobial peptides in the development of new therapies for C. albicans infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Cell Membrane Permeability; Cell Wall; Disease Models, Animal; Drug Resistance, Fungal; Drug Synergism; Drug Therapy, Combination; Fluconazole; Humans; Microbial Sensitivity Tests; Moths; Pore Forming Cytotoxic Proteins

Two fungal endophthalmitis cases demonstrate safety and efficiency of intravitreal caspofungin as a new therapy option in fungal endophthalmitis.. The purpose of this study was to evaluate the intravitreal application of caspofungin for the treatment of fungal endophthalmitis because rising resistance to voriconazole and amphotericin B leads to a need for new antifungal therapy options.. Initially, both patients with fungal endophthalmitis underwent pars plana vitrectomy. Microbiological analysis revealed Aspergillus terreus and Candida dubliniensis, which both possess atypical resistance patterns. Caspofungin has a low bioavailability in the eye when given systemically. It was injected intravitreally into the eyes affected by fungal endophthalmitis. An injection of 100 μg of caspofungin in a volume 0.1 mL was applied repeatedly. Clinical parameters were recorded. Both eyes were stabilized by the treatment. Finally, the intraocular infections with atypical mycotic agents were eliminated. Visual acuity improved to 0.4 logMAR (20/50 Snellen) in the first case and to 1.0 logMAR (20/200 Snellen) in the second case. During the treatment course, we have not seen any toxic effects or damage of intraocular structures related to the intravitreal administration of caspofungin.. In summary, intravitreal caspofungin was effective and well tolerated in both cases. Therefore, caspofungin seems to be a safe and effective intravitreal alternative to voriconazole and amphotericin B in fungal endophthalmitis.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Blood-Retinal Barrier; Candida; Candidiasis; Caspofungin; Endophthalmitis; Eye Infections, Fungal; Humans; Intravitreal Injections; Male; Visual Acuity; Vitrectomy; Voriconazole

To determine the concentration of amphotericin B that would be both effective against Candida albicans contamination and safe for corneal endothelial cells (CECs) in cold storage conditions.. Triplicate media cultures were inoculated with 10 colony-forming units (CFUs)/mL of C. albicans (American Type Culture Collection 10231), supplemented with amphotericin B (0-20 μg/mL), stored in cold conditions (2°C-8°C) for 72 hours, and analyzed quantitatively for CFUs. C. albicans concentration in each sample was determined initially and after 6, 24, 48, and 72 hours of storage. CEC mitochondrial function (oxygen consumption rate), apoptosis, and necrosis were examined in donor corneas after 7 days of amphotericin B exposure and compared with untreated controls. CEC viability was also examined by calcein-AM staining and Fiji segmentation after 72 hours or 2 weeks of amphotericin B exposure to mimic potential eye bank practices.. Amphotericin B concentrations of 1.25, 2.5, and 5.0 μg/mL resulted in 0.47, 1.11, and 1.21 log10 CFU reduction after only 6 hours of cold storage and continued to decrease to 3.50, 3.86, and 4.49 log10 reductions after 72 hours, respectively. By contrast, amphotericin B 0.255 µg/mL showed only 1.01 log10 CFU reduction after 72 hours of incubation. CEC mitochondrial function and viability did not differ in donor corneas exposed to amphotericin B ≤2.59 μg/mL compared with the controls.. Optimal efficacy of amphotericin B against C. albicans is achieved in cold storage conditions at concentrations ≥1.25 μg/mL, and 2.5 μg/mL reduces Candida contamination by >90% after 6 hours of cold storage without sacrificing CEC health.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Dose-Response Relationship, Drug; Endothelium, Corneal; Eye Banks; Eye Infections, Fungal; Humans; Keratitis; Microbial Sensitivity Tests; Organ Preservation; Surgical Wound Infection

The increase of opportunistic fungal infections raises the need for design and synthesis of new antifungal agents. Taking into account that tetrazole derivatives exhibit antifungal activity, and some of them are in the phase of clinical trials, new tetrazole derivatives bearing pyrrolidine moiety were synthesized in order to present their action mode against C. albicans. The target compounds were obtained by N-alkylation of various 2-arylpyrrolidines with several 1-(3-chloropropyl)-5-aryl-2H-tetrazoles. Regardless of the substituents at tetrazole or pyrrolidine rings reactions took place in 48 h and with satisfactory yields ranging from 53 to 70%. We performed screen of the synthesized compounds to identify these nontoxic inhibiting the C. albicans planktonic and sessile cells, and conducted a series of follow up studies to examine the in vitro and in vivo activity of the most potent antifungals. The leading antifungal inhibitor: 2-{3-[2-(3-Methylphenyl)pyrrolidin-1-yl]propyl}-5-phenyl-2H-tetrazole (3aC) and the randomly selected ones: 5-phenyl-2-[3-(2-phenylpyrrolidin-1-yl)propyl]-2H-tetrazole (3aA), 5-(4-chlorophenyl)-2-{3-[2-(4-fluorophenyl)pyrrolidin-1-yl]propyl}-2H-tetrazole (3cD), and 5-(4-chlorophenyl)-2-{3-[2-(4-chlorophenyl)pyrrolidin-1-yl]propyl}-2H-tetrazole (3cE) showed little to no toxicity against the Vero cell line and Galleria mellonella. 3aC and 3aD, the most active against biofilm in vitro, demonstrated in vivo activity in the invertebrate model of disseminated candidiasis. Flow cytometry analysis showed that necrotic cell death was generated under 3aC due to its interactions with the fungal membrane; this confirmed by the mitochondrial damage (XTT assay) and reduced adhesion to the TR-146 cell line at 46.05 μM. Flow cytometry was used to directly measure the redox state of the treated cells with the fluorescent DCFH probe. Pro-necrotic tetrazole derivatives (3aA, 3aC, 3cD) are unable to induce ROS production in the C. albicans cells. Moreover, CLSM analyses revealed that the tetrazole derivatives (principally 3aC, 3aD, and 3aE) inhibit C. albicans' ability to neutralize macrophages; a more effective phagosomes organisation was observed. 3aC's and 3aD's activity reflected in an attenuation of virulence in disseminated candidiasis in vivo.

Topics: Alkylation; Animals; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Cell Line; Chlorocebus aethiops; Necrosis; Pyrrolidines; Structure-Activity Relationship; Tetrazoles; Virulence

Candida albicans frequently causes variety of superficial and invasive disseminated infections in HIV infected patients. Further, the emergence of non albicans species causing candidiasis predominantly in patients with advanced immune-suppression and drug resistance brings great apprehension. Hence, in this study we evaluate the capability of eugenol (EUG), a natural compound in combination with less toxic concentrations of amphotericin B (AmpB) for enhanced antifungal effects and reduced toxicity. Antifungal activity and time-kill assay were employed according to Clinical Laboratory Standard Institute (CLSI) guidelines with minor modifications on clinical isolates of Candida albicans. To confirm the synergistic interaction of EUG and AmpB, checkerboard experiments were employed. Interestingly, EUG-Amp B combination shows many fold higher anti-candida activity compared to single component treatment. Furthermore, our results depicts reactive oxygen species (ROS) driven killing and mitochondrial hyperpolarisation on treatment. Our data also suggests inhibition of calcium channel by EUG and predicts longer retainment of AmpB. Pronounced cellular damage was observed with combination treatment than to EUG and AmpB alone. Our finding is helpful for the removal of toxic concentrations of antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Calcium Channels; Candida albicans; Candidiasis; Drug Synergism; Eugenol; Fungal Proteins; Humans; Models, Molecular; Reactive Oxygen Species

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Eye; Humans; Intravitreal Injections; Magnetic Resonance Imaging; Male; Panophthalmitis; Tomography, X-Ray Computed; Vision Disorders

Topical application of poorly water-soluble antibiotics cannot achieve the desired therapeutic concentration within cornea. The purpose of this study was to fabricate, characterize and evaluate in-vivo effectiveness of amphotericin B (AmB) containing microneedle ocular patch (MOP) against fungal keratitis. MOP containing free or liposomal AmB was fabricated using micromolding technique to mimic contact lens. MOPs were prepared using dissolvable polymeric matrix including polyvinyl alcohol and polyvinyl pyrrolidone. AmB loaded MOP were studied for their physical and mechanical properties, drug loading and dissolution rate, corneal insertion and drug permeability. MOP loaded with 100 µg AmB had a compression strength of 35.1 ± 6.7 N and required an insertional force of 1.07 ± 0.17 N in excised human cornea. Ex-vivo corneal permeation studies revealed significant enhancement in AmB corneal retention with the application of MOP compared with free AmB or liposomal AmB application. Furthermore, AmB loaded MOP application significantly (P < 0.05) reduced the Candida albicans load within cornea as evaluated in both ex-vivo model and in-vivo rabbit infection model. Histological examination showed that AmB MOP treatment improved the epithelial and stromal differentiation of corneal membrane. AmB containing MOPs can be developed as minimally invasive corneal delivery device for effective treatment of fungal keratitis.

Topics: Administration, Ophthalmic; Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Compressive Strength; Disease Models, Animal; Dosage Forms; Drug Compounding; Drug Delivery Systems; Eye Infections, Fungal; Humans; Keratitis; Male; Miniaturization; Needles; Permeability; Phosphatidylcholines; Polyvinyl Alcohol; Povidone; Rabbits

Oral candidiasis as a highly prevalent and recurrent infection in medically compromised individuals is mainly caused by the opportunistic fungal pathogen

Topics: Amphotericin B; Antifungal Agents; Biofilms; Biological Availability; Candida albicans; Candidiasis; Carbon; Epithelial Cells; Guanosine Monophosphate; Humans; Invasive Fungal Infections; Keratinocytes; Microbial Sensitivity Tests; Mouth Mucosa; Polyenes; Quantum Dots

Amphotericin B is an antibiotic used as the "gold standard" in the treatment of life-threatening fungal infections. Several molecular mechanisms have been proposed to explain exceptionally high effectiveness of amphotericin B in combating fungi. In the present work, we apply fluorescence lifetime imaging microscopy to track, step by step, modes of the toxic activity of amphotericin B towards a clinical strain of Candida albicans. The images recorded reveal that the antibiotic binds to cells in the form of the small aggregates characterized by a relatively short fluorescence lifetime (0.2 ns). Amphotericin B binds preferentially to the cell walls of mature cells but also to the plasma membranes of the daughter cells at the budding stage. The images recorded with the application of a scanning electron microscopy show that the antibiotic interferes with the formation of functional cell walls of such young cells. The results of imaging reveal the formation of the amphotericin B-rich extramembranous structures and also binding of the drug molecules into the cell membranes and penetration into the cells. These two modes of action of amphotericin B are observed in the time scale of minutes.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Cell Membrane; Cell Wall; Humans; Microbial Sensitivity Tests; Microscopy, Fluorescence

Combination therapies can be a help to overcome resistance to current antifungals in humans. The combined activity of commercial antifungals and soluble and well-defined low molecular weight chitosan with average degrees of polymerization (DPn) of 17-62 (abbreviated C17 -C62) and fraction of acetylation (FA) of 0.15 against medically relevant yeast strains was studied. The minimal inhibitory concentration (MIC) of C32 varied greatly among strains, ranging from > 5000 μg mL-1 (Candida albicans and C. glabrata) to < 4.9 (C. tropicalis). A synergistic effect was observed between C32 and the different antifungals tested for most of the strains. Testing of several CHOS preparations indicated that the highest synergistic effects are obtained for fractions with a DPn in the 30-50 range. Pre-exposure to C32 enhanced the antifungal effect of fluconazole and amphotericin B. A concentration-dependent post-antifungal effect conserved even 24 h after C32 removal was observed. The combination of C32 and commercial antifungals together or as part of a sequential therapy opens new therapeutic perspectives for treating yeast infections in humans.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Chitosan; Drug Resistance, Fungal; Drug Synergism; Drug Therapy, Combination; Fluconazole; Humans; Microbial Sensitivity Tests; Polymerization; Proton Magnetic Resonance Spectroscopy

Chest fungal infection is a rarely seen lethal disease with rapid progression. Sufficient residence time of antifungal agent with therapeutic concentration in the chest is an essential point during anti-infection therapy, which is hard to achieve via conventional systemic drug delivery. We here by describe a case of successful treatment of fungal Chest infection via local pleural lavage. A 59 years old male was hospitalized due to chest pain. X-ray of chest and bacterial culture of thoracic drainage fluid and blood indicated severe chest infection of Candida albicans. The patient was initially administered intravenously with amphotericin B (25mg/day). However, the symptoms were not significantly improved after 5 days of treatment. Then one-hour pleural lavage of 5mg amphotericin B in volume of 50ml 5% glucose solution was added once daily. On day 12, bacterial cultures showed negative, and chest X-ray exhibited apparent decrease of shadow area, also other examinations such as body temperature and white blood cell count suggested significant improvement of infection. The therapeutic strategy of amphotericin B was maintained until two consecutive bacterial cultures were negative, then was switched back to intravenous drip alone for another one month found. No significant adverse effects were observed during the treatment. In conclusion, this case demonstrates a new local pleural lavage method of amphotericin B for chest fungal infection, which may provide a reference for the treatment of such cases.

Topics: Amphotericin B; Antifungal Agents; Bronchoalveolar Lavage; Candida albicans; Candidiasis; Empyema, Pleural; Humans; Male; Middle Aged

Candida auris is a multidrug-resistant yeast associated with hospital outbreaks worldwide. During 2015-2016, multiple outbreaks were reported in Colombia. We aimed to understand the extent of contamination in healthcare settings and to characterize the molecular epidemiology of C. auris in Colombia.. We sampled patients, patient contacts, healthcare workers, and the environment in 4 hospitals with recent C. auris outbreaks. Using standardized protocols, people were swabbed at different body sites. Patient and procedure rooms were sectioned into 4 zones and surfaces were swabbed. We performed whole-genome sequencing (WGS) and antifungal susceptibility testing (AFST) on all isolates.. Seven of the 17 (41%) people swabbed were found to be colonized. Candida auris was isolated from 37 of 322 (11%) environmental samples. These were collected from a variety of items in all 4 zones. WGS and AFST revealed that although isolates were similar throughout the country, isolates from the northern region were genetically distinct and more resistant to amphotericin B (AmB) than the isolates from central Colombia. Four novel nonsynonymous mutations were found to be significantly associated with AmB resistance.. Our results show that extensive C. auris contamination can occur and highlight the importance of adherence to appropriate infection control practices and disinfection strategies. Observed genetic diversity supports healthcare transmission and a recent expansion of C. auris within Colombia with divergent AmB susceptibility.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Carrier State; Colombia; Drug Resistance, Fungal; Environmental Microbiology; Humans; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Typing; Mycological Typing Techniques; Whole Genome Sequencing

Fungal central nervous system (CNS) infections show a high mortality rate and only a few antifungal agents are available to treat these infections. We hypothesize that the different biochemical properties of human cerebrospinal fluid (CSF) compared to the standard growth medium lead to the altered activity of antifungal agents in CSF. We investigated the in vitro activity of two of these agents, i.e., amphotericin B (AmB) and voriconazole (VOR), against three different fungi in CSF in comparison to sabouraud-dextrose broth (SDB).. CSF samples from patients who did not receive any antibiotics were collected. Time-kill curves were performed in CSF and SDB using static antibiotic concentrations of AmB and VOR against ATCC strains of Candida albicans, Candida krusei, and Cryptococcus neoformans.. In our experiments, both AmB and VOR showed superior activity in SDB compared to CSF. Nevertheless, AmB achieved fungicidal activity in CSF after 24 h against all test strains. Voriconazole only achieved fungistatic activity against C. albicans and C. neoformans in CSF.. In summary, our data demonstrate that growth of fungal pathogens but even more importantly activity of antifungal agents against Candida and Cryptococcus species can differ significantly in CSF compared to the standard growth medium. Both findings should be taken into consideration when applying PK/PD simulations to fungal infections of the CNS.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candidiasis; Central Nervous System Infections; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Humans; Voriconazole

The aims of this study were as follows. First, we sought to compare the in vitro susceptibility of liposomal amphotericin B (LAmB) and anidulafungin on Candida albicans and Candida glabrata biofilms growing on silicone discs. Second, we sought to compare the activity of LAmB versus anidulafungin for the treatment of experimental catheter-related C. albicans and C. glabrata infections with the antifungal lock technique in a rabbit model.. Two C. albicans and two C. glabrata clinical strains were used. The minimum biofilm eradication concentration for 90% eradication (MBEC90) values were determined after 48h of treatment with LAmB and anidulafungin. Confocal microscopy was used to visualize the morphology and viability of yeasts growing in biofilms. Central venous catheters were inserted into New Zealand rabbits, which were inoculated of each strain of C. albicans and C. glabrata. Then, catheters were treated for 48h with saline or with antifungal lock technique using either LAmB (5mg/mL) or anidulafungin (3.33mg/mL).. In vitro: anidulafungin showed greater activity than LAmB against C. albicans and C. glabrata strains. For C. albicans: MBEC90 of anidulafungin versus LAmB: CA176, 0.03 vs. 128 mg/L; CA180, 0.5 vs. 64 mg/L. For C. glabrata: MBEC90 of anidulafungin versus LAmB: CG171, 0.5 vs. 64 mg/L; CG334, 2 vs. 32 mg/L. In vivo: for C. albicans species, LAmB and anidulafungin achieved significant reductions relative to growth control of log10 cfu recovered from the catheter tips (CA176: 3.6±0.3 log10 CFU, p≤0.0001; CA180: 3.8±0.1 log10 CFU, p≤0.01). For C. glabrata, anidulafungin lock therapy achieved significant reductions relative to the other treatments (CG171: 4.8 log10 CFU, p≤0.0001; CG334: 5.1 log10 CFU, p≤0.0001).. For the C. albicans strains, both LAmB and anidulafungin may be promising antifungal lock technique for long-term catheter-related infections; however, anidulafungin showed significantly higher activity than LAmB against the C. glabrata strains.

Topics: Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Biofilms; Candida; Candida albicans; Candida glabrata; Candidiasis; Catheter-Related Infections; Catheters; Models, Theoretical; Rabbits

Opportunistic infections frequently develop in immunocompromised patients, such as those with hematological malignancies, causing significant mortality. Early diagnosis of invasive fungal infections is often important and difficult due to the difficult nature of confirming infection using cytologic and histologic findings. However, we report the first case of candidal infection leading to muscle abscesses in the legs of a patient with leukemia.. A 60-year-old man with acute myeloid leukemia (AML) presented with multifocal muscle abscesses of the legs.. Multifocal muscle candidiasis of the legs was confirmed by fine-needle aspiration biopsy of 2 of the calf lesions.. After treatment with amphotericin B and flucytosine for 1 month, the patient was administered intravenous caspofungin for 3 months.. A CT scan of the abdomen and an MRI of the lower calves showed significant improvement.. This case highlights that fungal infection should be considered when patients present with multiple abscesses, emphasizing the value of early biopsy to confirm diagnosis and facilitate precision treatment.

Topics: Abscess; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Candida tropicalis; Candidiasis; Caspofungin; Flucytosine; Humans; Immunocompromised Host; Leg; Leukemia, Myeloid, Acute; Magnetic Resonance Imaging; Male; Middle Aged; Muscle, Skeletal; Muscular Diseases; Opportunistic Infections; Tomography, X-Ray Computed

Fungal infections in lamellar keratoplasty are a growing concern. Optisol-GS does not contain an antifungal agent and supplementation with 0.255 μg/mL Amphotericin B (AmpB) has been considered. This study tested the ability of 0.255 μg/mL AmpB in Optisol-GS to eliminate yeast contamination of corneal tissue.. Three isolates of Candida albicans, 1 of Candida parapsilosis, and 1 of Candida glabrata were tested in Optisol with and without AmpB. Corneoscleral rims stored at -80°C were thawed and placed in 10 multiwell plates (4 per plate). The rims were inoculated with 4 respective loads of yeast: 0, 10, 10, and 10 colony-forming units in 2 sets of 5 for 5 yeasts. One set was filled with Optisol plus AmpB and the other with Optisol only. All 10 plates were incubated at cold storage (2°C-8°C) for 48 hours. After 48 hours, all corneal rims were placed into 10 mL of yeast extract peptone dextrose medium; a swab culture of each well was plated onto Sabouraud plates; and all plates with the remaining Optisol were incubated at 30°C. Yeast growth was monitored for 10 days. Minimum inhibitory concentration and minimum fungicidal concentration were determined.. All corneoscleral specimens were positive regardless of fungal load or presence of AmpB. All controls remained negative. Minimum inhibitory concentrations and minimum fungicidal concentrations were equivalent and ranged between 0.5 and 2.0 μg/mL.. AmpB at a concentration of 0.255 μg/mL in Optisol-GS at cold storage (2°C-8°C) over 48 hours did not eliminate yeast from corneal tissue.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Chondroitin Sulfates; Complex Mixtures; Cornea; Dextrans; Eye Banks; Eye Infections, Fungal; Gentamicins; Humans; Organ Preservation; Organ Preservation Solutions

The sexual cycle of Candida glabrata is not known; however, genomic evidence is indicative of recombination among subpopulations and the genome harbours genes necessary for undergoing mating and meiosis, which may increase fitness. The relationship between specific mating type-like (MTL) loci and antifungal susceptibility is not well understood in C. glabrata. We investigated different combinations of clinical C. glabrata isolate mating types and their antifungal susceptibility profiles. Allele profiles of the mating genes of 103 clinical C. glabrata isolates were identified, and their antifungal susceptibility to azoles, echinocandins and amphotericin B were compared. The majority (88.3%) of screened isolates harboured the a allele in the locus. The MTL1, MTL2 and MTL3 loci harboured a (88.3%), a (95.1%), and α (71.8%) alleles, respectively. The C. glabrata isolates were susceptible to echinocandins but displayed high minimal inhibitory concentrations (MICs) for azoles. The MIC ranges and MIC90 values of all isolates were 1.0 to ≥64 and 8.0 μg mL

Topics: Alleles; Amphotericin B; Antifungal Agents; Azoles; Candida glabrata; Candidiasis; Drug Resistance, Multiple, Fungal; Echinocandins; Genes, Mating Type, Fungal; Genotype; Humans; Microbial Sensitivity Tests; Turkey

Due to the antibacterial resistance crisis, developing new antibacterials is of particular interest. In this study, we combined the antifungal drug amphotericin B with 50,520 different small molecule compounds obtained from the Chinese National Compound Library in an attempt to improve its efficacy against Candida albicans persister cells. To systematically study the antifungal effect of each compound, we utilized custom-designed high-throughput microfluidic chips. Our microfluidic chips contained microchannels ranging from 3 µm to 5 µm in width to allow Candida albicans cells to line up one-by-one to facilitate fluorescence-microscope viewing. After screening, we were left with 10 small molecule compounds that improved the antifungal effects of amphotericin B more than 30% against Candida albicans persister cells.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Drug Evaluation, Preclinical; Drug Resistance, Fungal; Drug Synergism; Fungal Proteins; High-Throughput Screening Assays; Humans; Lab-On-A-Chip Devices; Microbial Sensitivity Tests; Microfluidic Analytical Techniques

A 78-year-old woman with a long-term ankle spacer with antibacterials developed an intra-articular

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cartilage, Articular; Caspofungin; Drug Therapy, Combination; Female; Fluconazole; Humans

Candida albicans causes a high mortality rate in immunocompromised individuals, but the increased drug resistance challenges the current antifungal therapeutics. Fluphenazine (FPZ), a commonly used antipsychotic medication, can induce the expression of drug efflux pumps in C. albicans and, thus, may interfere with the therapeutic efficacy of antifungals, such as fluconazole (FLC) and amphotericin B (AmB). Here, we investigated the combined effects of FLC/FPZ and AmB/FPZ against C. albicans in vitro and in a systemic candidiasis mouse model. The antifungal activity of FLC was significantly reduced when supplemented with FPZ. The inhibitory effects of FLC on the expression of the Candida virulence-related genes ALS3 and HWP1 were antagonized by FPZ. However, FPZ enhanced the susceptibility of C. albicans to AmB and further downregulated the expression of ALS3 and HWP1 in a synergistic manner with AmB. FPZ also enhanced the gene expression of ERG11, a key gene of the ergosterol biosynthesis pathway that has been associated with the activities of both FLC and AmB. In our mammalian infection model, mice treated with FLC/FPZ showed notably poor living status and increased fungal burden in their kidneys and brains compared with those treated with FLC alone. Conversely, the combined application of AmB/FPZ significantly improved the survival rate, attenuated the weight loss and reduced the organ fungal burdens of the infected mice. These data suggest that FPZ antagonized the therapeutic efficacy of FLC but enhanced the antifungal activity of AmB in the treatment of candidiasis.

Topics: Amphotericin B; Animal Structures; Animals; Antifungal Agents; Antipsychotic Agents; Candida albicans; Candidiasis; Colony Count, Microbial; Disease Models, Animal; Drug Interactions; Fluconazole; Fluphenazine; Gene Expression Profiling; Gene Expression Regulation, Fungal; Mice; Treatment Outcome

To evaluate a new corneal cold storage medium including an antimycotic tablet (Kerasave, AL.CHI.MI.A. S.r.l.).. Kerasave and tryptone soy broth (control) were inoculated with 10 and 10 colony-forming units (CFU)/mL of 6 Candida isolates (Candida albicans [n = 4], Candida tropicalis [n = 1], and Candida glabrata [n = 1]). Minimum inhibitory concentrations (MICs) were determined using amphotericin B Etest strips. Sterile porcine corneas contaminated with 10 CFU/mL of each isolate were incubated in Kerasave and control at 4°C. Growth rate and Log10 reduction at 4°C at different time intervals were determined for liquid samples and tissue homogenates. Kerasave biocompatibility was assessed according to ISO 10993-5 and ISO 10993-10.. No C. albicans or C. tropicalis colonies were recovered from Kerasave inoculated with 10 CFU/mL after incubation for 3 days at 4°C. C. glabrata was inhibited but not killed after 3 days at 4°C. Four of the 6 strains contaminated with 10 CFU/mL demonstrated a significant ≥ 3 Log10 reduction in media and tissue homogenates within 5 days as compared to controls (p < 0.01). Amphotericin B MICs ranged from 0.19 to 0.38 μg/mL for C. albicans (n = 3) and C. tropicalis (n = 1). C. glabrata showed reduced susceptibility (0.5 μg/mL) and 1 C. albicans was resistant to amphotericin B (≥ 1 μg/mL). Kerasave was not cytotoxic, irritating, or sensitizing according to the ISO standards.. Kerasave showed high antifungal efficacy against susceptible fungal strains at 4°C in the presence and absence of corneal tissue. Resistant strains to amphotericin B were not eliminated by Kerasave. Kerasave is not cytotoxic, irritating, or sensitizing.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candidiasis; Cornea; Disease Models, Animal; Eye Infections, Fungal; Keratitis; Microbial Sensitivity Tests; Organ Preservation; Organ Preservation Solutions; Swine

We report the case of a 61-year-old female with Crohn's disease dependent on total parenteral nutrition who developed a central venous catheter bloodstream infection and septic arthritis, complicated further by osteomyelitis and persistent

Topics: Amphotericin B; Antifungal Agents; Arthritis, Infectious; Candida glabrata; Candidiasis; Drug Resistance, Fungal; Echinocandins; Fungal Proteins; Humans; Middle Aged; Osteomyelitis; Salvage Therapy; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Fungal Proteins; Glucosyltransferases; Humans; Micafungin; Microbial Sensitivity Tests; Reactive Oxygen Species; Sequence Deletion; Trehalose

In the search for new antifungal agents, a novel series of fifteen hydrazine-thiazole derivatives was synthesized and assayed in vitro against six clinically important Candida and Cryptococcus species and Paracoccidioides brasiliensis. Eight compounds showed promising antifungal activity with minimum inhibitory concentration (MIC) values ranging from 0.45 to 31.2 μM, some of them being equally or more active than the drug fluconazole and amphotericin B. Active compounds were additionally tested for toxicity against human embryonic kidney (HEK-293) cells and none of them exhibited significant cytotoxicity, indicating high selectivity. Molecular modeling studies results corroborated experimental SAR results, suggesting their use in the design of new antifungal agents.

Topics: Antifungal Agents; Candida; Candidiasis; Cryptococcosis; Cryptococcus; HEK293 Cells; Humans; Microbial Sensitivity Tests; Models, Molecular; Paracoccidioides; Paracoccidioidomycosis; Structure-Activity Relationship; Thiazoles

Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations supporting the combination of surgery and subsequent azole treatment.. We retrospectively analyzed PVE-C cases collected in Spain and France between 2001 and 2015, with a focus on management and outcome.. Forty-six cases were followed up for a median of 9 months. Twenty-two patients (48%) had a history of endocarditis, 30 cases (65%) were nosocomial or healthcare related, and 9 (20%) patients were intravenous drug users. "Induction" therapy consisted mainly of liposomal amphotericin B (L-amB)-based (n = 21) or echinocandin-based therapy (n = 13). Overall, 19 patients (41%) were operated on. Patients <66 years old and without cardiac failure were more likely to undergo cardiac surgery (adjusted odds ratios [aORs], 6.80 [95% confidence interval [CI], 1.59-29.13] and 10.92 [1.15-104.06], respectively). Surgery was not associated with better survival rates at 6 months. Patients who received L-amB alone had a better 6-month survival rate than those who received an echinocandin alone (aOR, 13.52; 95% CI, 1.03-838.10). "Maintenance" fluconazole therapy, prescribed in 21 patients for a median duration of 13 months (range, 2-84 months), led to minor adverse effects.. L-amB induction treatment improves survival in patients with PVE-C. Medical treatment followed by long-term maintenance fluconazole may be the best treatment option for frail patients.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Disease Management; Endocarditis; Female; Fluconazole; France; Heart Valve Prosthesis; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Prosthesis-Related Infections; Registries; Retrospective Studies; Spain

Candida lusitaniae is an uncommon cause of candidiasis in humans. Ocular manifestations of C. lusitaniae infection have not been reported. C. lusitaniae is either intrinsically resistant to amphotericin B or can acquire such resistance. We describe a case of bilateral endophthalmitis due to C. lusitaniae bloodstream infection in a liver transplant patient with rectal cancer. The patient suffered fungemia and endophthalmitis and was treated with liposomal amphotericin B. The isolate was identified as C. lusitaniae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the system based on biochemical tests, and sequencing of the internal transcribed spacer region. The minimal inhibitory concentrations were 0.06 μg/mL for amphotericin B and 2.0 μg/mL for fluconazole. Repeat blood cultures were negative and the endophthalmitis improved following treatment with liposomal amphotericin B. However, the treatment was changed to fluconazole due to nephrotoxicity. No recurrence occurred after completion of treatment.

Topics: Aged; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Candida; Candidemia; Candidiasis; Catheter-Related Infections; Endophthalmitis; Eye Infections, Fungal; Fluconazole; Humans; Liver Transplantation; Male; Microbial Sensitivity Tests; Rectal Neoplasms; Risk Factors

Intercellular Candida glabrata infections are difficult to treat due to poor penetration of drugs into the fungal niche. Delivering amphotericin B (Amp B) into the macrophages where the pathogen inhabits is an effective solution. We are studying the macrophage targeting proficiency of ɩ-carrageenan for the delivery of Amp B using gelatin A nanoparticles (GNPs). The choice of gelatin A was the outcome of in silico inspections where the amino functionalized polymer having the best docking score with Amp B was selected. We prepared a sustained release formulation of amp B loaded carboxymethyl ɩ-carrageenan conjugated gelatin nanoparticles (CMC-Amp B-GNPs) with size 343±12nm and -25±5.3mV zeta potential. The formulations were found to be stable, biocompatible and non-haemolytic. Flow cytometry analysis showed 3 fold higher uptake of CMC-GNPs compared to the GNPs by RAW 264.7 cells. CMC-Amp B-GNPs showed enhanced antifungal activity than bare Amp B and Amp B-GNPs.

Topics: Amphotericin B; Animals; Candida glabrata; Candidiasis; Carrageenan; Drug Delivery Systems; Gelatin; Macrophages; Mice; Nanoparticles; RAW 264.7 Cells

Ctn[15-34], a carboxyl-terminal fragment of crotalicidin (a cathelicidin from the venom gland of a South American rattlesnake), has shown antifungal activity against clinical and standard strains of Candida species. The aim of the present work was to investigate the underlying mechanisms of the candidicidal activity of Ctn[15-34].. The time-kill profile and drug synergism were evaluated by means of a microdilution assay and multi-parametric flow cytometry. The presumptive interaction of Ctn[15-34] with lipid membranes was estimated in vitro with a lipid-mimic compound, the chromogenic substance 4-nitro-3-(octanoyloxy)benzoic acid (4N3OBA).Results/Key findings. The absorbance increment (at 425 nm) indicated a concentration- and time-dependent in-solution association between Ctn[15-34] and 4N3OBA. The interaction of Ctn[15-34] with Candida cells was confirmed by flow cytometric measurements with the 5(6)-carboxyfluorescein-labelled peptide (CF-Ctn[15-34]). Analysis of the killing time of Candida exposed to Ctn[15-34] and amphotericin B (AMB) showed that both the peptide and polyene drug reduce the number of c.f.u. but in mechanistically different ways. The Ctn[15-34] peptide alone caused yeast cell membrane disruption, which was confirmed by lactate dehydrogenase leakage and biomarkers of cell death mediated by necrosis.. Overall, Ctn[15-34] displays a synergistic antifungal activity with AMB, an effect that can be further developed into a multi-target therapeutic option with other antimycotics currently in use.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cathelicidins; Drug Synergism; Fluoresceins; Humans; Microbial Sensitivity Tests; Nitrobenzoates; Peptide Fragments; Peptides

In an effort to increase the oral bioavailability of Amphotericin B (AmB), a pH-sensitive drug carrier composed of Tragacanth (Trag) and acrylic acid (AAc) was prepared using γ-irradiation. The swelling behavior of (Trag/AAc) hydrogels was characterized as a function of pH and ionic strength of the swelling medium. The obtained swelling indices revealed the ability of the prepared hydrogel to protect a loaded drug in stomach-simulated medium (Fickian behavior) and to release such drug in intestinal-simulated medium (non-Fickian behavior). In vitro release studies of the antifungal (AmB) were performed to evaluate the hydrogel potential as a drug carrier. The antifungal activity of the prepared oral formulation was investigated in a mouse model of systemic candidiasis. Data revealed that (Trag/AAc)-AmB has a potent antifungal efficacy as demonstrated by prolonging the survival time and reducing the tissue fungal burden, serum antibody titers, as well as inflammatory cytokines in kidney and liver tissues. Furthermore, in vivo toxicity of (Trag/AAc)-AmB was assessed via measuring kidney and liver functions, and results displayed the safety of this novel AmB formulation which was confirmed by histopathological examination. Overall, results indicated that the prepared (Trag/AAc)-AmB is an effective oral delivery system for AmB with better bioavailability and minimal toxicity and could represent a promising approach for improving the therapeutic index of the drug.

Topics: Acrylates; Administration, Oral; Amphotericin B; Animals; Antibodies, Fungal; Antifungal Agents; Candida albicans; Candidiasis; Cytokines; Drug Carriers; Drug Liberation; Hydrogels; Immunoglobulin G; Immunoglobulin M; Kidney; Liver; Male; Mice; Tragacanth

Topics: Amphotericin B; Animals; Candida glabrata; Candidiasis; Chitosan; Drug Delivery Systems; Macrophages; Mice; Nanoparticles; RAW 264.7 Cells

We present a case of a rare association of infective endocarditis and a coin lesion in the lung caused by Candida albicans. The lesion disappeared after 6 weeks of treatment with 5 mg/kg/day amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Child; Echocardiography; Endocarditis; Humans; Male; Radiography, Thoracic; Rare Diseases; Solitary Pulmonary Nodule

Fungal infections are a major problem for a growing number of mostly immunocompromised patients. Candida albicans is an important human fungal pathogen causing mucosal and deep tissue infections, of which the majority are associated with biofilm formation on medical implants. Animal models that are currently in use to test antifungal drugs are limited to ex vivo analyses, requiring host sacrifice that excludes longitudinal monitoring of dynamic processes during biofilm formation in the live host. As a solution, we introduce non-invasive, dynamic imaging and quantification of C. albicans biofilm formation in vivo and subsequent evaluation of treatment efficacy against these biofilms using bioluminescent C. albicans in a catheter-associated mouse model. Bioluminescence imaging (BLI) allowed us to evaluate baseline biofilm load before the start of therapy, which is necessary for correct evaluation and interpretation of antibiofilm efficacy in vivo. Moreover, we demonstrate that this BLI approach monitors the antibiofilm activity of different antifungal agents efficiently in vitro and in vivo. In this study, BLI revealed superior antibiofilm activity for echinocandins compared with amphotericin B and fluconazole. In vitro, anidulafungin showed the highest antibiofilm activity, followed by micafungin and caspofungin. In vivo, caspofungin significantly decreased the biofilm fungal load, as documented by the lower BLI signal and confirmed by CFU counts. In conclusion, this BLI approach increases the power and efficiency of screening and validation of antimycotics both under in vitro and in vivo conditions, thereby refining pre-clinical therapy studies.

Topics: Amphotericin B; Animals; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Catheter-Related Infections; Drug Evaluation, Preclinical; Female; Fluconazole; Luminescent Measurements; Mice, Inbred BALB C

Guidance on dissolution testing for parenteral formulations is limited and not often related in vivo performance. Critically ill patients represent a target cohort, frequently hypoalbuminaemic, to whom certain parenteral formulations are administered. Amphotericin B (AmB) is a poorly soluble, highly protein-bound drug, available as lipid-based formulations and used in critical illness. The aim of this study was to develop media representing hypoalbuminaemic and healthy plasma, and to understand and simulate the dissolution profile of AmB in biorelevant media. Dissolution media were prepared with bovine serum albumin (BSA) in Krebs-Ringer buffer, and tested in a flow through cell apparatus and a bottle/stirrer setup. Drug activity was tested against Candida albicans. BSA concentration was positively associated with solubility, degradation rate and maximum amount dissolved and negatively associated with dissolution rate constant and antifungal activity. In the bottle/stirrer setup, a biexponential model successfully described simultaneous dissolution and degradation and increased in agitation reduced the discriminatory ability of the test. The hydrodynamics provided by the flow-through cell apparatus was not adequate to dissolve the drug. Establishing discriminating test methods with albumin present in the dissolution media, representing the target population, supports future development of biorelevant and clinically relevant tests for parenteral formulations.

Topics: Amphotericin B; Antifungal Agents; Buffers; Candida albicans; Candidiasis; Chemistry, Pharmaceutical; Drug Compounding; Humans; Hypoalbuminemia; Lipids; Proteins; Serum Albumin, Bovine; Solubility

Topics: Amphotericin B; Antifungal Agents; Antimicrobial Cationic Peptides; Biofilms; Candida; Candidiasis; Drug Synergism; Inhibitory Concentration 50; Microbial Sensitivity Tests; Microbial Viability; Molecular Structure; Steroids

The role of penetration limitation in Candida biofilm-associated antifungal resistance remains unclear. Most of the previous work has been done on Candida albicans, although non-albicans (NAC) species are also implicated in invasive candidiasis and the biofilm matrix has been shown to vary amongst different species. Only a few studies have evaluated clinical isolates. This study aimed to determine the relevance of penetration limitation in the antifungal resistance of biofilms formed by C. albicans and NAC clinical isolates, using an agar disk diffusion assay. The penetration of posaconazole and amphotericin B through the biofilms was significantly reduced. Fluconazole, voriconazole and caspofungin showed a superior penetration capacity in C. albicans, Candida tropicalis and Candida parapsilosis biofilms, but exhibited inter-species and strain/isolate variation. Candida krusei biofilms were the most resilient to antifungal permeation. All of the antifungal drugs failed to kill the biofilm cells, independent of penetration, suggesting that the other factors contribute markedly to the recalcitrance of the biofilms.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida; Candida albicans; Candidiasis; Drug Resistance, Fungal; Humans; Voriconazole

Invasive candidiasis is a serious pathogen of late-onset sepsis in very low birth weight infants. Kidney is the most common organ involved, and it causes morbidity and mortality, especially when fungal balls are formed. We report a 34-day-old female infant (born at 28 weeks' gestation, 1152 g) with systemic fungal infection complicated obstructive uropathy. On sonography, the fungal balls filled the entire pelvis without hydronephrosis. Percutaneous nephrostomy was not feasible. In addition to systemic antifungals, we successfully performed cystoscopy-assisted retrograde ureteral catheterization to decompress the pelvis, which also provided a route for local amphotericin B irrigation to achieve therapeutic concentration without nephrotoxicity.

Topics: Amphotericin B; Antifungal Agents; Anuria; Candidiasis; Caspofungin; Female; Flucytosine; Humans; Infant; Infant, Very Low Birth Weight; Kidney Diseases; Therapeutic Irrigation; Ultrasonography; Ureteral Obstruction; Urinary Catheterization

Multiple cases of Candida auris infection have been reported with high mortality rates owing to its MDR nature. Rezafungin (previously CD101) is a novel echinocandin with enhanced stability and pharmacokinetics that achieves high plasma drug exposure and allows for once weekly dose administration.. Evaluate the efficacy of rezafungin in the treatment of disseminated C. auris infection using a mouse model of disseminated candidiasis.. Mice were immunosuppressed 3 days prior to infection and 1 day post-infection. On the day of infection, mice were inoculated with 3 × 107C. auris blastospores via the tail vein. Mice were randomized into four groups (n = 20): rezafungin at 20 mg/kg, amphotericin B at 0.3 mg/kg, micafungin at 5 mg/kg and a vehicle control. Treatments were administered 2 h post-infection. Rezafungin was given additionally on days 3 and 6 for a total of three doses, while the remaining groups were treated every day for a total of seven doses. Five mice from each group were sacrificed on days 1, 4, 7 and 10 of the study. Kidneys were removed from each mouse to determine the number of cfu for each respective day.. Rezafungin had significantly lower average log10 cfu/g of tissue compared with amphotericin B- and vehicle-treated mice on all days when kidneys were harvested. Additionally, rezafungin-treated mice had significantly lower average log10 cfu/g of tissue compared with micafungin-treated mice on day 10.. Our findings show that rezafungin possesses potent antifungal activity against C. auris in a disseminated model of candidiasis.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candidiasis; Echinocandins; Female; Immunocompromised Host; Micafungin; Mice; Random Allocation

Hepatic fungal abscesses are rare in the neonatal period and often constitute a severe complication of the catheterization of the umbilical vessels. Such life-threatening lesions are observed more frequently in preterm than in other newborn infants and the optimal treatment remains uncertain. We present the case of a preterm neonate, who developed an intrahepatic lesion due to parenteral extravasation, successively contaminated by

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Catheters, Indwelling; Humans; Infant, Newborn; Infant, Premature; Injections, Intralesional; Intensive Care Units, Neonatal; Liver; Liver Abscess; Treatment Outcome

Chitosan, a biopolymer of immense potential, has been well-explored over the past decade in the biomedical field. Despite its numerous biological properties like anti-microbial, anti-inflammatory, anti-diabetic etc., limited studies have been conducted on its ability to protect therapeutic molecules in nano-formulations. Amphotericin B (AMP) is one such therapeutic molecule which requires protection as it possesses inherent limitations of poor water-solubility, susceptibility to oxidation- and/or light-induced degradation etc. Although AMP formulations have been quite successful in treating chronic fungal infections, their high cost, prolonged nature of therapy and instability over longer durations has necessitated the development of alternative carriers. In the present study, a stable nanoparticulate formulation was successfully prepared using low molecular weight chitosan and the anti-fungal agent AMP and this was found to offer protection to the labile AMP. The developed nanocomplexes could prevent degradation of AMP up to six months, in solution form, unlike the native drug which degraded in <24 h. Antifungal studies of the developed nanocomplexes revealed a surface charge-dependent antifungal activity. Furthermore, the nanocomplexes did not affect the viability of mammalian cells and showed excellent intracellular uptake and retention, and hence suggested potential of the nanocomplexes in alleviating systemic fungal infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Chitosan; CHO Cells; Cricetulus; Molecular Weight; Nanostructures

In recent years, there has been a significant increase in the incidence of fungal infections attributed to Candida species worldwide, with a major shift toward non-albicans Candida (NAC). In this study, we have described the distribution of Candida species among different hospital departments and calculated the antifungal consumption in our facility. We also correlated the consumption of certain antifungals and the prevalence of specific Candida species.. This was a retrospective review of all the Candida isolates recovered from the computerised microbiology laboratory database of Makassed General Hospital, a tertiary care centre in Beirut, Lebanon, between January 2010 and December 2015. Data on antifungal consumption between January 2008 and December 2015 were extracted from the hospital pharmacy electronic database. We used Spearman's coefficient to find a correlation between Candida species distribution and antifungal consumption.. Between 2008 and 2015, we observed that the highest antifungal consumption was in the haematology/oncology department (days of therapy/1000 patient days = 348.12 ± 85.41), and the lowest was in the obstetrics/gynaecology department (1.36 ± 0.47). In general, the difference in antifungal consumption among various departments was statistically significant (P < 0.0001). Overall, azoles were the most common first-line antifungals in our hospital. Echinocandins and amphotericin B were mostly prescribed in the haematology/oncology department. As for Candida species distribution, a total of 1377 non-duplicate isolates were identified between 2010 and 2015. A non-homologous distribution of albicans vs. non-albicans was noted among the different departments (P = 0.02). The most commonly isolated NAC was Candida glabrata, representing 14% of total Candida species and 59% of NAC. Candida famata (9% of NAC), Candida parapsilosis (3.6% of NAC) and Candida krusei (3% of NAC) were recovered unequally from the different departments. The total antifungal consumption correlated positively with the emergence of NAC. The use of azoles correlated positively with Candida glabrata, while amphotericin B formulations correlated negatively with it. None of these correlations reached statistical significance.. Different Candida species were unequally distributed among different hospital departments, and this correlated with consumption of antifungals in respective departments, highlighting the need for antifungal stewardship.

Topics: Academic Medical Centers; Adult; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candidiasis; Child; Drug Resistance, Fungal; Echinocandins; Female; Hospital Departments; Humans; Incidence; Lebanon; Male; Microbial Sensitivity Tests; Mycoses; Retrospective Studies

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candida albicans; Candidiasis; Caspofungin; Drug Resistance, Fungal; Fluconazole; Humans; Nystatin; Oils, Volatile; Voriconazole

The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicrobial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N'-aryl-bishydrazones for their antibacterial and antifungal activities against panels of Gram-positive/Gram-negative bacteria as well as fungi. We investigated their potential to develop resistance against both bacteria and fungi by a multi-step resistance-selection method, explored their potential to induce the production of reactive oxygen species, and assessed their toxicity. In summary, we found that these compounds exhibited broad-spectrum antibacterial and antifungal activities against most of the tested strains with minimum inhibitory concentration (MIC) values ranging from <0.5 to >500μM against bacteria and 1.0 to >31.3μg/mL against fungi; and in most cases, they exhibited either superior or similar antimicrobial activity compared to those of the standard drugs used in the clinic. We also observed minimal emergence of drug resistance to these newly synthesized compounds by bacteria and fungi even after 15 passages, and we found weak to moderate inhibition of the human Ether-à-go-go-related gene (hERG) channel with acceptable IC

Topics: Anti-Bacterial Agents; Antifungal Agents; Bacteria; Bacterial Infections; Candida albicans; Candidiasis; Cell Line; Drug Discovery; Drug Resistance, Multiple; Fungi; Humans; Hydrazones; Microbial Sensitivity Tests; Mycoses

Fluconazole (FLC) is the drug of choice when it comes to treat fungal infections such as invasive candidiasis in humans. However, the widespread use of FLC has resulted in the development of resistance to this drug in various fungal strains and, simultaneously has occasioned the need for new antifungal agents. Herein, we report the synthesis of 27 new FLC derivatives along with their antifungal activity against a panel of 13 clinically relevant fungal strains. We also explore their toxicity against mammalian cells, their hemolytic activity, as well as their mechanism of action. Overall, many of our FLC derivatives exhibited broad-spectrum antifungal activity and all compounds displayed an MIC value of <0.03 μg/mL against at least one of the fungal strains tested. We also found them to be less hemolytic and less cytotoxic to mammalian cells than the FDA approved antifungal agent amphotericin B. Finally, we demonstrated with our best derivative that the mechanism of action of our compounds is the inhibition of the sterol 14α-demethylase enzyme involved in ergosterol biosynthesis.

Topics: Alkylation; Animals; Antifungal Agents; Azoles; Candida albicans; Candidiasis; Cell Line; Ergosterol; Fungi; Hemolysis; Humans; Mice; Microbial Sensitivity Tests; Mycoses

The d-Phe-Pro β-turn of the cyclic β-hairpin antimicrobial decapeptide tyrocidine A, (Tyrc A) was substituted with the d-Phe-2-aminobenzoic acid (2-Abz) motif in a synthetic analogue (1). The NMR structure of 1 demonstrated that compound 1 retained the β-hairpin structure of Tyrc A with additional planarity, resulting in approximately 30-fold reduced hemolysis than Tyrc A. Although antibacterial activity was partially compromised, a single Gln to Lys substitution (2) restored activity equivalent to Tyrc A against S. aureus, enhanced activity against two Gram negative strains and maintained the reduced hemeloysis of 1. Analysis by transmission electron microscopy (TEM) suggested a membrane lytic mechanism of action for these peptides. Compound 2 also exhibits nanomolar antifungal activity in synergy with amphotericin B. The d-Phe-2-Abz turn may serve as a tool for the synthesis of structurally predictable β-hairpin libraries. Unlike traditional β-turn motifs such as d-Pro-Gly, both the 2-Abz and d-Phe rings may be further functionalized.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Bacteria; Bacterial Infections; Candida albicans; Candidiasis; Escherichia coli; Hemolysis; Humans; Models, Molecular; Staphylococcal Infections; Staphylococcus aureus; Tyrocidine

Yeasts frequently colonize non-sterile sites in the body. The aim of the study was to determine distribution in clinical samples and antifungal susceptibility to five antifungals. From January 2013 through June 2015, 800 isolates were obtained from intensive care unit patients. Candida albicans (58.9%), Candida glabrata (20.4%), Candida krusei (8.6%), and Candida parapsilosis (3.6%) were the leading species. Majority of the C. albicans isolates were susceptible to the fluconazole. Elevated voriconazole minimal inhibitory concentrations (MICs) were observed in isolates exhibiting high fluconazole MICs, most frequently in C. glabrata. Isolates with echinocandins MICs suggesting reduced susceptibility were only sporadic cases with the exception of Trichosporon spp. The amphotericin B MICs were slightly higher for some C. krusei.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Fluconazole; Humans; Intensive Care Units; Microbial Sensitivity Tests; Voriconazole

Amphotericin B (AmB) has been widely used against fungal infections throughout almost the entire body, including the skin, nails, oral cavity, respiratory tract, and urinary tract. However, the development of AmB-loaded nanoparticles demands a novel technique that reduces its toxicity and other associated problems. Here, we developed a pH-responsive and redox-sensitive polymer-based AmB-delivery carrier system. In particular, this system was functionalized by conjugation with the antifungal peptide histatin 5, which acts both as a targeting ligand and a synergistic antifungal molecule against Candida albicans, a major systemic fungal pathogen of humans. Our results in vitro and in vivo suggest that this drug-delivery system may serve as a novel tool to facilitate the use of antimicrobial peptides as targeting ligands to pathogenic microbes, which would open new avenues of investigation in the field of drug delivery.

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Antifungal Agents; Candida albicans; Candidiasis; Cell Line; Cell Survival; Cysteamine; Drug Delivery Systems; Drug Liberation; Drug Synergism; Erythrocytes; Female; Hemolysis; Histatins; Humans; Mice, Inbred ICR; Polymers; Rats

Infective endocarditis is a disease characterised by heart valve lesions, which exhibit extracellular matrix proteins that act as a physical barrier to prevent the passage of antimicrobial agents. The genus Candida has acquired clinical importance given that it is increasingly being isolated from cases of nosocomial infections.. To evaluate the activity of caspofungin compared to that of liposomal amphotericin B against Candida albicans in experimental infective endocarditis.. Wistar rats underwent surgical intervention and infection with strains of C. albicans to develop infective endocarditis. Three groups were formed: the first group was treated with caspofungin, the second with liposomal amphotericin B, and the third received a placebo. In vitro sensitivity was first determined to further evaluate the effect of these treatments on a rat experimental model of endocarditis by semiquantitative culture of fibrinous vegetations and histological analysis.. Our semiquantitative culture of growing vegetation showed massive C. albicans colonisation in rats without treatment, whereas rats treated with caspofungin showed significantly reduced colonisation, which was similar to the results obtained with liposomal amphotericin B.. The antifungal activity of caspofungin is similar to that of liposomal amphotericin B in an experimental model of infective endocarditis caused by C. albicans.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Caspofungin; Disease Models, Animal; Echinocandins; Endocarditis; Female; Lipopeptides; Rats; Rats, Wistar

To determine Candida colonisation/infection in renal transplant patients and to determine the resistance pattern against antifungal drugs.. This prospective, observational study was conducted at Al-Sayyed Hospital, Rawalpindi, Pakistan, from January to October 2014, in collaboration with the Microbiology and Public Health Laboratory's, Islamabad campus..The clinical specimens investigated included respiratory tract secretions, blood, urine, high vaginal swab, skin scrapings, and plastic devices samples.. Of the 7,850 samples, 164(2.08%) were positive for Candida. Candida albicans were most prevalent as they were found in 114(69%) samples. Besides, 56(34%) of the positive samples were resistant to one or more antifungal agents. Highest resistance was obtained against fluconazole. We found only 5(3.04%) positive samples of Candida glabrata; of them, 3(60%)were resistant. In case of Candida spp, 27(48%) resistance was observed. In Candida albicans, 23(41%) of the samples were found to be resistant. Most of the Candida isolates was recovered from bronchial alveolar lavage.. Although Candida albicans remained the main responsible species for Candida infections, but non-albican Candida species are also emerging.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candida glabrata; Candidiasis; Cross-Sectional Studies; Drug Resistance, Fungal; Fluconazole; Humans; Ketoconazole; Kidney Failure, Chronic; Kidney Transplantation; Microbial Sensitivity Tests; Pakistan; Prevalence; Prospective Studies; Tertiary Care Centers; Voriconazole

To demonstrate the feasibility and safety of weekly high-dose liposomal amphotericin B (L-AmB) (as a pre-emptive antifungal treatment) for 2 weeks in patients with septic shock and Candida colonization.. Pilot, multicentre, open-label, prospective study conducted in seven French ICUs. Non-immunocompromised patients, receiving mechanical ventilation were eligible if they presented ICU-acquired severe sepsis requiring newly administered antibacterial agents and Candida colonization in at least two sites. Exclusion criteria included the need for antifungal therapy and creatinine > 220 μmol/L. All patients were to receive a high-dose L-AmB (10 mg/kg/week) for two weeks. A follow-up period of 21 days following the second administration of L-AmB was conducted. Treated patients were compared to 69 matched untreated controls admitted in the same ICUs before the study period.. Twenty-one patients were included in the study, of which 20 received at least one infusion of high-dose L-AmB. A total of 24 adverse events were identified in 13(61%) patients. Fourteen adverse events were categorized as serious in 8(38%) patients. In four cases the adverse events were considered as potentially related to study drug administration and resulted in L-AmB discontinuation in one patient. Few patients experienced severe renal toxicity since no patient presented with severe hypokalemia. No patients required renal replacement therapy. Compared to matched controls, no significant increase in serum creatinine levels in patients receiving high-dose L-AmB was reported.. Weekly administration of high-dose L-AmB has a manageable safety profile and is feasible in patients with ICU-acquired sepsis and multiple Candida colonization. Trials of L-AmB versus other antifungal agents used as pre-emptive antifungal therapy are warranted.. ClinicalTrials.gov NCT00697944.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Critical Illness; Cross Infection; Female; Humans; Intensive Care Units; Male; Middle Aged; Pilot Projects; Prospective Studies; Sepsis; Treatment Outcome

Candida species bloodstream infection, or candidemia, remains an important health issue with high morbidity and mortality. Bloodstream infections caused by Candida species are often associated with the ability of Candida to form biofilms on medical devices, such as central venous catheters. Non-albicans Candida species have been increasing gradually in clinical settings. Another Candida species, C. tropicalis, has a propensity to form biofilms and is also an independent risk factor for high morbidity and mortality in hospitalized patients. This study was conducted to investigate the process of biofilm formation by C. tropicalis and the antifungal activity of liposomal amphotericin B (LAB) against both forming biofilms and developed biofilms using time-lapse imaging. We found that C. tropicalis has a high capacity for hyphal growth and gas generation due to its high metabolic activity. Thus, we visually observed the formation of aggressive C. tropicalis biofilms, which are fast-growing biofilms. We found that LAB acts immediately and completely inhibits forming biofilms. Furthermore, we demonstrated that LAB was effective against developed C. tropicalis biofilms by reducing the growth of hyphae and morphological changes. These results suggest that LAB may be effective for the treatment of infections caused by catheter-related C. tropicalis biofilms.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida tropicalis; Candidiasis; Gases; Humans; Hyphae; Japan; Time-Lapse Imaging

The present study was designed to develop a nanoemulsion formulation of Amphotericin B (AmB) for the treatment of skin candidiasis and aspergillosis. Several ingredients were selected on the basis of AmB solubility and compatibility with skin. The formulation that exhibited the best properties was selected from the pseudo-ternary phase diagram. After physicochemical characterization its stability was assessed. Drug release and skin permeation studies were also accomplished. The antifungal efficacy and skin tolerability of developed AmB nanoemulsion was demonstrated. Finally, our results showed that the developed AmB formulation could provide an effective local antifungal effect without theoretical systemic absorption, based on its skin retention capacity, which might avoid related side effect. These results suggested that the nanoemulsion may be an optimal therapeutic alternative for the treatment of skin fungal infections with AmB.

Topics: Administration, Topical; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Candida; Candidiasis; Dermatomycoses; Emulsions; Female; Humans; Pharmaceutical Vehicles; Skin; Skin Absorption

In recent years, the infection Candida albicans infection worldwide has risen, and the incidence of resistance to traditional antifungal therapies is also increasing. The aim of this study was to evaluate in vitro susceptibility of C. albicans clinical isolates to eight antifungal agents in Ouagadougou.. A cross-sectional study was conducted from January 2013 to December 2015 at Yalgado Ouédraogo University Teaching Hospital. Two hundred seven strains have been isolated from 347 symptomatic patients received in different clinical services. Samples were cultured on Sabouraud Dextrose Agar supplemented with Cloramphenicol. Isolates were diagnosed as C. albicans using germ tube test, chlamydospore formation on Corn Meal Agar, and Api-Candida test (Biomérieux). Antifungal susceptibility testing was performed by disk diffusion method and isolates classified as susceptible, susceptible dose-dependent and resistant.. Three hundred forty-seven (347) patients are included in this study. Two hundred and six (206) out of 347 collected samples (59.36%) were found positive for C. albicans. The strains were mostly isolated from vulvovaginal (49%) and oral infections (40.3%). The highest resistance rates of azoles were obtained with fluconazole (66.5%), itraconazole (52.3%) and ketoconazole (22.9%) when all clinical isolates were included. The resistance rates of fluconazole, itraconazole and ketoconazole remain highest for vulvovaginal and oral isolates. The rate of resistance to the polyene amphotericin B was 32.0% for all clinical isolates and was 56.4% for vulvovaginal strains. Resistance rate to nystatin was 6.3% for all clinical isolates. Cross-resistance analysis with data of all clinical strains revealed that the incidence of resistance to ketoconazole and itraconazole in fluconazole-resistant isolates was significantly higher than recorded for fluconazole-susceptible isolates.. In vitro C. albicans antifungal susceptibility test in this study showed relatively high resistance to commonly and widely used azoles (fluconazole, ketoconazole). Most C. albicans clinical isolates were susceptible to nystatin.

Topics: Adult; Amphotericin B; Antifungal Agents; Burkina Faso; Candida albicans; Candidiasis; Candidiasis, Oral; Candidiasis, Vulvovaginal; Cross-Sectional Studies; Drug Resistance, Fungal; Female; Fluconazole; Humans; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged

To determine the prevalence and antifungal susceptibility pattern of Candida species.. This prospective, cross-sectional study was conducted at the Quaid-e-Azam International Hospital, Islamabad, Pakistan, from January 2014 to February 2015, and comprised different clinical samples which were analysed for various types of microbial infections. Species differentiation was confirmed by biochemical and molecular methods. Antifungal susceptibility against amphotericin B, fluconazole and voriconazole was determined by Clinical and Laboratory Standards Institute M44-A disk diffusion method.. Of the 219 Candida isolates, majority of them were isolated from urine 78(35.6%) and vaginal swabs 59(26.9%). Moreover, 144(65.8%) samples were of females and 75(34.2%) were of males. Candida albicans 128(58.45%) was the most predominant species followed by Candida glabrata 30(13.69%), Candida tropicalis 26(11.87%), Candida krusei 17(7.76%), Candida parapsilosis 12(5.47%), Candida dubliniensis 3(1.37%) and Candida lusitaniae 3(1.37). All isolates were least susceptible to amphotericin B with a susceptibility rate of 213(97.26%). The highest resistance was found for voriconazole 40(18.26%) compared to fluconazole 32(14.61%).. Candida species possessed high resistance rate against various antifungal agents.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidiasis; Candidiasis, Vulvovaginal; Child; Child, Preschool; Cross-Sectional Studies; Drug Resistance, Fungal; Female; Fluconazole; Humans; Infant; Infant, Newborn; Inpatients; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Epidemiology; Outpatients; Pakistan; Prevalence; Prospective Studies; Respiratory Tract Infections; Tertiary Care Centers; Urinary Tract Infections; Voriconazole; Young Adult

To determine the type of Candida species in ocular infections and to investigate the relationship of antifungal susceptibility profile to virulence factors.. Fifty isolates of yeast-like fungi from patients with keratitis, endophthalmitis, and orbital cellulitis were identified by Vitek-2 compact system and DNA sequencing of ITS1-5.8S-ITS2 regions of the rRNA gene, followed by phylogenetic analysis for phenotypic and genotypic identification, respectively. Minimum inhibitory concentration of six antifungal drugs was determined by E test/microbroth dilution methods. Phenotypic and genotypic methods were used to determine the virulence factors.. Phylogenetic analysis showed the clustering of all isolates into eight distinct groups with a major cluster formed Candida parapsilosis (n = 21), which was the most common species by both Vitek 2 and DNA sequencing. Using χ2 test no significant difference was noted between the techniques except that Vitek 2 did not identify C. viswanathii, C. orthopsilosis, and two non-Candida genera. Of 43 tested Candida isolates high susceptibility to amphotericin B (39/43, 90.6%) and natamycin (43/43, 100%) was noted. While none of the isolates produced coagulase, all produced esterase and catalase. The potential to form biofilm was detected in 23/43 (53.4%) isolates. Distribution of virulence factors by heat map analysis showed difference in metabolic activity of biofilm producers from nonbiofilm producers.. Identified by Vitek 2 and DNA sequencing methods C. parapsilosis was the most common species associated with eye infections. Irrespective of the virulence factors elaborated, the Candida isolates were susceptible to commonly used antifungal drugs such as amphotericin B and natamycin.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Biofilms; Candida; Candidiasis; Child, Preschool; Endophthalmitis; Eye Infections, Fungal; Female; Humans; Keratitis; Male; Microbial Sensitivity Tests; Middle Aged; Natamycin; Orbital Cellulitis; RNA, Fungal; RNA, Ribosomal; Sequence Analysis, DNA; Virulence Factors; Young Adult

Oral candidiasis or thrush is a fungal infection due to Candida albicans, causing discomfort in areas inside mouth or tongue. The clinical application of antifungal reagent amphotericin B (AMB), which is believed to offer a better treatment for oral candidiasis, is greatly compromised by its toxicities (mainly nephrotoxicity) and poor solubility. In order to overcome these issues, we characterized AMB-loaded MPEG-PCL micelles in vitro and in vivo. In addition, the antifungal activities of AMB/MPEG-PCL micelles-loaded buccal tablet were also evaluated in vitro. We found that micelles system could significantly improve the solubility of AMB yet reduce the overall toxicity, while the buccal tablet system is capable to suppress C. albicans biofilm formation. Furthermore, the toxicity of the buccal tablet system is also reduced compared with other standard preparations. Therefore, the prepared tablet with AMB-loaded MPEG-PCL micelles as oral topical preparations has the potential to improve current treatment of superficial oral C. albicans infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Male; Micelles; Nanoparticles; Polyesters; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Tablets; Toxicity Tests

The purpose of this study was to develop a more efficient drug delivery device to overcome the limitations of current drop therapy for the treatment of fungal keratitis.. Amphotericin B (AmpB), 0 to 30 μg/mL, was associated with a poly-ε-lysine (pεK) hydrogel. Fungicidal effect against Candida albicans was assessed at 18 and 42 hours by optical density (OD600) and growth on agar. Tear film dilution effect was mimicked by storage of AmpB pεK gels in 3.4 mL sterile PBS for 24 hours prior to fungal incubation. Drug elution over 96 hours was evaluated by HPLC, and drug stability was tested while associated with the gel by OD600 up to 48 hours. Lack of cytotoxicity toward the HCE-T corneal epithelial cell line was assessed over 7 days.. AmpB pεK gels show fungicidal activity in normal conditions (0.057 OD600, SD 0.003, P < 0.005) and in the presence of horse serum (0.048 OD600, SD 0.028 P < 0.005) at 18 hours. The drug release profile was above therapeutic levels (0.188 μg/mL) for up to 72 hours. Tear dilution had no significant effect at higher concentrations of AmpB (3 to 10 μg/mL). AmpB pεK gels were not cytotoxic to the HCE-T cell line.. We demonstrated that AmpB pεK gels confer sustained therapeutic antifungal activity for at least 48 hours without corneal epithelial cell line cytotoxicity, suggesting their potential for in vivo use as an antifungal bandage contact lens. This could avoid the need for intensive topical medication in the treatment of fungal keratitis.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Cell Line; Cell Survival; Chromatography, High Pressure Liquid; Contact Lenses; Corneal Ulcer; Drug Carriers; Drug Delivery Systems; Epithelium, Corneal; Eye Infections, Fungal; Humans; Polylysine

Topics: Aloe; Amphotericin B; Animals; Antifungal Agents; Biomimetic Materials; Candida albicans; Candidiasis; Cell Line; Mice; Mice, Inbred BALB C; Nanoparticles; Plant Extracts; Plant Leaves

To report the successful medical management of a late-onset Descemet membrane endothelial keratoplasty (DMEK)-related interface infection.. A case of DMEK endothelial keratoplasty-related infection treated with intrastromal antifungal injection was identified. The following information was collected: demographic data, surgical indications, donor rim cultures, donor mate outcomes, clinical course, diagnostic tests, and clinical outcome.. A DMEK patient developed a single infiltrate approximately 1 month after uncomplicated DMEK. Donor rim culture was positive for Candida glabrata but no prophylactic treatment was initiated. Anterior segment optical coherence tomography confirmed the location of the infiltrate, and the patient was treated with oral fluconazole and an intrastromal injection of amphotericin B with an inadvertent, but negligible, intracameral volume of the same drug. The lesion significantly regressed on examination 2 days later with complete involution and excellent visual acuity to date.. Medical therapy, including systemic and intrastromal application, is a viable initial treatment option for late-onset, presumed yeast interface keratitis in patients who have undergone DMEK.

Topics: Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Chemotherapy, Adjuvant; Descemet Stripping Endothelial Keratoplasty; Drug Therapy, Combination; Eye Infections, Fungal; Female; Fluconazole; Humans; Injections, Intraocular; Middle Aged; Postoperative Complications

The aim of this study was to identify Candida spp. isolated from candiduria episodes at a tertiary hospital in the Midwest region of Brazil, and to determine their susceptibility profiles to antifungal compounds. From May 2011 to April 2012, Candida spp. isolated from 106 adult patients with candiduria admitted to the University Hospital of the Federal University of Mato Grosso do Sul were evaluated. Both, species identification and susceptibility testing with fluconazole-FLC, voriconazole-VRC, and amphotericin B-AmB were carried out using the Vitek 2. To discriminate species of the C. parapsilosis complex, a RAPD-PCR technique using the RPO2 primer was performed. From the total of 106 isolates, 42 (39.6%) C. albicans and 64 (60.4%) Candida non-albicans (CNA) - 33 C. tropicalis, 18 C. glabrata, 5 C. krusei, 4 C. parapsilosis sensu stricto, 2 C. kefyr, 1 C. lusitaniae, and 1 C. guilliermondii were identified. All isolates were susceptible to AmB and VRC, whereas all C. glabrata isolates presented either resistance (5.6%) or dose-dependent susceptibility (94.4%) to FLC. The study of Candida spp. and their resistance profiles may help in tailoring more efficient therapeutic strategies for candiduria.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Brazil; Candida; Candidiasis; Drug Resistance, Fungal; Electrophoresis, Agar Gel; Female; Fluconazole; Hospitals, University; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Random Amplified Polymorphic DNA Technique; Treatment Outcome; Urinary Tract Infections; Voriconazole; Young Adult

We present a case of rice body formation in the left knee joint of a 2-month-old infant affected by Candida albicans septic arthritis which has never been reported before. Rice body formation has been described in association with rheumatoid or tuberculous arthritis and is very rare in Candida arthritis. After three weeks of therapy with amphotericin B administered intravenously, the infant recovered fully from infection. Septic arthritis is a serious cause of morbidity and for proper evaluation and treatment fungal septic arthritis should be included in the differential diagnosis.

Topics: Amphotericin B; Antifungal Agents; Arthritis, Infectious; Candidiasis; Female; Fluconazole; Humans; Hypertrophy; Infant; Joint Loose Bodies; Knee Joint; Synovial Membrane

To report the outcomes of primary transconjunctival 23-gauge (23-G) vitrectomy in the diagnosis and treatment of presumed endogenous fungal endophthalmitis (EFE).. Retrospective analysis of patients with EFE who underwent diagnostic transconjunctival 23-G vitrectomy at a tertiary referral center.. Nineteen eyes of 15 patients with EFE were included in the study. Four patients had bilateral and 11 patients unilateral disease. Sixteen eyes of 15 patients underwent 23-G vitrectomy to confirm the diagnosis using vitreous culture, polymerase chain reaction, and histopathologic examinations. All affected eyes were treated with intravitreal amphotericin B 5 µg/0.1 mL. Fourteen patients received additional systemic antifungal therapy. Diagnostic 23-G vitrectomy confirmed the diagnosis of EFE in 75% of the eyes (12/16). Candida was found to be a causative agent in 62.5% and Aspergillus in 12.5% of the eyes. Retinal detachment was the most common complication (42% of eyes).. EFE can be easily confirmed using primary 23-G vitrectomy.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Conjunctiva; Endophthalmitis; Eye Infections, Fungal; Female; Fungi; Humans; Intravitreal Injections; Male; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Tertiary Care Centers; Treatment Outcome; Visual Acuity; Vitrectomy; Vitreous Body

Funguria occurs often in hospitalized patients and is most commonly caused by Candida species. Fluconazole is the agent of choice for most Candida urinary tract infections. Amphotericin B bladder irrigations (ABBI) are an alternative treatment option.. The purpose of this study is to assess the efficacy of ABBI compared to fluconazole for the treatment of candiduria in the intensive care unit (ICU) setting.. We conducted a retrospective chart review of patients admitted to ICUs at our institution with a positive urine culture for Candida species between 2005 and 2012. All patients receiving ABBI were included; patients receiving fluconazole for treatment of candiduria were matched by year. The primary endpoint was achievement of cure.. There was no difference in cure between the ABBI and fluconazole groups (59.6% vs. 52.8%, p = 0.55). Clearance was higher in patients receiving ABBI (92.3% vs. 67.9%, p < 0.001). Logistic regression found that renal dysfunction predicted greater cure with ABBI therapy compared to fluconazole (OR 7.63, 95% CI 1.81-32.1).. ABBI was equally efficacious in achieving overall cure, and resulted in greater clearance of candiduria compared to fluconazole. ABBI may be considered an alternative to fluconazole for the treatment of candiduria and may be preferred over fluconazole in patients with renal dysfunction.

Topics: Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Cross Infection; Female; Fluconazole; Humans; Intensive Care Units; Male; Middle Aged; Retrospective Studies; Therapeutic Irrigation; Treatment Outcome; Urinary Bladder; Urinary Tract Infections

To compare the safety and efficacy of intravitreal anidulafungin injection with voriconazole and amphotericin B (Amp B) in an experimental Candida endophthalmitis (CE) model.. Total clinical scores were significantly different between treatment groups and the control group (p < 0.05). On day 7 of the therapy, clinical scores of the anidulafungin group were found to be significantly lower when compared with the other therapy groups, while a significant improvement was observed in the eyes of rabbits in the anidulafungin group (p < 0.05). Also, microbiological scores of the anidulafungin group were lower than those of the control group (p < 0.05). Histopathological scores of the anidulafungin treatment group were significantly better than the voriconazole and control groups. Inflammation was evidently suppressed and marked retinal toxicity was not observed with anidulafungin.. This is the first study comparing the efficacy of anidulafungin with other antifungal agents. In this CE model, an intravitreal single dose of anidulafungin was shown to be noninferior to voriconazole and Amp B. As an alternative to Amp B or voriconazole, intravitreal anidulafungin is suggested as an effective antifungal agent for the treatment of CE.

Topics: Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Candida albicans; Candidiasis; Conjunctiva; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Echinocandins; Endophthalmitis; Eye Infections, Fungal; Intravitreal Injections; Iris; Male; Rabbits; Vitreous Body; Voriconazole

Topics: Aged; Amphotericin B; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antifungal Agents; Biopsy; Candidiasis; Diagnosis, Differential; Female; Humans; Lichen Planus, Oral; Psoriasis

Use of intra-articular antibiotics for the treatment of arthroplasty infections has gained some interest over the last few years.. Some data exists on its use with bacterial arthroplasty infections.. We used intra-articular amphotericin B in an attempt to cure these joint infections and perform a one stage revision.. Two patients were treated with intra-articular amphotericin B for 6 weeks followed by suppressive fluconazole for 4 months. Intra-articular joint fluid was cultured during this process for re-growth of fungus.. Both patients were treated successfully with the method with follow up showing no evidence of recurrence. IA administration of amphotericin B may be an alternative treatment in these patients.

Topics: Aged; Amphotericin B; Antifungal Agents; Arthroplasty, Replacement, Knee; Candida; Candidiasis; Communicable Diseases; Female; Fluconazole; Humans; Injections, Intra-Articular; Knee Prosthesis; Male; Prosthesis-Related Infections; Synovial Fluid; Treatment Failure

We aimed to investigate whether mutations and/or overexpressions of ERG4 and ERG11 genes were involved in drug resistance to azoles in Candida albicans.. Totally, 34 clinical isolates of C. albicans were included in this study. Antimicrobial susceptibility tests, including 5-fluorocytosine (5-FC), amphotericin B (AMB), fluconazole (FCA), itraconazole (ITR), and voriconazole (VRC), were performed by broth microdilution method. Mutations in the ERG4 and ERG11 genes sequence were detected. The messenger RNA (mRNA) levels of ERG4 and ERG11 were measured by quantitative real-time polymerase chain reaction. The correlation of the expression levels of ERG4 with ERG11 genes in susceptible isolates and resistant isolates was analyzed by Pearson's correlation analysis.. Among 34 C. albicans isolates, 52.94%, 70.59%, and 50.00% isolates were resistant to FCA, ITR, and VRC, respectively. Sequencing results revealed that only 2 silent mutations were found in ERG4 gene, while 10 amino acid substitutions, including 6 reported previously and 4 new identified, were frequently found in ERG11 gene. The mRNA levels of ERG4 and ERG11 genes were significantly elevated in resistant compared with susceptible C. albicans isolates. Furthermore, the mRNA level of ERG4 was positively correlated with ERG11 in susceptible but not resistant C. albicans isolates.. The resistance to azoles may be associated with the mutations in ERG11 but not ERG4 gene in C. albicans isolates. In addition, overexpressed ERG4 and ERG11 genes are found in resistant C. albicans isolates, and the mRNA levels of ERG4 may be irrelevant to ERG11 in resistant C. albicans isolates.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Cytochrome P-450 Enzyme System; Drug Resistance, Fungal; Fluconazole; Flucytosine; Fungal Proteins; Gene Expression; Humans; Itraconazole; Microbial Sensitivity Tests; Mutation; Oxidoreductases; RNA, Messenger; Sequence Analysis, DNA; Voriconazole

Topics: Administration, Cutaneous; Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Candida albicans; Candidiasis; Emulsions; Excipients; Humans; Rats; Skin; Skin Absorption

This study reports design and evaluation of chitosan-based microparticle activity against Candida glabrata in vitro and in vivo in immunocompetent mice model artificially maintained in oestrus state. Because their flattened shape, chitosan microparticles are called here micro-platelets. They were obtained by self-association of oleoyl chitosan and α-cyclodextrin in water. A mixture of amphotericin B-deoxycholate (Fungizone

Topics: Amphotericin B; Animals; Antifungal Agents; Candida glabrata; Candidiasis; Chitosan; Cyclodextrins; Deoxycholic Acid; Drug Combinations; Immunocompromised Host; Mice; Mucous Membrane

The aim of this work is to design new chitosan conjugates able to self-organize in aqueous solution in the form of micrometer-size platelets. When mixed with amphotericin B deoxycholate (AmB-DOC), micro-platelets act as a drug booster allowing further improvement in AmB-DOC anti-Candida albicans activity.. Micro-platelets were obtained by mixing oleoyl chitosan and α-cyclodextrin in water. The formulation is specifically-engineered for mucosal application by dispersing chitosan micro-platelets into thermosensitive pluronic. These results demonstrate for the first time the ability of flattened chitosan micro-platelets to have synergistic activity with AmB-DOC against C. albicans candidiasis and highlight the importance of rheological and mucoadhesive behaviors of hydrogels in the efficacy of the treatment.

Topics: alpha-Cyclodextrins; Amphotericin B; Animals; Antifungal Agents; Blood Platelets; Candida albicans; Candidiasis; Chemistry, Pharmaceutical; Chitosan; Deoxycholic Acid; Disease Models, Animal; Drug Combinations; Female; Hydrogels; Mice; Mice, Inbred BALB C; Mucous Membrane; Nanoparticles; Poloxamer; Swine

Fungemia due to uncommon/rare Candida species is an emerging problem of global clinical significance. Here, we describe a case of Candida conglobata bloodstream infection in a preterm neonate. The diagnosis was established by repeated isolation of C. conglobata in blood cultures and by detection of rDNA of the fungus in serum samples. The identity of the isolate as C. conglobata was confirmed by sequencing of ITS region and D1/D2 domains of rDNA. Despite initial treatment with a liposomal amphotericin B (AmBisome) for 7 days, the blood culture remained positive. The neonate was successfully treated by combination therapy with caspofungin for 25 days. To the best of our knowledge, this is the first proven report unequivocally proving the etiologic role of C. conglobata in bloodstream infection.

Topics: Amphotericin B; Antifungal Agents; Candidemia; Candidiasis; Caspofungin; Catheter-Related Infections; Drug Therapy, Combination; Echinocandins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lipopeptides; Male; Treatment Outcome

Amphotericin B (AmB) and 5-fluorocytosine (5-FC) exhibit additive to synergistic activity against systemic mycoses. Incompatibility of prescribed formulations precludes concomitant IV administration, a route with distinct advantages. Previously, we used PEG-DSPE micelles to produce a reformulation of Fungizone (AmB-SD), AmB solubilized by sodium deoxycholate, called mAmB-90. Herein, we describe a second reformulation that facilitates co-delivery of mAmB-90 and 5-FC, and evaluate the effect of PEG-DSPE micelles on the combination's activity against Candida albicans.. We assessed the effect of 5-FC addition on the stability, in vitro toxicity, and antifungal efficacy of mAmB-90. The aggregation state and particle size of mAmB-90 combined with 5-FC (FmAmB-90) was evaluated over 48 h. Hemolytic activity was measured in vitro. Antifungal activity was determined in vitro against C. albicans. The efficacy of monotherapy and combination treatment was evaluated in a neutropenic mouse model of disseminated candidiasis.. The aggregation state, particle size, and hemolytic activity of mAmB-90 were unaffected by 5-FC. While antifungal activity was similar in vitro, mAmB-90 alone and combined with 5-FC was more potent than AmB-SD in vivo.. Short-term stability and in vivo efficacy of our formulation suggest potential to simultaneously deliver AmB and 5-FC for potent antifungal efficacy.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Chemistry, Pharmaceutical; Deoxycholic Acid; Drug Carriers; Female; Flucytosine; Mice; Mice, Inbred ICR; Micelles; Particle Size; Phosphatidylethanolamines; Polyethylene Glycols; Sodium; Sodium Chloride

Systemic fungal infections are an increasingly prevalent health problem, especially among immunocompromised patients. Antifungal drug development lags far behind in comparison to other types of antimicrobial drugs. Current commercially available antifungals are limited by their insufficient potency, side effects, drug-drug interactions, developing drug-resistance, and narrow formulation options. Here, we report the preparation and evaluation of two novel PEG amide conjugates of amphotericin B (AMB (1)): AB1 (4) and AM2 (5). These compounds are nonlabile, they are prepared in only two and three synthetic steps, respectively, and they show antifungal activity against a wide range of clinical fungal isolates. Their toxicity is significantly lower, and their water solubility is up to 5000-fold higher than that of AMB (1). In vivo efficacy studies in a mouse model of systemic candidiasis showed that AM2 (5) successfully cured all the mice at concentrations above 3.5 mg/kg body weight. In conclusion, these properties make AB1 (4) and AM2 (5) promising candidates for clinical use.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillus; Candida; Candidiasis; Cell Survival; Disease Models, Animal; Dose-Response Relationship, Drug; Erythrocytes; Female; Fibroblasts; Humans; Injections, Intravenous; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Molecular Structure; Polyethylene Glycols; Rhizopus; Solubility; Structure-Activity Relationship; Water

A set of crown ethyl acyl derivatives based on 18-crown-6 moiety was synthesized and evaluated for biological activity. In vitro antiproliferative profiling demonstrated significant activities against HBL-100, HeLa, SW1573 and WiDr human cell lines. The most active compound exhibited GI

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antineoplastic Agents; Candida albicans; Candidiasis; Cell Line, Tumor; Cell Proliferation; Crown Ethers; Drug Screening Assays, Antitumor; Humans; Neoplasms; Staphylococcal Infections; Staphylococcus aureus; Structure-Activity Relationship

Candida adherence is implicated in the pathogenesis of oral candidosis. Adhesion to buccal epithelial cells (BEC), germ tube (GT) formation, and relative cell surface hydrophobicity (CSH) are colonization attributes of candidal pathogenicity. Candida dubliniensis (C. dubliniensis) is allied with recurrent oral candidosis, which can be treated with nystatin, amphotericin B, ketoconazole, and fluconazole. Due to the diluent effect of saliva and the cleansing effect of the oral musculature in the oral cavity C. dubliniensis isolates undergo brief and sequential exposure to antifungal agents during therapy. Thus, in the present study, we evaluated the adhesion to BEC, GT formation, and the CSH of oral isolates of C. dubliniensis following brief and sequential exposure to nystatin, amphotericin B, ketoconazole, and fluconazole.. After determining the minimum inhibitory concentration (MIC) of the aforementioned drugs, 20 oral isolates of C. dubliniensis were briefly (1 h), and sequentially (10 days) exposed to subcidal concentrations of these drugs. Following drug removal, adhesion to BEC, GT formation, and CSH of these isolates were determined.. The percentage reduction of adhesion to BEC, GT formation, and CSH of the isolates following exposure to antifungal agents were as follows: nystatin: 53.55%, 33.98%, and 29.83% (P < 0.001); amphotericin B: 53.84%, 36.23%, and 28.97% (P < 0.001); ketoconazole: 37.43%, 20.51%, and 16.49% (P < 0.001); and fluconazole: 8.93% (P < 0.001), 1.6%, and 0.63% (P > 0.05).. Brief and sequential exposure of C. dubliniensis to antifungal agents would continue to wield an antifungal effect by altering its adhesion attributes, and elucidate possible pharmacodynamics by which antifungal agents might operate in modulating candidal adherence.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Epithelial Cells; Fluconazole; Humans; Ketoconazole; Microbial Sensitivity Tests; Mouth Mucosa; Nystatin

This research investigated the combination of polyethylene glycol with chitosan in point-of-care loaded sponges made by one or two lyophilizations for adjunctive local antifungal delivery in musculoskeletal wounds. Blended and control chitosan sponges were evaluated in vitro for antifungal release and activity, degradation, cytocompatibility, and characterized for spectroscopic, crystallinity, thermal, and morphologic material properties. In vivo biocompatibility and degradation of sponges were also evaluated in a rat intramuscular pouch model 4 and 10 days after implantation. Blended sponges released amphotericin B active against Candida albicans (>0.25 µg/mL) over 72 h and did not elicit cytotoxicity response of fibroblasts. Blended sponges exhibited decreases in surface roughness, decreased thermal decomposition temperatures, as well as small Fourier transform infrared spectroscopy and crystallinity differences, compared with chitosan-only sponges. Three of the four blended sponge formulations exhibited 31%-94% increases in in vitro degradation from the chitosan sponges after 10 days, but did not demonstrate the same increase in in vivo degradation. Low inflammatory in vivo tissue response to blended and chitosan-only sponges was similar over 10 days. These results demonstrated that adding polyethylene glycol to chitosan sponges does improve local antifungal release, cytocompatibility, and in vitro degradation, but does not increase in vivo degradation.

Topics: Amphotericin B; Animals; Candida albicans; Candidiasis; Chitosan; Drug Delivery Systems; Drug Evaluation, Preclinical; Male; Polyethylene Glycols; Rats; Rats, Sprague-Dawley

Recent publications suggest the distribution of Candida species causing candiduria may vary geographically, which has implications for the continued efficacy of antifungal therapy and emerging resistance.. To investigate the incidence of Candiduria at a university hospital in the UK. Further, to assess the distribution of species and the accompanying antifungal susceptibility profile, in order to monitor the clinical utility of current antifungal treatment guidelines for candiduria so that patients receive the best possible outcomes from the most up to date care.. Retrospective audit.. From 1st January 2005 to 31st October 2014, we retrospectively reviewed 37 538 positive urine cultures recorded in a computerized laboratory results database. Identification and susceptibility testing was performed using the VITEK® 2 fungal susceptibility card (bioMérieux, Marcy d'Etoile, France).. In total, 96 cultures were positive for Candida species, of which 69 (72%) were C.albicans, which translates to a prevalence of 2.6 per 1000 positive urine cultures. Candiduria was more common in younger patients, males and catheterized females. We report 94 and 73% of isolates of C.albicans and other non-C.albicans Candida species were susceptible to fluconazole. All isolates were susceptible to amphotericin B.. Our results add weight to the evidence supporting current European and North American guidelines recommending fluconazole or amphotericin B for treatment of candiduria, if antifungal treatment is clinically indicated.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Fluconazole; Flucytosine; Humans; Microbial Sensitivity Tests; Species Specificity; United Kingdom; Urinary Tract Infections

In this study, we evaluated the ability of the lipopeptide bacillomycin D and the antifungal drug amphotericin B as well as their combination, to inhibit Candida albicans biofilm formation and to accelerate keratinocyte cell migration.. The antibiofilm activity of bacillomycin D and its combination with amphotericin B was carried out by crystal violet colorimetric method. Our results have shown that, when combined together at low concentrations nontoxic to mammalian cells, corresponding to 1/32 MIC (0·39 μg ml(-1) ) and 1/4 MIC (0·06 μg ml(-1) ) for bacillomycin D and amphotericin B, respectively, a clear antibiofilm activity is manifested (95% inhibition of biofilm formation) along with a clear inhibition of germ tube formation. Moreover, the effect of both drugs on preformed biofilm of C. albicans strain was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The combination of the two antifungal compounds at 0·39 and 1 μg ml(-1) for bacillomycin D and amphotericin B, respectively, resulted in a clear enhancement of biofilm eradication compared to the results obtained with each drug alone. Furthermore, this combination was found to promote the closure of a gap produced in a monolayer of human keratinocytes.. Bacillomycin D and its combination with amphotericin B display impressive anti-biofilm and wound-healing activities.. Application of the lipopeptide bacillomycin D and the antifungal drug amphotericin B in medical devices may offer a promising alternative for topical treatment of Candida-associated infections in the setting of a wound.

Topics: Amphotericin B; Antifungal Agents; Antimicrobial Cationic Peptides; Biofilms; Candida albicans; Candidiasis; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Peptides; Wound Healing

Candida albicans is the common cause of some infectious diseases such as vaginal candidiasis or candidemia. Due to the emergence of drug resistant isolates of C. albicans, finding a new anti-Candida agent is a new strategy for current treatments. This study evaluated the anti-candidal activity of Satureja khuzistanica ethanol extract against clinical isolates of C. albicans. S. khuzistanica ethanol extract from aerial parts of plant at full flowering stage was evaluated against 30 clinical isolates and two ATCC reference strains of C. albicans by disc diffusion and micro-broth dilution assay. Also, in this study we evaluated the synergistic effects of amphotericin B, clotrimazole and ketoconazole with S. khuzistanica ethanol extract. The means of MIC and MFC of S. khuzistanica ethanol extract against clinical isolates were 299.4 and 722.6 (μg/mL), respectively. S. khuzistanica ethanol extract increased the anti-candidal effect of amphotericin B and ketoconazole, while it had no synergistic effect on clotrimazole against clinical isolates of C. albicans. Therefore, S. khuzistanica ethanol extract can be introduced as a new source of anti-candidal agent against clinical isolates of C. albicans.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Clotrimazole; Diabetes Complications; Drug Interactions; Female; Humans; Ketoconazole; Male; Microbial Sensitivity Tests; Plant Components, Aerial; Plant Extracts; Satureja; Vagina

To study the clinical characteristics, antibiotics sensitivity, outcome and risk factors of neonatal septicemia caused by Candida haemulonii.. A retrospective analysis was performed on clinical characteristics and antibiotics sensitivity after 8 cases of neonatal septicemia caused by Candida haemulonii were identified; each of these patients had at least one positive result of bacterial culture for Candida haemulonii.. The 8 cases born at gestational age of 178-260 d, weighing 835-2 055 g, developed the infection from May to July at 10-34 d after hospitalization. Among the 8 patients, 7 were cured, 1 died during hospitalization after the treatments were given up because of serious complications. The 8 patients with septicemia caused by Candida haemulonii had similar clinical chariacteristics to those of other neonatal candidemia, such as apnea, fever, abdominal distension, jaundice etc. They had abnormal auxiliary examination with increased C-reactive protein (CRP), declined platelet (PLT) count to different degrees. All of the 8 patients had peripherally inserted central catheter (PICC) and broad-spectrum antibiotics were applied. C. haemulonii as an emergent fungal pathogen had varying degrees of resistance to fluconazole, amphotericin B, itraconazole, or ketone, but was susceptible to voriconazole.. The characteristics of neonatal septicemia caused by Candida haemulonii were similar to those caused by other candida, and the main risk factors are the low birth weight, PICC, and usage of broad-spectrum antibiotics. It mainly occurred in May to July which is hot and humid season.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; C-Reactive Protein; Candida; Candidiasis; Fluconazole; Gestational Age; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intensive Care Units, Neonatal; Microbial Sensitivity Tests; Retrospective Studies; Sepsis

The echinocandins and liposomal amphotericin B are active against biofilm produced by echinocandin-susceptible Candida strains. However, few data have been reported on the production of biofilm by echinocandin-resistant isolates and their antifungal susceptibility. We studied the production of biofilm by fks mutant Candida strains and intrinsically echinocandin-resistant non-Candida isolates and the susceptibility of both entities to liposomal amphotericin B and echinocandins. We analyzed the production of biofilm by isolates from patients with fungemia (fks mutant Candida, n = 5; intrinsically echinocandin-resistant non-Candida, n = 12; and Candida wild type, n = 10). Biofilm formation was measured to classify strains according to biomass (crystal violet assay) and metabolic activity (XTT reduction assay). Preformed biofilms were tested against liposomal amphotericin B, caspofungin, micafungin, and anidulafungin. The sessile MIC was defined as the antifungal concentration yielding a 50% or 80% reduction in the metabolic activity of the biofilm compared to that of the growth control (SMIC50 and SMIC80, respectively). fks mutant Candida isolates formed biofilms in a fashion similar to that of Candida wild-type strains. The echinocandins had the highest activity against biofilms formed by wild-type Candida isolates, followed by fks mutant Candida isolates and non-Candida isolates. Liposomal amphotericin B had the highest activity against fks mutant Candida biofilms. The formation of biofilm by echinocandin-resistant strains was similar to that of wild-type strains, although resistance to echinocandins remained high.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Biofilms; Candida; Candidiasis; Caspofungin; Drug Resistance, Fungal; Echinocandins; Glucosyltransferases; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests

Chronic disseminated candidiasis (CDC) is a complication of Candida infection in immunocompromised patients, involving the liver and spleen, and rarely other organs. The aim of the study is to identify the best antifungal drug for hematologic immunocompromised patients with CDC.. In this multicentric retrospective study, the charts of 20 patients with CDC following cytotoxic agent protocols for hematological malignancies, diagnosed from 2003 to 2013, were analyzed. The response to systemic antifungal therapy within 90 days from CDC diagnosis and the possible delay in chemotherapy plan, due to the infection, were evaluated.. Six patients were treated with high-dose (HD; 5 mg/kg/daily) liposomal amphotericin B (L-AmB), whereas three received standard-dose (SD) L-AmB (3 mg/kg/daily). Azoles were given to six patients; the remaining five were treated with echinocandins. All patients treated with HD L-AmB (6/6-100 %) achieved complete resolution of CDC; one of them had to interrupt the chemotherapy program for the infection. In the SD L-AmB group, treatment failed in the 100 % of cases and one patient had to delay chemotherapy for the infection. Of the six patients who received azoles, two achieved complete resolution of the infection, four experienced treatment failure, and only three performed chemotherapy as planned. Echinocandins treatment resulted in complete resolution of the infection in 2/5 cases, partial response in 2/5 cases, and failure in one case. In this group, 3/5 patients completed chemotherapy as planned.. This study shows that HD L-AmB was particularly effective against CDC in hematologic patients, allowing most patients to continue cytotoxic agent program.

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Female; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Middle Aged; Retrospective Studies; Young Adult

In this study, our aim was to identify Candida species isolated from bloodstream infections and to determine their susceptibilities to various antifungal agents to demonstrate the local resistance profiles and to guide empirical treatment for clinicians.. Two hundred Candida isolates (95 Candida albicans, 105 non-albicans Candida strains) were included in the study. Candida species were identified by conventional, biochemical and molecular methods. Antifungal susceptibility tests for amphotericin B, fluconazole, voriconazole, posaconazole, caspofungin and anidulafungin were performed with broth microdilution method according to the Clinical and Laboratory Standards Institute M27-A3 document.. Of the 200 Candida strains, the most prevalent species were C. albicans (47.5 %), Candida glabrata (18.0 %) and Candida parapsilosis complex (14.0 %). All Candida species except for three (1.5 %) Candida kefyr strains were susceptible to amphotericin B. Only one (2.8 %) C. glabrata was resistant to fluconazole (MIC ≥ 64 μg/ml), and the others (97.2 %) exhibited dose-dependent susceptibility. All species, but C. glabrata strains, were susceptible to fluconazole. Resistance to voriconazole, posaconazole, caspofungin and anidulafungin was not detected in any strain.. Candida albicans were susceptible to all antifungal drugs. Three C. kefyr strains were resistant to amphotericin B. Only one C. glabrata was resistant to fluconazole. All the strains were susceptible to voriconazole, posaconazole, caspofungin and anidulafungin. In vitro antifungal susceptibility tests should be performed to select of appropriate and effective antifungal therapy, and monitor the development of resistance.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Candida; Candida albicans; Candidiasis; Caspofungin; Echinocandins; Fluconazole; Humans; Lipopeptides; Microbial Sensitivity Tests; Species Specificity; Triazoles; Voriconazole

Candida species are responsible for recurrent human infections, mostly in immunocompromised patients, due to their high vulnerability. Candida glabrata has a major role in systemic candidiasis and Amphotericin B (AmB), a polyene only used in hospitals, is frequently used to treat this disease. Lately, however, clinical evidences of Candida recurrent infections during these treatments are being described, probably due to biofilm (re)formation during this therapy. Thus, this work aims at inferring if C. glabrata biofilms are still being formed during AmB treatment. For that, C. glabrata biofilms were formed in the presence of AmB and analysed by dry weight. Matrix composition was analysed quantifying carbohydrates and, specifically, β-1,3 glucans. Results demonstrated that, although in a lesser extent, C. glabrata is able to develop biofilms in the presence of AmB, with a thick extracellular matrix, with an increase on carbohydrates, especially β-1,3 glucans. Therefore, it is confirmed that complex biofilms of C. glabrata can be formed during an AmB treatment.. This study shows new insights regarding recurrent candidiasis. The authors demonstrated that Amphotericin B did not totally prevent the development of biofilms during Candida glabrata's infection treatment and that the change in the biofilm matrices may have a high responsibility for the fail in the treatment of systemic candidiasis.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida glabrata; Candidiasis; Humans; Polyenes; Recurrence

The aim of this study was to evaluate the antifungal and cytotoxic activities of the oxidized form of amphotericin B (AmB-Ox) as well as to determine whether oxidation process of AmB is therapeutically beneficial in vitro. The antifungal activity was estimated against Candida albicans ATCC 10231 and Candida parasilosis ATCC 22019 by broth microdilution method according to the NCCLS M27-A2 standards. The in vitro cytotoxicity was evaluated using normal green monkey kidney cells (GMK) by MTT assay. The obtained results demonstrated that AmB-Ox possesses 16-fold decreased antifungal properties against the two Candida strains and 5-fold lower cytotoxic activity towards GMK cells in comparison with AmB. The therapeutic safety in vitro assessed by calculating the ratio between cytotoxicity (CC50 value) to antifungal activity (MIC value) showed that oxidation of AmB is a very unfavourable process in vitro, because leads to formation of derivative (AmB-Ox) that lost antifungal properties much more rapidly than cytotoxic activity. Thus, the process of the oxidation of AmB in vivo (if it occurs) can be also highly harmful for patient.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candida albicans; Candidiasis; Cell Line; Cell Survival; Chlorocebus aethiops; Humans; Kidney; Microbial Sensitivity Tests; Oxidation-Reduction

The effectiveness of anidulafungin versus liposomal amphotericin B (LAmB) for treating experimental Candida parapsilosis catheter-related infection by an antifungal-lock technique was assessed.. Two clinical strains of C. parapsilosis (CP12 and CP54) were studied. In vitro studies were used to determine the biofilm MICs (MBIC50 and MBIC90) by XTT reduction assay and LIVE/DEAD biofilm viability for anidulafungin and LAmB on 96-well microtitre polystyrene plates and silicone discs. An intravenous catheter was implanted in New Zealand white rabbits. Infection was induced by locking the catheter for 48 h with the inoculum. The 48 h antifungal-lock treatment groups included control, 3.3 mg/mL anidulafungin and 5.5 mg/mL LAmB.. Anidulafungin showed better in vitro activity than LAmB against C. parapsilosis growing in biofilm on silicone discs. MBIC90 of LAmB: CP12, >1024 mg/L; CP54, >1024 mg/L. MBIC90 of anidulafungin: CP12, 1 mg/L; CP54, 1 mg/L (P ≤ 0.05). Moreover, only anidulafungin (1 mg/L) showed >90% non-viable cells in the LIVE/DEAD biofilm viability assay on silicone discs. No differences were observed between the in vitro susceptibility of anidulafungin or LAmB when 96-well plates were used. Anidulafungin achieved significant reductions relative to LAmB in log10 cfu recovered from the catheter tips for both strains (P ≤ 0.05). Only anidulafungin achieved negative catheter tip cultures (CP12 63%, CP54 73%, P ≤ 0.05).. Silicone discs may be a more reliable substrate for the study of in vitro biofilm susceptibility of C. parapsilosis. Anidulafungin-lock therapy showed the highest activity for experimental catheter-related infection with C. parapsilosis.

Topics: Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Biofilms; Candida; Candidiasis; Catheter-Related Infections; Catheters, Indwelling; Echinocandins; Male; Microbial Sensitivity Tests; Rabbits; Silicones

Topics: Administration, Intravesical; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Device Removal; Female; Humans; Intraabdominal Infections; Intrauterine Devices; Multiple Organ Failure; Postoperative Care; Shock, Septic; Uterine Diseases

Candida spp. are the most common opportunistic mycosis worldwide. Although Candida albicans is the most common cause of urinary tract infections, the frequency of non-albicans Candida species is increasing with common use of antifungal in the prophylaxis and treatment. This may lead to difficulties in treatment. Antifungal tests should be applied with identification of species for effective treatment. In this study, identification of Candida species isolated from urine culture and investigation of susceptibility of these strains to amphotericin B, flucytosine, fluconazole, voriconazole was aimed. In this study, 58 Candida strains isolated from urine cultures at Osmaniye State Hospital between January 2012 and April 2013 were included. Urine culture and antifungal susceptibility tests were applied. Incidence rate of Candida spp. was determined as C. albicans (56.9%), Candida glabrata (20.6%), Candida tropicalis (10.3%), Candida parapsilosis (7%), Candida krusei (3.4%), Candida kefyr (1.8%). Most of the isolates were susceptible to amphotericin B, flucytosine, fluconazole, voriconazole. Twenty three (39.7%) Candida strains were isolated from internal medical branches and Intensive Care Unit and 12 (20.6%) from the Surgical Medical Branches. C. albicans and C. glabrata species were isolated most frequently as a candiduria factor in this hospital between January 2012 and April 2013. The analysis of antifungal susceptibility profile shows no significant resistance to antifungals.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Female; Fluconazole; Humans; Male; Middle Aged; Urinary Tract Infections; Young Adult

From a fungicidal screen, we identified 2-(2-oxo-morpholin-3-yl)-acetamide derivatives as fungicidal agents against Candida species, additionally characterized by antifungal activity against Aspergillus species. However, development of this series was hampered by low plasmatic stability. Introduction of a gem-dimethyl on the 6-position of the morpholin-2-one core led to considerable improvement in plasmatic stability while maintaining in vitro antifungal activity. Further optimization of the series resulted in the discovery of N-(biphenyl-3-ylmethyl)-2-(4-ethyl-6,6-dimethyl-2-oxomorpholin-3-yl)acetamide (87), which, in addition to fungicidal activity against Candida species, shows promising and broad antifungal in vitro activity against various fungi species, such as molds and dermatophytes. In vivo efficacy was also demonstrated in a murine model of systemic Candida albicans infection with a significant fungal load reduction in kidneys.

Topics: Acetamides; Animals; Antifungal Agents; Candida; Candidiasis; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Molecular Structure; Morpholines; Species Specificity; Structure-Activity Relationship; Substrate Specificity

Mould-active antifungal prophylaxis is increasingly used in patients at risk for invasive fungal disease. Between June 2011 and June 2012, one hundred patients with various haematological malignancies at risk for invasive fungal disease received primary antifungal prophylaxis with intravenous micafungin at a daily dosage of 50 mg during neutropenia. The median number of days on micafungin prophylaxis was 14 (range, 6-48 d). The incidence of proven and probable breakthrough invasive fungal diseases (bIFDs) was 6% and 3%, respectively. There were two bloodstream infections caused by yeasts or yeast-like fungi (Candida krusei, Trichosporon asahii) in two patients during the neutropenic phase after allogeneic haematopoietic stem cell transplantation. Four proven bIFDs caused by non-Aspergillus moulds and three cases of probable pulmonary bIFDs were documented during the neutropenic phase after induction/consolidation chemotherapy for acute leukaemia. Colonisation with Candida spp. was documented in 51% of the patients with none of the isolates being in vitro micafungin resistant. Compared to a historical control, receiving primary prophylaxis with posaconazole micafungin is at least as effective in preventing IFD. In both cohorts, bIFDs were exclusively caused by emerging pathogens with a highly preserved in vitro sensitivity to amphotericin B.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Administration Schedule; Echinocandins; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Injections, Intravenous; Lipopeptides; Male; Micafungin; Middle Aged; Retrospective Studies; Transplantation, Homologous; Triazoles; Trichosporon; Trichosporonosis

To evaluate the antifungal activity of amphotericin B (AmB) in a mouse model of systemic candidiasis following administration of a novel oral AmB formulation (iCo-010) that has been pre-exposed to tropical temperatures.. Amphotericin B (AmB) was prepared as a 5 mg/mL dispersion in a mixture of Peceol, Gelucire 44/14 and VitE-TPGS 2,3 (iCo-010). The formulation was protected from light and incubated in a sealed container at 43 °C for 60 days. Mice infected with Candida albicans were treated with either iCo-010 formulation pre-incubated at 43 °C for 60 days or freshly prepared iCo-010 formulation at doses of 5, 10 and 20 mg/kg once daily for five consecutive days. Single intravenous 5 mg/kg dose of AmBisome® was used as a positive control group. Seven days following the last dose, the kidney, liver, spleen, lung, heart and brain were removed and the number of colony forming units (CFUs) was determined as a measure of tissue fungal load. In addition, the concentration of AmB within each tissue was determined using high performance liquid chromatography (HPLC).. There were no significant differences in the reduction of CFUs and the concentration of AmB recovered in all organs at all iCo-010 doses tested between the freshly prepared iCo-010 formulation compared to the formulation that was incubated at 43 °C for 60 days.. A novel oral AmB formulation, iCo-010, incubated at 43 °C for 60 days to simulate the exposure of the formulation to tropical temperatures remained highly effective against murine systemic candidiasis.

Topics: Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Chromatography, High Pressure Liquid; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Stability; Drug Storage; Excipients; Female; Mice; Mice, Inbred BALB C; Temperature; Tissue Distribution; Tropical Climate

Minor species of the Candida albicans complex may cause overestimation of the epidemiology of C. albicans, and misidentifications could mask their implication in human pathology. Authors determined the occurrence of minor species of the C. albicans complex (C. africana, C. dubliniensis and C. stellatoidea) among Yaoundé HIV-infected patients, Cameroon. Stool, vaginal discharge, urine and oropharyngeal samples were analysed by mycological diagnosis. Isolates were identified by conventional methods and mass spectrometry (MS; carried out by the matrix-assisted laser desorption-ionisation time-of-flight MS protocol). Candida albicans isolates were thereafter submitted to the PCR amplification of the Hwp1 gene. The susceptibility of isolates to antifungal drugs was tested using the Clinical and Laboratory Standards Institute M27-A3 protocol. From 115 C. albicans obtained isolates, neither C. dubliniensis nor C. stellatoidea was observed; two strains of C. africana (422PV and 448PV) were identified by PCR electrophoretic profiles at 700 bp. These two C. africana strains were vaginal isolates. The isolate 448PV was resistant to ketoconazole at the minimal inhibitory concentration of 2 μg ml(-1), and showed reduced susceptibility to amphotericin B at 1 μg ml(-1). This first report on C. africana occurrence in Cameroon brings clues for the understanding of the global epidemiology of this yeast as well as that of minor species of the C. albicans complex.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cameroon; Candida; Candida albicans; Candidiasis; Drug Resistance, Fungal; Female; Gene Expression Regulation, Fungal; Humans; Male; Middle Aged; Polymerase Chain Reaction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Urine; Vagina; Young Adult

Mucosal biofilm-related fungal infections are very common, and the incidence of recurrent oral and vulvovaginal candidiasis is significant. As resistance to azoles (the preferred treatment) is occurring, we aimed at identifying compounds that increase the activity of miconazole against Candida albicans biofilms. We screened 1,600 compounds of a drug-repositioning library in combination with a subinhibitory concentration of miconazole. Synergy between the best identified potentiators and miconazole was characterized by checkerboard analyses and fractional inhibitory concentration indices. Hexachlorophene, pyrvinium pamoate, and artesunate act synergistically with miconazole in affecting C. albicans biofilms. Synergy was most pronounced for artesunate and structural homologues thereof. No synergistic effect could be observed between artesunate and fluconazole, caspofungin, or amphotericin B. Our data reveal enhancement of the antibiofilm activity of miconazole by artesunate, pointing to potential combination therapy consisting of miconazole and artesunate to treat C. albicans biofilm-related infections.

Topics: Amphotericin B; Antifungal Agents; Artemisinins; Artesunate; Biofilms; Candida albicans; Candidiasis; Caspofungin; Drug Synergism; Echinocandins; Fluconazole; Hexachlorophene; Lipopeptides; Miconazole; Microbial Sensitivity Tests; Pyrvinium Compounds; Reactive Oxygen Species

Switching between two cell types in fungi is called phenotypic switching, and it is commonly observed in pathogenic yeast. Candida lusitaniae undergoes antifungal resistance-associated phenotypic switching and results in three colony colors: light brown, brown and dark brown. In this study, we included C. lusitaniae as control. This study had two objectives. First, we wanted to evaluate whether also a prevalent human pathogen C. guilliermondii can undergo phenotypic switching. Second, our aim was to determine whether switching can change yeasts susceptibility to antifungals. Yeast suspension (1 × 10(3)-5 × 10(3) c.f.u./ml) was plated on the YPD medium containing 1 mM CuSO4. Colonies exhibiting the original and variant phenotypes were counted and converted to percentage of the population. Minimum inhibitory concentrations of amphotericin B, formic acid and acetic acid for the cells from random colonies of the different phenotypes were determined by microdilution method. After 5 days of incubation, C. guilliermondii switched spontaneously and reversibly among two phenotypes distinguishable on CuSO4 containing agar, white and dark brown. Phenotypes occurred with greater frequency (10(-1)-10(-2)) than spontaneous mutations and were reversible, fulfilling the two phenotypic switching criteria. The study showed that phenotypic switching was associated with filamentation and affected antifungal resistance. Resistance to amphotericin B increased tenfold and was associated with C. lusitaniae dark brown phenotype. C. guilliermondii colonies with brown phenotype displayed 20 and 2 times higher resistance to amphotericin B and acetic acid, respectively.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Humans; Hyphae; Microbial Sensitivity Tests; Phenotype

Current guidelines for treatment of Candida osteoarticular infections (COAIs) recommend a prolonged course of antifungal therapy (AFT) of 6-12 months. Based upon strategies developed at the Hospital for Special Surgery (HSS), we hypothesized that the duration of antifungal therapy may be substantially reduced for management of COAI.. This was a retrospective chart review of cases of COAI treated at the HSS for the past 14 years. COAI was documented by open biopsy and direct culture in all cases. The mean (95% confidence interval, CI) duration of documented follow-up was 39 (16-61) months.. Among the 23 cases of COAI, the median age was 62 years (range 22-83 years) with 61% having no underlying condition. Orthopedic appliances, including joint prostheses and fracture hardware, were present in 74% of cases. All patients had COAI as the first proven site of candidiasis. Candida albicans and Candida parapsilosis were the most common species. Hip, knee, foot, and ankle were the most common sites. All patients received aggressive surgical intervention followed by AFT administered for a mean (95% CI) duration of 45 (38-83) days. Systemic AFT consisted principally of fluconazole alone (65%) or in combination with other agents (26%). Adjunctive intraoperative amphotericin B irrigation was used in 35%. Among eight cases of CAOI that required placement of a new prosthetic joint, all were successfully treated. There were no microbiologic failures.. Candida osteoarticular infections may be successfully treated with substantially limited durations of AFT when combined with a thorough surgical approach.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candidiasis; Combined Modality Therapy; Deoxycholic Acid; Drug Combinations; Female; Humans; Male; Middle Aged; Orthopedic Procedures; Osteomyelitis; Prosthesis-Related Infections; Retrospective Studies; Young Adult

Candida albicans persisters constitute a small subpopulation of biofilm cells and play a major role in recalcitrant chronic candidiasis; however, the mechanism underlying persister formation remains unclear. Persisters are often described as dormant, multidrug-tolerant, nongrowing cells. Persister cells are difficult to isolate and study not only due to their low levels in C. albicans biofilms but also due to their transient, reversible phenotype. In this study, we tried to induce persister formation by inducing C. albicans cells into a dormant state. C. albicans cells were pretreated with 5-fluorocytosine (planktonic cells, 0.8 μg ml(-1); biofilm cells, 1 μg ml(-1)) for 6 h at 37°C, which inhibits nucleic acid and protein synthesis. Biofilms and planktonic cultures of eight C. albicans strains were surveyed for persisters after amphotericin B treatment (100 μg ml(-1) for 24 h) and CFU assay. None of the planktonic cultures, with or without 5-fluorocytosine pretreatment, contained persisters. Persister cells were found in biofilms of all tested C. albicans strains, representing approximately 0.01 to 1.93% of the total population. However, the persister levels were not significantly increased in C. albicans biofilms pretreated with 5-fluorocytosine. These results suggest that inhibition of nucleic acid synthesis did not seem to increase the formation of amphotericin B-tolerant persisters in C. albicans biofilms.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Flucytosine; Microbial Sensitivity Tests; Nucleic Acids

Candida species has become the seventh most frequent causal microorganisms of nosocomial sepsis. Prematurity and low birth weights are strongly associated with the development of neonatal nosocomial bloodstream infections. Candida albicans has been the species most often associated with neonatal infections, but recently, there has been a changing pattern in the isolates recovered from neonates with invasive candidiasis, which poses resistance to the existing class of azoles such as fluconazole antifungals along with cross resistance to newer triazoles, which results in a therapeutic challenge in invasive fungal infections causing high incidence of mortality. Candida species was isolated from blood of neonates and children younger than 15 years admitted to hospital and susceptible for Candida-induced sepsis. Polymerase chain reaction-based identification and confirmation of individual Candida species were done using DNA sequencing. Antibiotic susceptibility assay and resistance pattern for fluconazole, voriconazole, and amphotericin were done for all the isolates. Furthermore, the change in free radical, cytokine release, and nitric oxide synthase expression and nitric oxide release from polymorphonuclear leukocytes isolated from control and pediatric sepsis cases were also performed. The present study probably for the first time reports the change in increasing incidence of nonalbicans Candida-induced sepsis in neonates and children admitted to the intensive care unit of hospital, and current antibiotics load posing resistance for antifungal treatment strategy and provide serious threats in future treatment. The increase in free radicals in polymorphonuclear leukocytes and increase in expression of nitric oxide synthase expression and nitric oxide release in Candida-infected pediatric sepsis cases underlie the role of host factor in dissemination and invasiveness of infection from exogenous sources and pathogenesis of systemic inflammation during sepsis.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candida; Candidemia; Candidiasis; Child; Child, Preschool; Cross Infection; Cytokines; Female; Fluconazole; Free Radicals; Humans; Incidence; India; Infant; Infant, Newborn; Intensive Care Units; Interleukin-10; Interleukin-1beta; Male; Microbial Sensitivity Tests; Nitric Oxide; Nitric Oxide Synthase; Sepsis; Tumor Necrosis Factor-alpha; Voriconazole

The increasing importance of clinical isolates of Candida species and emerging resistance of Candida species to current synthetic antifungal agents have stimulated the search for safer and more effective alternative drugs from natural sources. This study was directed towards exploring the antimycotic potential of a diterpenoid compound taxodone isolated from Metasequoia glyptostroboides against pathogenic isolates of Candida species.. Antimycotic efficacy of taxodone was evaluated by disc diffusion assay, determination of minimum inhibitory (MIC) and minimum fungicidal (MFC) concentrations, and cell viability assay. To confirm a partial antimycotic mode of action of taxodone, the efficacy of taxodone was determined by measuring the release of 260 nm absorbing materials from the selected Candida species as compared to control.. The taxodone at the concentration of 400 μg/disc displayed potential antimycotic effect against the tested clinical and pathogenic isolates of Candida species as diameters of zones of inhibitions, which were found in the range of 11 ± 0.0 to 12.6 ± 0.5mm. The MIC and MFC values of taxodone against the tested clinical isolates were found in the range of 250 to 1000 and 500 to 2000μ g/mL, respectively. On the other hand, the MIC and MFC values of positive control (amphotericin B) against the tested Candida isolates were found in the range of 62.5 to 250 and 500 to 2000 μg/mL. On the viable counts of the tested fungal isolates, the taxodone exerted significant antimycotic effect. Elaborative study of partial mode of action conducted onto the release of 260nm materials (DNA and RNA) revealed potential detrimental effect of taxodone on the membrane integrity of the tested pathogens at MIC concentration.. With respect to the antimycotic effect of taxodone against pathogenic and clinical isolates of Candida species, it might be confirmed that bioactive compound taxodone present in M. glyptostroboides holds therapeutic value of medicinal significance.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cupressaceae; Diterpenes; Humans; Microbial Sensitivity Tests

Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis.

Topics: Adult; Age Factors; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Cohort Studies; Cross Infection; Echinocandins; Endocarditis; Female; Hospital Mortality; Humans; Male; Middle Aged; Prospective Studies; Risk Factors

The increase in drug resistance to current antifungal drugs brings enormous challenges to the management of Candida infection. Therefore, there is a continuous need for the discovery of new antimicrobial agents that are effective against Candida infections especially from natural source especially from medical plants. The present investigation describes the synergistic anticandidal activity of two asarones (∞ and β) purified from Acorus calamus in combination with three clinically used antifungal drugs (fluconazole, clotrimazole, and amphotericin B). The synergistic anticandidal activities of asarones and drugs were assessed using the checkerboard microdilution and time-kill assays. The results of the present study showed that the combined effects of asarones and drugs principally recorded substantial synergistic activity (fractional inhibitory concentration index (FICI) <0.5). Time-kill study by combination of the minimal inhibitory concentration (MIC) of asarones and drugs (1:1) recorded that the growth of the Candida species was significantly arrested between 0 and 2 h and almost completely attenuated between 2 and 6 h of treatment. These findings have potential implications in adjourning the development of resistance as the anticandidal activity is achieved with lower concentrations of asarones and drugs. The combination of asarones and drugs also significantly inhibit the biofilm formation by Candida species, and this would also help to fight against drug resistance because biofilms formed by Candida species are ubiquitous in nature and are characterized by their recalcitrance toward antimicrobial treatment. The in vitro synergistic activity of asarones and drugs against pathogenic Candida species is reported here for the first time.

Topics: Acorus; Allylbenzene Derivatives; Amphotericin B; Anisoles; Antifungal Agents; Azoles; Biofilms; Candida albicans; Candidiasis; Drug Synergism; Humans; Microbial Sensitivity Tests

The fluorinated glucocorticoid betamethasone stimulated both the extracellular phospholipase production and hypha formation of the opportunistic human pathogen Candida albicans and also decreased the efficiency of the polyene antimycotics amphotericin B and nystatin against C. albicans in a dose-dependent manner. Importantly, betamethasone increased synergistically the anti-Candida activity of the oxidative stress generating agent menadione, which may be exploited in future combination therapies to prevent or cure C. albicans infections, in the field of dermatology.

Topics: Amphotericin B; Antifungal Agents; Betamethasone; Candida albicans; Candidiasis; Drug Synergism; Drug Therapy, Combination; Humans; Hyphae; Microbial Sensitivity Tests; Nystatin; Oxidative Stress; Vitamin K 3

We herein report the case of a 72-year-old man with endocarditis of the aortic valve who underwent urgent aortic valve replacement 36 hours after admission due to an aggravation of aortic valve regurgitation. Postoperative cultures of the blood and site of valve vegetation identified Candida parapsilosis as a pathogen. Antifungal therapy with amphotericin B and fluconazole was initiated after surgical treatment. Thereafter, the patient displayed a favorable clinical course. Candida parapsilosis endocarditis involving the native valves is extremely rare and associated with a very high mortality rate. Prompt surgical treatment and the aggressive use of antifungal agents are required to save the patient's life.

Topics: Aged; Amphotericin B; Antifungal Agents; Aortic Valve; Candida; Candidiasis; Endocarditis; Fluconazole; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Treatment Outcome

Candida glabrata is currently ranked as the second most frequently isolated aetiological agent of human fungal infections, next only to Candida albicans. In comparison with C. albicans, C. glabrata shows lower susceptibility to azoles, the most common agents used in treatment of fungal infections. Interestingly, the mechanisms of resistance to azole agents in C. albicans have been much better investigated than those in C. glabrata. The aim of the presented study was to determine the mechanisms of resistance to azoles in 81 C. glabrata clinical isolates from three different hospitals in Poland. The investigation was carried out with a Sensititre Yeast One test and revealed that 18 strains were resistant to fluconazole, and 15 were cross-resistant to all other azoles tested (voriconazole, posaconazole and itraconazole). One isolate resistant to fluconazole was cross-resistant to voriconazole, and resistance to voriconazole only was observed in six other isolates. All strains were found to be susceptible to echinocandins and amphotericin B, and five were classified as resistant to 5-fluorocytosine. The sequence of the ERG11 gene encoding lanosterol 14-α demethylase (the molecular target of azoles) of 41 isolates, including all strains resistant to fluconazole and three resistant only to voriconazole, was determined, and no amino acid substitutions were found. Real-time PCR studies revealed that 13 of 15 azole-resistant strains showed upregulation of the CDR1 gene encoding the efflux pump. No upregulation of expression of the CDR2 or ERG11 gene was observed.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida glabrata; Candidiasis; Cytochrome P-450 Enzyme System; Drug Resistance, Fungal; Echinocandins; Fungal Proteins; Gene Expression Profiling; Hospitals; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Poland; Polymerase Chain Reaction; Sequence Analysis, DNA

To compare the in vitro activity of topical amphotericin B (AMB), natamycin, voriconazole, and fluconazole against human corneal isolates of Candida sp. for guidance in the treatment of Candida keratitis.. Sixty-eight Candida isolates (37 albicans and 31 non-albicans isolates) recovered from corneal scrapings submitted to rule out microbial keratitis, during the years 2005 to 2011, at the Bascom Palmer Eye Institute, were examined in this study. Corneal isolates were cultured on fungal agars for 48 hours. Each yeast isolate was dispensed into 4 microtiter wells, each containing 100 mL of commercial (natamycin 5%) or compounded (AMB 0.15%, voriconazole 1%, and fluconazole 0.2%) antifungal medications. A comparison of growth patterns was conducted.. One hundred percent of the samples showed growth inhibition after treatment exposure with AMB or natamycin. The isolates treated with voriconazole demonstrated an 85% inhibition rate overall, with the Candida albicans samples showing a 77% inhibition rate and the non-albicans sp. a 93% inhibition rate. In the fluconazole group, there was only a 19.6% inhibition rate noted, with a 7.7% inhibition rate observed in the C. albicans group versus a 30% inhibition rate in the non-albicans group.. AMB 0.2% and natamycin 5% have equal effectiveness and full inhibition against Candida keratitis isolates. Fluconazole 0.2% is not the drug of choice in both C. albicans and non-albicans keratitis. Voriconazole 1% may need a stronger concentration for higher effectiveness, but potentially may be helpful as a second agent in the treatment of Candida keratitis.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candidiasis; Corneal Ulcer; Eye Infections, Fungal; Fluconazole; Humans; Microbial Sensitivity Tests; Natamycin; Voriconazole

Candida albicans is a common cause of a variety of superficial and invasive disseminated infections the majority of which are associated with biofilm growth on implanted devices. The aim of the study is to evaluate the activity of amphotericin B and voriconazole against the biofilm and the biofilm-dispersed cells of Candida albicans using a newly developed in vitro pharmacokinetic model which simulates the clinical situation when the antifungal agents are administered intermittently.. RPMI medium containing 1-5 X 10(6) CFU/ml of C. albicans was continuously delivered to the device at 30 ml/h for 2 hours. The planktonic cells were removed and biofilms on the catheter were kept under continuous flow of RPMI medium at 10 ml/h. Five doses of amphotericin B or voriconazole were delivered to 2, 5 and 10 day-old biofilms at initial concentrations (2 and 3 μg/ml respectively) that were exponentially diluted. Dispersed cells in effluents from the device were counted and the adherent cells on the catheter were evaluated after 48 h of the last dose.. The minimum inhibitory concentration of voriconazole and amphotericin B against the tested isolate was 0.0325 and 0.25 μg/ml respectively. Amphotericin B significantly reduced the dispersion of C. albicans cells from the biofilm. The log10 reduction in the dispersed cells was 2.54-3.54, 2.30-3.55, and 1.94-2.50 following addition of 5 doses of amphotericin B to 2-, 5- and 10-day old biofilms respectively. The number of the viable cells within the biofilm was reduced by 18 (±7.63), 5 and 4% following addition of the 5 doses of amphotericin B to the biofilms respectively. Voriconazole showed no significant effect on the viability of C. albicans within the biofilm.. Both antifungal agents failed to eradicate C. albicans biofilm or stop cell dispersion from them and the resistance progressed with maturation of the biofilm. These findings go along with the need for removal of devices in spite of antifungal therapy in patients with device-related infection. This is the first study which investigates the effects of antifungal agents on the biofilm and biofilm-dispersion of C. albicans in an in vitro pharmacokinetic biofilm model.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Humans; Microbial Sensitivity Tests; Voriconazole

Topics: Adult; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Combined Modality Therapy; Conjunctivitis, Allergic; Corneal Ulcer; Drug Therapy, Combination; Eye Infections, Bacterial; Eye Infections, Fungal; Female; Humans; Keratoplasty, Penetrating; Male; Natamycin; Staphylococcal Infections; Staphylococcus aureus

Candida albicans biofilms contain a subpopulation whose members are defined as persisters, displaying great tolerance of fungicides. To directly observe such persisters, an effective method using green fluorescent protein (GFP) strain labeling by mutation of the gene encoding glyceraldehyde-3-phosphate dehydrogenase (TDH3), combined with propidium iodide (PI) staining, was established. Amphotericin B-tolerant persisters harbor the characteristics of both GFP positivity [GFP (+)] and propidium iodide (PI) negativity [PI (-)], which are easily visualized using a fluorescence microscope and measured by flow cytometry.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Drug Resistance, Multiple, Fungal; Flow Cytometry; Fluorescent Dyes; Glyceraldehyde-3-Phosphate Dehydrogenases; Green Fluorescent Proteins; Humans; Microbial Sensitivity Tests; Microscopy, Fluorescence; Propidium

The objective of this study was to characterize the underlying molecular mechanisms in consecutive clinical Candida albicans isolates from a single patient displaying stepwise-acquired multidrug resistance.. Nine clinical isolates (P-1 to P-9) were susceptibility tested by EUCAST EDef 7.2 and Etest. P-4, P-5, P-7, P-8 and P-9 were available for further studies. Relatedness was evaluated by MLST. Additional genes were analysed by sequencing (including FKS1, ERG11, ERG2 and TAC1) and gene expression by quantitative PCR (CDR1, CDR2 and ERG11). UV-spectrophotometry and GC-MS were used for sterol analyses. In vivo virulence was determined in the insect model Galleria mellonella and evaluated by log-rank Mantel-Cox tests.. P-1 + P-2 were susceptible, P-3 + P-4 fluconazole resistant, P-5 pan-azole resistant, P-6 + P-7 pan-azole and echinocandin resistant and P-8 + P-9 MDR. MLST supported genetic relatedness among clinical isolates. P-4 harboured four changes in Erg11 (E266D, G307S, G450E and V488I), increased expression of ERG11 and CDR2 and a change in Tac1 (R688Q). P-5, P-7, P-8 and P-9 had an additional change in Erg11 (A61E), increased expression of CDR1, CDR2 and ERG11 (except for P-7) and a different amino acid change in Tac1 (R673L). Echinocandin-resistant isolates harboured the Fks1 S645P alteration. Polyene-resistant P-8 + P-9 lacked ergosterol and harboured a frameshift mutation in ERG2 (F105SfsX23). Virulence was attenuated (but equivalent) in the clinical isolates, but higher than in the azole- and echinocandin-resistant unrelated control strain.. C. albicans demonstrates a diverse capacity to adapt to antifungal exposure. Potentially novel resistance-inducing mutations in TAC1, ERG11 and ERG2 require independent validation.

Topics: Aged; Amphotericin B; Animals; Antifungal Agents; Azoles; Candida albicans; Candidiasis; DNA, Fungal; Drug Resistance, Multiple, Fungal; Echinocandins; Genotype; Humans; Lepidoptera; Male; Microbial Sensitivity Tests; Multilocus Sequence Typing; Mutation; Sequence Analysis, DNA; Survival Analysis; Virulence

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Humans; Urea

Drugs that act more promiscuously provide fewer routes for the emergence of resistant mutants. This benefit, however, often comes at the cost of serious off-target and dose-limiting toxicities. The classic example is the antifungal amphotericin B (AmB), which has evaded resistance for more than half a century. We report markedly less toxic amphotericins that nevertheless evade resistance. They are scalably accessed in just three steps from the natural product, and they bind their target (the fungal sterol ergosterol) with far greater selectivity than AmB. Hence, they are less toxic and far more effective in a mouse model of systemic candidiasis. To our surprise, exhaustive efforts to select for mutants resistant to these more selective compounds revealed that they are just as impervious to resistance as AmB. Thus, highly selective cytocidal action and the evasion of resistance are not mutually exclusive, suggesting practical routes to the discovery of less toxic, resistance-evasive therapies.

Topics: Amphotericin B; Animals; Antifungal Agents; Binding Sites; Candida; Candidiasis; Cell Line; Cell Survival; Drug Resistance, Fungal; Epithelial Cells; Ergosterol; Humans; Mice; Microbial Viability; Structure-Activity Relationship; Survival Analysis; Urea

Colonization of patients occurs before development into invasive candidiasis. There is a need to determine the incidences of Candida colonization and infection in SICU patients, and evaluate the usefulness of beta-D-glucan (BDG) assay in diagnosing invasive candidiasis when patients are colonized.. Clinical data and fungal surveillance cultures in 28 patients were recorded from November 2010, and January to February 2011. Susceptibilities of Candida isolates to fluconazole, voriconazole, amphotericin B, micafungin, caspofungin and anidulafungin were tested via Etest. The utilities of BDG, Candida score and colonization index for candidiasis diagnosis were compared via ROC.. 30 BDG assays were performed in 28 patients. Four assay cases had concurrent colonization and infection; 23 had concurrent colonization and no infection; three had no concurrent colonization and infection. Of 136 surveillance swabs, 52 (38.24 %) were positive for Candida spp, with C. albicans being the commonest. Azole resistance was detected in C. albicans (7 %). C. glabrata and C. tropicalis were, respectively, 100 and 7 % SDD to fluconazole. All 3 tests showed high sensitivity of 75-100 % but poor specificity ranging 15.38-38.46 %. BDG performed the best (AUC of 0.89).. Despite that positive BDG is common in surgical patients with Candida spp colonization, BDG performed the best when compared to CI and CS.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Anidulafungin; Antifungal Agents; beta-Glucans; Candida; Candida albicans; Candida glabrata; Candidiasis; Candidiasis, Invasive; Carrier State; Caspofungin; Critical Care; Echinocandins; Female; Fluconazole; Humans; Incidence; Intensive Care Units; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Sensitivity and Specificity; Singapore; Tertiary Care Centers; Voriconazole

The purposes of this study were to investigate the enzymatic activity of different Candida species and their antifungal susceptibility patterns. The study involved a total of 83 isolates of Candida from the genital tract of the female Camelus dromedarius. After species identification, the isolates were analysed for the production/activity of phospholipase, proteinase and haemolysin. In addition, the agar disc diffusion method was performed on the basis of CLSI guidelines M44-A2 protocol for antifungal susceptibility testing. All the isolates were able to produce phospholipase, proteinase and haemolysin. A total of 35.48%, 87.09% and 64.51% of C. albicans isolates exhibited very high phospholipase, proteinase and haemolytic activities, respectively, whereas very high phospholipase, proteinase and haemolytic activities were determined in 5.76%, 23.07% and 45.16% of non-C. albicans isolates respectively. Overall, 61 (73.5%) of Candida isolates were susceptible to fluconazole, 70 (84.3%) susceptible to clotrimazole, 82 (98.8%) susceptible to voriconazole, 76 (91.6%) susceptible to itraconazole, 75 (90.4%) susceptible to ketoconazole, 83 (100%) susceptible to amphotericin B, 81 (97.6%) susceptible to nystatin and 36 (43.4%) susceptible to flucytosine. Candida isolates showed higher haemolytic activity than that of other secreted hydrolases among vaginal Candida species. In addition, amphotericin B was the most in vitro effective antifungal drug and flucytosine had the poorest activity under such conditions.

Topics: Amphotericin B; Animals; Antifungal Agents; Camelus; Candida; Candida albicans; Candidiasis; Female; Flucytosine; Fungal Proteins; Hemolysin Proteins; Microbial Sensitivity Tests; Nystatin; Peptide Hydrolases; Phospholipases; Reproductive Tract Infections; Virulence Factors

Candida bracarensis is an uncommon Candida species found during an epidemiological study of candidiasis performed in Braga, Portugal. Initially, it was identified as C. glabrata, but recently detailed analyses pointed out their differences. So, little information is still available about C. bracarensis virulence factors and antifungal susceptibilities. Therefore, the main goal of this work is to evaluate the ability of C. bracarensis to form biofilms, to produce hydrolytic enzymes (proteases, phospholipases and hemolysins), as well as its susceptibility to amphotericin B and fluconazole. It was shown, for the first time, that all C. bracarensis strains were able to form biofilms and display proteinase and hemolytic activities. Moreover, although planktonic cells presented antifungal susceptibility, amphotericin B and fluconazole were unable to inhibit biofilm formation and eradicate pre-formed biofilms. Due to the propensity of C. bracarensis to display antifungal resistance and virulence attributes, the control of these emerging pathogens is recommended.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida; Candidiasis; Drug Resistance, Fungal; Fluconazole; Hemolysis; Humans; Hydrolases; Mycotoxins; Virulence Factors

Candida tropicalis has emerged as one of the most prevalent fungal pathogens, and its ability to form biofilms has been considered one of the most important virulence factors, since they represent high tolerance to antifungal agents. However, the mechanisms of biofilm resistance to antifungal agents remain poorly understood. Thus, the main goal of this study was to infer about the ability of amphotericin B (AMB) to control and combat C. tropicalis biofilms. Additionally, it was also intended to determine the influence of matrix components in biofilm resistance. AMB was unable to totally prevent biofilm formation and to eradicate C. tropicalis preformed biofilms. Moreover, AMB led to a significant increase of the biofilm production due to an augment of the total protein and carbohydrate contents of the matrix. The C. tropicalis biofilm matrix assumes an important role on its resistance to AMB.

Topics: Amphotericin B; Biofilms; Candida tropicalis; Candidiasis; Drug Resistance, Fungal; Humans

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Humans; Urea

To evaluate the outcomes of intravitreal liposomal amphotericin B (L-AmB) for treatment of endogenous candida endophthalmitis.. Medical records of four patients with endogenous candida endophthalmitis treated with intravitreal L-AmB injection alone or combined with vitrectomy were reviewed.. Endogenous candida endophthalmitis developed in two patients after gastrointestinal surgery, in one patient with sepsis, and in one patient undergoing systemic chemotherapy for metastatic breast cancer. Three eyes of two patients exhibited toxic uveitis following repetitive intravitreal injection of amphotericin B deoxycholate (AmB-D, 10 μg/0.1 ml). The other patients had general health issues that restricted the use of AmB-D due to the potential risk of systemic toxicity. Seven eyes underwent intravitreal injection of L-AmB (10 μg/0.1 ml) with or without vitrectomy. In these patients, intraocular inflammation and vitreous opacities resolved, and chorioretinal infiltrates evolved into fibrotic scars. Visual acuity improved and stabilized in all eyes during the follow-up period.. Intravitreal L-AmB seems to be well tolerated and effective in the treatment of endogenous candida endophthalmitis, and may be a reasonable alternative for patients who cannot endure the side effects or toxicity associated with conventional AmB-D therapy.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Combined Modality Therapy; Endophthalmitis; Eye Infections, Fungal; Female; Humans; Intravitreal Injections; Male; Middle Aged; Visual Acuity; Vitrectomy; Vitreous Body

The aim of this work is to study the micelle systems of amphotericin B (AmB) and surfactant sodium deoxycholate (NaDC) as possible formulations to treat brain fungal infections. Fungizone(®) and Ambisome(®) were used as AmB references. The particle size, aggregation state, toxicity and efficacy of AmB:NaDC micelles were studied with increasing proportions of NaDC. Differences in the size and aggregation state of the reference formulations and micellar NaDC formulations might explain the differences in their distribution and therefore in their toxicity and efficacy. AmB:NaDC 1:0.8 and 1:1.5 nano-sized micelle systems showed a poly-aggregated form of AmB and small mean particle size (450-750 nm). The AmB:NaDC 1:0.8 and AmB:NaDC 1:1.5 micelle systems studied showed an 8-fold lower toxicity than Fungizone(®). Efficacy was examined in a murine candidiasis model by determining the survival rate and tissue burden reduction in kidneys and brain. The AmB:NaDC 1:1.5 micellar system at 5mg/kg of AmB and the highest amount of NaDC (7.5 mg/kg) presented a good survival rate, and induced a major clearance of brain infection. The new AmB:NaDC 1:1.5 nano-sized micelle system is a promising formulation with a good efficacy/toxicity ratio, which can be attributed to its particle size, AmB aggregation state and NaDC content.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Candida albicans; Candidiasis; Chemistry, Pharmaceutical; Deoxycholic Acid; Erythrocytes; Kidney; Male; Mice; Micelles; Particle Size; Surface-Active Agents

In vitro combination testing with broth microdilution chequerboard (CHEQ) method is widely used although it is time-consuming, cumbersome and difficult to apply in routine setting of clinical microbiology laboratory. A new gradient concentration paper strip method, the Liofilchem(®) MIC test strips (MTS), provides an alternative easy and fast method enabling the simultaneous diffusion of both drugs in combination. We therefore tested a polyene+azole and an azole+echinocandin combination against 18 Candida isolates with the CHEQ method based on EUCAST guidelines and the MTS method in research and routine settings. Fractional inhibitory concentration (FIC) indices were calculated after 24 and 48 h of incubation based on complete and prominent (FIC-2) growth inhibition endpoints. Reproducibility and agreement within 1 twofold dilution was assessed. The FICs of the two methods were correlated quantitatively with t-test and Pearson analysis and qualitatively with Chi-squared test. The reproducibility of the CHEQ and MTS method was 88-100% and their agreement was 80% with 62-77% of MTS FICs being higher than the corresponding CHEQ FICs. A statistically significant Pearson correlation (r = 0.86, P = 0.0003) and association (χ(2) = 17.05, df = 4, P = 0.002) was found between MTS FIC and CHEQ FIC-2 after 24 h. Categorical agreement was 63% with no very major or major errors. All MTS synergistic interactions were also synergistic with the CHEQ method.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candidiasis; Caspofungin; Chi-Square Distribution; Drug Synergism; Drug Therapy, Combination; Echinocandins; Humans; Lipopeptides; Microbial Sensitivity Tests; Reagent Kits, Diagnostic; Reproducibility of Results; Voriconazole

Candida albicans osteomyelitis is a rare disease that occurs in immunocompromised individuals, sometimes with a late diagnosis related to the mismatch between symptoms and candidemia. This case refers to a 36-year-old male patient with a history of oesophageal surgery for achalasia with multiple subsequent surgeries and hospitalisation in the intensive care unit for oesophageal fistula complication. Four months after discharge, the patient was admitted to the infectious diseases department with pain in the 10th-12th left ribs, swelling of the 4th-6th costal cartilage and decreased visual acuity. An MRI study showed thickening and diffuse enhancement, with no defined borders in the cartilage and ribs, compatible with infection. After performing a CT-guided bone biopsy, isolated C. albicans sensitive to antifungal agents was detected. The patient started therapy with liposomal amphotericin B and maintenance fluconazole for 6 months and showed clinical and radiological improvement within this time.

Topics: Adult; Amphotericin B; Antifungal Agents; Blindness; Candida albicans; Candidiasis; Chest Pain; Fluconazole; Humans; Male; Osteomyelitis; Ribs

Fatal fungal infections in central nervous system (CNS) can occur through hematogenous spread or direct extension. At present, hydrophobic amphotericin B (AMB) is the most effective antifungal drug in clinical trials. However, AMB is hydrophobic and therefore penetrates poorly into the CNS, and therapeutic levels of AMB are hard to achieve. The transferrin receptor (TfR/CD71) located at the blood-brain barrier mediates transferrin transcytosis. In order to enhance the receptor-mediated delivery of AMB into CNS with therapeutic level, an anti-TfR antibody (OX26)-modified AMB-loaded PLA (poly[lactic acid])-PEG (polyethylene glycol)-based micellar drug delivery system was constructed. The prepared OX26-modified AMB-loaded nanoparticles (OX26-AMB-NPs) showed significant reduction of CNS fungal burden and an increase of mouse survival time. In conclusion, OX26-AMB-NPs represent a promising novel drug delivery system for intracerebral fungal infection.

Topics: Amphotericin B; Animals; Antibodies, Monoclonal; Antifungal Agents; Candida glabrata; Candidiasis; Drug Delivery Systems; Drug-Related Side Effects and Adverse Reactions; Erythrocytes; Meningitis; Mice; Mice, Inbred BALB C; Micelles; Nanoparticles; Polyethylene Glycols; Rabbits; Receptors, Transferrin; Transferrin

To identify the epidemiology of candida isolations in HRH Princess Maha Chakri Sirindhorn Medical Center and the sensitivity of all candida species to fluconazole.. Two hundred of Candida albicans and other Candida species from clinical specimens were collected from microbiological department between January 2010 and April 2012. All Candida were identified by standard methods and the sensitivity of fluconazole was tested by using fluconazole E test test.. There were 8 species of Candida in this study including: C. albicans (n = 94), C. tropicalis (n = 66), C. glabrata (n = 11), C. guilliermondii (n = 10), C. parapsilosis (n = 9), C. zeylanoides (n = 4), C. keyfr (C. pseudotropicalis) (n = 2), C. lusitaniae (n = 1), Candida species (n = 3). The percentage of non-albicans Candida spp. was slightly higher than C. albicans (53% vs. 47%). C. tropicalis was identified as the highest percentage of all non-albicans Candida spp. Fluconazole resistant strains were detected among C. albicans (35.71%), C. tropicalis (13.85%), C. guilliermondii (20.0%), and C. zeylanoides (50.0%). The common spp. with highest percentage of resistant strain was C. albicans.. Fluconazole could be used as thefirst-line antifungal for candidiasis at HRH Princess Maha Chakri Sirindhorn Medical Center. Empirical treatment with amphotericin B and steppingdown tofluconazole when sensitivity suggested might be the recommendation for severe cases in our setting.

Topics: Academic Medical Centers; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candidiasis; Fluconazole; Humans; Microbial Sensitivity Tests; Prospective Studies; United States

Colonisation may be the first step for the development of Candida infection. The source of neonatal colonisation is thought to be the hospital environment or the maternal vaginal tract. This study investigated to what extend Candida isolates in neonates are similar to isolates from their mother's vaginal tract. Vaginal samples were collected from 347 pregnant women within 48 h before delivery. Samples from oral and rectal mucosa of their neonates were collected within 24-72 h after delivery, were cultured and yeast species were identified. Antifungal susceptibility tests against six antifungal agents were performed. All paired isolates from mother and infant were genotyped by pulse field gel electrophoresis. A total of 82 mothers and of 16 infants were found colonised by Candida spp. C. albicans was the most common species in pregnant women (n = 68) followed by C. glabrata (n = 11). Only C. albicans was isolated from infants, mainly (14/16) from rectal site. All colonised neonates were born to mothers colonised by C. albicans. Candida genotyping revealed identical strains in all investigated neonate-mother pairs. All isolates were susceptible to amphotericin B. Our findings strongly suggest that vertical transmission has the principal role in the neonatal colonisation by C. albicans in the very first days of life.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Female; Genotype; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infectious Disease Transmission, Vertical; Male; Pregnancy; Pregnancy Complications, Infectious; Vagina; Young Adult

This study was aimed at finding predictors of invasive fungal infection (IFI) after pediatric allogeneic hematopoietic SCT (HSCT). All children who received allogeneic HSCT in the Wilhelmina Children's Hospital Utrecht between 2004 and 2012 were included. HSCT data were prospectively collected. Patients were retrospectively classified into high- or low-risk groups for developing IFI using criteria based on available literature. Predictors for the occurrence of IFI were analyzed using Cox regression models. We used logistic regression models to analyze the association between other HSCT-related complications and IFI. Secondary outcomes were overall survival and treatment-related mortality (TRM). Two-hundred nine patients were included in the analysis; median age was 6.6 years. The cumulative incidence of IFI was 12%. In patients classified as 'low risk' (n=75), only 5.3% developed IFI (odds ratio (OR): 0.325; P=0.047). In multivariate analysis, a predictor for the occurrence of IFI was an a priori determined HSCT TRM risk >20% (based on EBMT-risk score). Post-HSCT, the administration of high-dose steroids was associated with IFI (OR: 4.458; P=0.010). Patients who developed IFI showed an increased risk of TRM (OR: 3.773; P=0.004). These results confirm that risk group stratification should guide intensity of monitoring for IFI and use of antifungal prophylaxis.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Caspofungin; Child; Child, Preschool; Echinocandins; Female; Fusariosis; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Infant; Lipopeptides; Logistic Models; Male; Mycoses; Neutrophils; Prospective Studies; Pyrimidines; Retrospective Studies; Risk; Treatment Outcome; Triazoles; Voriconazole; Young Adult

The in vitro activities of fluconazole (FLC), amphotericin B (AmB) and caspofungin (CSP) were evaluated against three isolates of Candida lusitaniae using time-kill curves. AmB showed in vitro fungicidal activity, whilst FLC and CSP exerted mainly strain-dependent fungistatic activity. The in vivo efficacies of the three drugs were evaluated in a murine model of disseminated infection. The doses administered were FLC 50 mg/kg/day, AmB 0.8 mg/kg/day and CSP 5 mg/kg/day. All three drugs were able to reduce the fungal burden in the kidneys of infected mice, with AmB showing the highest efficacy, followed by CSP. At least in this model, FLC, AmB and CSP are good candidates for treating invasive infections by C. lusitaniae.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candidiasis; Caspofungin; Colony Count, Microbial; Disease Models, Animal; Echinocandins; Fluconazole; Kidney; Lipopeptides; Male; Mice; Microbial Sensitivity Tests; Treatment Outcome

Bloodstream infection (BSI) after allogeneic hematopoietic stem cell transplantation (HSCT) is a well-known complication during the pre-engraftment phase. Knowledge of trends in etiology and antibiotic susceptibility of BSI is important as the time to effective antibiotic treatment is closely associated with survival in bacteremic patients with septic shock.. BSI during the pre-engraftment phase was studied retrospectively in 521 patients undergoing HSCT at our center in 2001-2008. Incidence, risk factors, outcome, and microbiology findings were investigated and compared with BSI in a cohort transplanted during 1975-1996.. The incidence of at least 1 episode of BSI was 21%, the total attributable mortality of BSI was 3.3%, and crude mortality at day 120 after transplantation was 21%. The rate of gram-positive and gram-negative BSI was 80% and 13%, respectively. Gram-negative BSI was more frequent both in 2001-2004 and in 2005-2008 compared with 1986-1996 (P = 0.023 for 2001-2004, P = 0.001 for 2005-2008), with fluoroquinolone-resistant Escherichia coli as the predominant finding. BSI with viridans streptococci and E. coli occurred significantly earlier after HSCT than BSI with Enterococcus species, with median time of 4, 8, and 11 days, respectively (P < 0.01 both for viridians streptococci vs. Enterococcus species, and E. coli vs. Enterococcus species). Risk factors for BSI in multivariate analysis were transplantation from unrelated donor and cord blood as stem cell source, whereas peripheral blood as stem cell source was protective.. Despite low attributable mortality of BSI, crude mortality at day 120 after transplantation was 21%, indicating an association between BSI and other risk factors for death. The risk of gram-negative BSI increased over time in parallel with an increased rate of quinolone resistance. However, the incidence and attributable mortality of gram-negative BSI remained low. Thus, prophylaxis with ciprofloxacin is still deemed appropriate, but continued assessments of the risk and benefits of fluoroquinolone prophylaxis must be performed.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anti-Infective Agents; Bacteremia; Candidiasis; Child; Child, Preschool; Ciprofloxacin; Cohort Studies; Enterococcus; Female; Fluconazole; Fungemia; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Infant; Male; Middle Aged; Multivariate Analysis; Neutropenia; Retrospective Studies; Risk Factors; Staphylococcal Infections; Streptococcal Infections; Time Factors; Transplantation, Homologous; Viridans Streptococci; Young Adult

The oral administration of amphotericin B (AmB) has a major drawback of poor bioavailability. The aim of this study was to investigate the potential of glyceryl monoolein (GMO) cubosomes as lipid nanocarriers to improve the oral efficacy of AmB. Antifungal efficacy was determined in vivo in rats after oral administration, to investigate its therapeutic use. The human colon adenocarcinoma cell line (Caco-2) was used in vitro to evaluate transport across a model of the intestinal barrier. In vivo antifungal results showed that AmB, loaded in GMO cubosomes, could significantly enhance oral efficacy, compared against Fungizone, and that during a 2 day course of dosage 10 mg/kg the drug reached effective therapeutic concentrations in renal tissue for treating fungal infections. In the Caco-2 transport studies, GMO cubosomes resulted in a significantly larger amount of AmB being transported into Caco-2 cells, via both clathrin- and caveolae-mediated endocytosis, but not macropinocytosis. These results suggest that GMO cubosomes, as lipid nanovectors, could facilitate the oral delivery of AmB.

Topics: Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Caco-2 Cells; Candidiasis; Feasibility Studies; Humans; Male; Nanocapsules; Particle Size; Rats; Rats, Sprague-Dawley; Treatment Outcome

Tyrocidines are cationic cyclodecapeptides from Bacillus aneurinolyticus that are characterized by potent antibacterial and antimalarial activities. In this study, we show that various tyrocidines have significant activity against planktonic Candida albicans in the low-micromolar range. These tyrocidines also prevented C. albicans biofilm formation in vitro. Studies with the membrane-impermeable dye propidium iodide showed that the tyrocidines disrupt the membrane integrity of mature C. albicans biofilm cells. This membrane activity correlated with the permeabilization and rapid lysis of model fungal membranes containing phosphatidylcholine and ergosterol (70:30 ratio) induced by the tyrocidines. The tyrocidines exhibited pronounced synergistic biofilm-eradicating activity in combination with two key antifungal drugs, amphotericin B and caspofungin. Using a Caenorhabditis elegans infection model, we found that tyrocidine A potentiated the activity of caspofungin. Therefore, tyrocidines are promising candidates for further research as antifungal drugs and as agents for combinatorial treatment.

Topics: Amphotericin B; Animals; Antifungal Agents; Bacillus; Biofilms; Caenorhabditis elegans; Candida albicans; Candidiasis; Caspofungin; Cell Membrane Permeability; Drug Synergism; Echinocandins; Lipopeptides; Microbial Sensitivity Tests; Peptides; Reactive Oxygen Species; Tyrocidine

The aim of this study was to visualize the morphology of Candida albicans ATCC10231 in the absence and in the presence of amphotericin B at 0.4 μg/mL, to better understand the phenomenon responsible for a large portion of cases of treatment failure called "dormancy phenomenon". The main objective was to determine the morphological changes adopted by C. albicans in the lag phase extended before resuming normal growth.. In order to define the morphological characteristics and surface properties of the cells in the absence and in the presence of amphotericin B at 0.4 μg/mL, cells were cultured in Sabouraud medium at 30°C, and the morphology index was determined by reference to the classification of forms in C. albicans determined by Merson-Davies and Odds. Then, the technique of scanning electron microscopy (SEM) coupled with image analysis was used to measure the surface and determined the morphological properties using the plugin analysis three-dimensional (3D) integrated into the ImageJ software.. The dormant phase in C. albicans ATCC10231 grown in Sabouraud liquid at 30°C in the presence of amphotericin B at 0.4 μg/mL extends to 21 hours. The index morphology obtained for the two samples (in the absence and presence of amphotericin B) indicates that the cell even in the presence of amphotericin B retains its yeast form (Mi<1.5) The analysis of microphotography obtained by scanning electron microscopy (SEM) has shown that the cell in the presence of amphotericin B is partially deformed; the deformation is estimated at 33.25%, with various changes in the cell surface.. This study showed that the morphology of C. albicans ATCC10231 in the presence of amphotericin B at 0.4 μg/mL changes with partial deformation of the cell. This rate is insufficient to induce cell death, which partly explains the phenomenon of dormancy adopted by C. albicans prior to cell repair and resume normal growth.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Cell Shape; Drug Resistance, Fungal; Humans; Microbial Sensitivity Tests; Microscopy, Electron, Scanning

Amphotericin B (AMB) arabinogalactan (AG) conjugate was synthesized by the conjugation of AMB to oxidized AG by reductive amination. The conjugate was evaluated for in vitro antifungal activity and in vivo toxicity. Optimization of the conjugation process was investigated using large batches of 100 g, which are 20 times larger than previously reported for AMB-AG conjugation. The efficacy of AMB-AG conjugates was studied as a function of reaction conditions and time, aldehyde/reducing agent mole ratio, and purification procedure. The most potent AMB-AG conjugate having low minimal inhibitory concentration (MIC) and high maximal tolerated dose (MTD) was obtained following reduction with NaBH4 at 1:2 mol ratio (AG units/NaBH4) at 25 °C for 24 h. AMB-AG conjugate prepared under these conditions demonstrated MIC of 0.5 mg/L (equiv of AMB) in Candida albicans, and an MTD of 60 mg/kg (equiv of AMB) in mice, while AMB clinical formulation (Fungizone) demonstrated high toxicity (MTD = 3 mg/kg). These findings confirm the simplicity and reproducibility of the conjugation allowing this method to be applied on larger scale production.

Topics: Amphotericin B; Animals; Candida albicans; Candidiasis; Chlorocebus aethiops; Galactans; Male; Mice; Mice, Inbred ICR; Rats; Rats, Inbred Lew; Sheep; Vero Cells

Optisol-GS, the most common corneal storage medium in the United States, contains antibacterial but no antifungal supplementation. Most postkeratoplasty endophthalmitis and keratitis cases are now of a fungal origin.. To assess the efficacy and safety of voriconazole and amphotericin B in reducing Candida species contamination of Optisol-GS under normal storage conditions.. In vitro laboratory study using 15 pairs of research-grade donor corneas and 20-mL vials of Optisol-GS.. Twenty vials of Optisol-GS were supplemented with either voriconazole at 1×, 10×, 25×, or 50× minimum inhibitory concentration (MIC) or amphotericin B at 0.25×, 0.5×, 1×, or 10× MIC. Known concentrations of Candida albicans and Candida glabrata were each added to a set of vials. Safety studies were performed by separating 15 pairs of donor corneas into unsupplemented Optisol-GS or Optisol-GS plus an antifungal.. Efficacy outcomes were viable fungal colony counts determined from samples taken on days 2, 7, and 14 immediately after removal from refrigeration and after warming to room temperature for 2 hours. Safety outcomes included percentage of intact epithelium and endothelial cell density on days 0, 7, and 14, as well as percentage of nonviable endothelial cells by vital dye staining on day 14.. Growth of C albicans and C glabrata was observed in all voriconazole-supplemented vials. In contrast, there was no growth of either organism in amphotericin B-supplemented vials, except at 0.25× and 0.5× MIC on day 2, when viable counts of C glabrata were reduced by 99% and 96%, respectively. Compared with paired controls, with the exception of Optisol-GS plus amphotericin B at 10× MIC, donor corneas in supplemented Optisol-GS appeared to have no difference in endothelial cell density reduction, percentage of intact epithelium, or percentage of nonviable endothelial cells.. The addition of amphotericin B to Optisol-GS may significantly improve activity against contamination with Candida species, the primary cause of fungal infection after corneal transplantation. This study found significant endothelial toxic effects at the maximal concentration of amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candida glabrata; Candidiasis; Cell Count; Chondroitin Sulfates; Colony Count, Microbial; Complex Mixtures; Cornea; Culture Media, Serum-Free; Dextrans; Drug Combinations; Drug Contamination; Endothelium, Corneal; Gentamicins; Humans; Microbial Sensitivity Tests; Organ Preservation; Organ Preservation Solutions; Pyrimidines; Tissue Donors; Treatment Outcome; Triazoles; Voriconazole

Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI).. To determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City.. Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010.. All patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis.. CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days). C. albicans was the predominant species (46%), followed by C. tropicalis (26%). C. glabrata was isolated from patients with diabetes (50%), and elderly patients. Sixty-four patients (86%) received antifungals. Amphotericin-B deoxycholate (AmBD) was the most commonly used agent (66%). Overall mortality rate reached 46%, and risk factors for death were APACHE II score ≥ 16 (OR = 6.94, CI95% = 2.34-20.58, p<0.0001), and liver disease (OR = 186.11, CI95% = 7.61-4550.20, p = 0.001). Full susceptibility to fluconazole, AmBD and echinocandins among C. albicans, C. tropicalis, and C. parapsilosis was observed.. The cumulative incidence rate in these centers was higher than other reports from tertiary care hospitals from Latin America. Knowledge of local epidemiologic patterns permits the design of more specific strategies for prevention and preemptive therapy of CBSI.

Topics: Adult; Aged; Amphotericin B; Candida; Candida albicans; Candida glabrata; Candida tropicalis; Candidiasis; Deoxycholic Acid; Drug Combinations; Female; Fluconazole; Humans; Incidence; Male; Mexico; Middle Aged; Proportional Hazards Models; Prospective Studies; Regression Analysis; Risk Factors; Tertiary Care Centers; Treatment Outcome

Accurate knowledge of fungemia epidemiology requires identification of strains to the molecular level. Various studies have shown that the rate of resistance to fluconazole ranges from 2.5% to 9% in Candida spp. isolated from blood samples. However, trends in antifungal resistance have received little attention and have been studied only using CLSI M27-A3 methodology. We assessed the fungemia epidemiology in a large tertiary care institution in Madrid, Spain, by identifying isolates to the molecular level and performing antifungal susceptibility testing according to the updated breakpoints of European Committee for Antimicrobial Susceptibility Testing (EUCAST) definitive document (EDef) 7.2. We studied 613 isolates causing 598 episodes of fungemia in 544 patients admitted to our hospital (January 2007 to December 2013). Strains were identified after amplification and sequencing of the ITS1-5.8S-ITS2 region and further tested for in vitro susceptibility to amphotericin B, fluconazole, posaconazole, voriconazole, micafungin, and anidulafungin. Resistance was defined using EUCAST species-specific breakpoints, and epidemiological cutoff values (ECOFFs) were applied as tentative breakpoints. Most episodes were caused by Candida albicans (46%), Candida parapsilosis (28.7%), Candida glabrata (9.8%), and Candida tropicalis (8%). Molecular identification enabled us to better detect cryptic species of Candida guilliermondii and C. parapsilosis complexes and episodes of polyfungal fungemia. The overall percentage of fluconazole-resistant isolates was 5%, although it was higher in C. glabrata (8.6%) and non-Candida yeast isolates (47.4%). The rate of resistance to echinocandins was 4.4% and was mainly due to the presence of intrinsically resistant non-Candida species. Resistance mainly affected non-Candida yeasts. The rate of resistance to fluconazole and echinocandins did not change considerably during the study period.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candidiasis; DNA, Fungal; DNA, Intergenic; Drug Resistance, Fungal; Echinocandins; Fungemia; Humans; Microbial Sensitivity Tests; Mycological Typing Techniques; Spain; Tertiary Healthcare

The aim of this study was to evaluate possibilities of correct identification and susceptibility testing of C. glabrata clinical isolates with Integral System Yeast Plus (ISYP). For species identification, as the reference method, API Candida test and species-specific PCR reactions were used. The potential of antifungal susceptibility testing by the ISYP test was compared with the Sensititre Yeast One. Whilst the reference methods confirmed that the received population (n = 65 isolates) represented only C. glabrata, identification with the ISYP system showed correct data only in the case of 18 strains tested (27.7%). Species identification of the other 47 strains with the ISYP test was not possible at all. Significant differences were also observed for drug susceptibility testing carried out by the ISYP and the Sensititre Yeast One. The highest level of disagreement in classifying strains as resistant or susceptible estimated, as 73.9% and 40.0%, was observed for itraconazole and amphotericin B, respectively. Satisfactory results were only obtained for 5-fluorocytosine with 93.8% agreement between both methods. In our opinion the idea of the ISYP system is certainly good. The combination of identification ability and drug susceptibility testing in one test is very important, especially from a clinical point of view. However, the current version of the ISYP has many disadvantages. We would like to encourage the manufacturer to make an effort and develop a new, more accurate version of the test.

Topics: Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Fluconazole; Flucytosine; Humans; Itraconazole; Microbial Sensitivity Tests; Mycological Typing Techniques; Polymerase Chain Reaction; Sensitivity and Specificity

In kidney transplant recipients, acute renal failure resulting from a ureteral obstruction by fungus balls is uncommon. We report a 60-year-old man diagnosed with ureteral obstruction caused by Candida albicans fungus balls early after transplant. Diagnosis was made by a T2-weighted magnetic resonance image, which demonstrated fungus balls as a low-intensity mass in the pelvis and microscopic examination findings in the urine. The patient was treated successfully with an antifungal agent and direct irrigation. It should be noted that fungus balls may cause ureteral obstruction of transplanted kidneys, possibly resulting in graft failure. Imaging of the kidneys and collecting system and aggressive debridement that adds to systemic therapy are necessary for early diagnosis and are central to a successful outcome.

Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Bezoars; Candida albicans; Candidiasis; Fluconazole; Humans; Kidney Transplantation; Magnetic Resonance Imaging; Male; Middle Aged; Predictive Value of Tests; Therapeutic Irrigation; Treatment Outcome; Ureteral Obstruction

The aim of this study was to report the successful medical management of 2 cases of late-onset endothelial keratoplasty-related stromal interface infections.. All cases of endothelial keratoplasty-related infections treated with intrastromal antifungal injections were compiled. The following information was collected: demographic data, surgical indications, donor rim cultures, donor mate outcomes, clinical course, diagnostic tests, and clinical outcome.. Two cases of interface fungal keratitis diagnosed on clinical appearance and confocal microscopy were identified. Both patients refused to undergo further surgery and failed systemic and/or topical therapy. Each received 3 to 4 intrastromal injections, with secondary infusion into the graft-host interface, which resulted in the complete involution of their interface opacities.. Intrastromal antifungal injection may be an effective alternative to surgical intervention in late-onset fungal Descemet stripping endothelial keratoplasty interface keratitis. Early treatment may preserve graft viability and result in a good visual outcome without the need for either penetrating keratoplasty or potential pathogen exposure to the anterior chamber.

Topics: Administration, Oral; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Corneal Stroma; Corneal Ulcer; Descemet Stripping Endothelial Keratoplasty; Eye Infections, Fungal; Fluconazole; Humans; Infusions, Intralesional; Injections, Intraocular; Male; Microscopy, Confocal; Voriconazole

Amphotericin B (AMB) is an antifungal drug that binds to ergosterol and forms pores at the cell membrane, causing the loss of ions. In addition, AMB induces the accumulation of reactive oxygen species (ROS), and although these molecules have multiple deleterious effects on fungal cells, their specific role in the action mechanism of AMB remains unknown. In this work, we studied the role of ROS in the action mechanism of AMB. We determined the intracellular induction of ROS in 44 isolates of different pathogenic yeast species (Candida albicans, Candida parapsilosis, Candida glabrata, Candida tropicalis, Candida krusei, Cryptococcus neoformans, and Cryptococcus gattii). We also characterized the production of ROS in AMB-resistant isolates. We found that AMB induces the formation of ROS in all the species tested. The inhibition of the mitochondrial respiratory chain by rotenone blocked the induction of ROS by AMB and provided protection from the killing action of the antifungal. Moreover, this phenomenon was absent in strains that displayed resistance to AMB. These strains showed an alteration in the respiration rate and mitochondrial membrane potential and also had higher catalase activity than that of the AMB-susceptible strains. Consistently, AMB failed to induce protein carbonylation in the resistant strains. Our data demonstrate that the production of ROS by AMB is a universal and important action mechanism that is correlated with the fungicidal effect and might explain the low rate of resistance to the molecule. Finally, these data provide an opportunity to design new strategies to improve the efficacy of this antifungal.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Catalase; Cell Membrane; Cryptococcosis; Cryptococcus; Drug Resistance, Fungal; Electron Transport; Ergosterol; Membrane Potential, Mitochondrial; Microbial Sensitivity Tests; Oxidative Stress; Oxygen Consumption; Reactive Oxygen Species; Rotenone; Uncoupling Agents

Topics: Amphotericin B; Antifungal Agents; Blood Chemical Analysis; Candida; Candidiasis; Fluconazole; Humans; Hyperphosphatemia; Male; Middle Aged; Sepsis

In recent years the incidence of invasive fungal infections (IFIs) in post liver transplant (LT) has reduced to about 5%, however the majority of IFIs develops early in the post-transplant course. Candida species are the most frequent causative pathogens followed by Aspergillus species. Mortality for invasive candidiasis is still 40-50%. For this reason universal prophylaxis is still considered useful and is adopted by different LT centers, although it is not justified by available data. The aim of study is to evaluate Candida infection incidence and mortality in low risk patients and therefore not subjected to antifungal prophylaxis in the immediate post-LT.. The patient is defined low risk if without any risk factor for IFIs as reported in literature and according to our center protocol described below. We analyzed retrospectively the records (with 90 days follow-up) of all adult patients underwent to LT at our center in 2011-2012.. At our center between 2011 and 2012, 247 LT in 232 adult patients were performed: 137 patients (59%) received prophylaxis with Amphotericin B lipid complex or liposomal Amphotericin B, 95 patients (41%) didn't receive any prophylaxis. In these latter patients was observed only one case of Candida oesophagitis at the second month post-LT. The incidence of invasive candidiasis was 0%, and there wasn't mortality ascribed to Candida infection.. It is possible to identify low risk patients for IFIs post-LT and the no prophylaxis policy in the early LT course appears safe and feasible.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Female; Follow-Up Studies; Humans; Incidence; Liver Transplantation; Male; Middle Aged; Postoperative Care; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome; Watchful Waiting

Candida spp. are frequently cultured from the respiratory tract in critically ill patients. Most intensivists start amphotericin-B deoxycholate (ABDC) inhalation therapy to eradicate Candida spp. from the respiratory tract. However, the safety and efficacy of this treatment are not well established. The purpose of this study was to assess the safety and efficacy of ABDC inhalation for the treatment of respiratory Candida spp. colonization in critically ill patients.. All non-neutropenic patients admitted into the intensive care unit (ICU) of a university hospital from December 2010-2011, who had positive Candida spp. cultures of the respiratory tract for more than 1 day and required mechanical ventilation >48 h were retrospectively included. The decision to start ABDC inhalation had been made by attending intensivists on clinical grounds in the context of selective decontamination of the digestive tract. Infection characteristics and patient courses were assessed.. Hundred and thirteen consecutive patients were studied. Fifty-one of them received ABDC inhalation and their characteristics at baseline and day 1 of respiratory colonization did not differ from those of colonized patients not receiving treatment (n = 62). The ABDC-treated group had a similar Candida spp. load but did not decolonize more rapidly as compared to untreated patients. The clinical pulmonary infection and lung injury scores did not decrease as in the untreated group. In a Cox proportional hazard model, the duration of mechanical ventilation was increased (P < 0.003) by ABDC treatment independently of other potential determinants and Candida spp. colonization. No differences in ventilator-associated pneumonia or in overall mortality (up to day 90) were observed.. Treatment of respiratory Candida spp. colonization in non-neutropenic critically ill patients by inhaled ABDC may not affect respiratory colonization but may increase duration of mechanical ventilation, because of direct toxicity of the drug on the lung.

Topics: Administration, Inhalation; Adult; Aged; Amphotericin B; Candida; Candidiasis; Critical Illness; Deoxycholic Acid; Drug Combinations; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Respiration, Artificial; Respiratory Tract Infections; Retrospective Studies

A challenging case of a nonunion of the proximal femur complicated by infection attributed to microbial and fungal pathogens requiring a combination of novel surgical techniques to achieve eradication of infection, preservation of the native hip joint, and restoration of function.

Topics: Adult; Amoxicillin; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bone Cements; Candidiasis; Fluconazole; Fracture Fixation, Intramedullary; Fracture Healing; Fractures, Ununited; Hip Fractures; Humans; Male; Recovery of Function; Staphylococcal Infections; Treatment Outcome; Vancomycin; Wound Infection

Amphotericin B (AMB) is a polyene antibiotic with broad spectrum antifungal activity, but its clinical toxicities and poor solubility limit the wide application of AMB in clinical practice. Recently, new drug-loaded nanoparticles (NPs) - diblock copolymer D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (PLGA-TPGS) - have received special attention for their reduced toxicity, and increased effectiveness of drug has also been reported. This study aimed to develop AMB-loaded PLGA-TPGS nanoparticles (AMB-NPs) and evaluate their antifungal effects in vitro and in vivo.. AMB-NPs were prepared with a modified nanoprecipitation method and then characterized in terms of physical characteristics, in vitro drug release, stability, drug-encapsulation efficiency, and toxicity. Finally, the antifungal activity of AMB-NPs was investigated in vitro and in vivo.. AMB-NPs were stable and spherical, with an average size of around 110 nm; the entrapment efficacy was closed to 85%, and their release exhibited a typically biphasic pattern. The actual minimum inhibitory concentration of AMB-NPs against Candida albicans was significantly lower than that of free AMB, and AMB-NPs were less toxic on blood cells. In vivo experiments indicated that AMB-NPs achieved significantly better and prolonged antifungal effects when compared with free AMB.. The AMB-PLGA-TPGS NP system significantly improves the AMB bioavailability by improving its antifungal activities and reducing its toxicity, and thus, these NPs may become a good drug carrier for antifungal treatment.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Colony Count, Microbial; Drug Carriers; Ethylene Glycols; Kidney; Liver; Mice; Nanoparticles; Polyesters; Polyethylene Glycols; Vitamin E

Many scientists have reported Candida species to be of great concern because of the high frequency that they colonize and infect human hosts, particularly cancer patients. Moreover, in the last decades Candida species have developed resistance to many antifungal agents. Based on this, we aimed to identify and determine the prevalence of Candida spp from blood culture bottles among cancer patients and their antifungal resistance pattern.. From the blood culture bottles isolation and identification of the Candida spp were performed by conventional microbiological techniques. The in vitro antibiotic resistance pattern of the isolates was determined by CLSI guidelines. Genomic DNA was isolated and amplified. Each gene was separated by agar gel electrophoresis.. Identification of Candida spp was based on the presence of yeast cells in direct examination, culture and DNA extraction. Of the 68 blood samples collected during the study period (April 2013 to October 2013), five (7.35%) were positive for the presence of Candida spp, 2 (40%) of which were identified as Candida albicans and 3 (60%) were Candida non-albicans.. High resistance to amphotricin B was observed among all the Candida non-albicans isolates. Regular investigations into antifungal resistance will help us to get an updated knowledge about their antibiotic resistance pattern which may help the physician in selecting the antibiotics for empirical therapy.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; DNA, Fungal; Drug Resistance, Bacterial; Humans; Incidence; Neoplasms; Polymerase Chain Reaction; Prognosis

To determine the proportion of albicans and non-albicans candiduria in a hospital setting and to ascertain if fluconazole is still suitable as empirical antifungal therapy based on antifungal susceptibility patterns of Candida species.. The cross-sectional study was conducted between December 2010 and December 2011 at UKM Medical Centre, Kuala Lumpur, Malaysia and comprised 64 urine samples from patients who were either suspected or confirmed to have urinary tract infections. Yeasts were speciated using ID 32 C and subjected to antifungal susceptibility testing using Sensititre® YeastOne YO8.. Candida albicans accounted for 38(59.4%) of the isolates, Candida tropicalis 18(28.1%), Candida glabrata 6(9.4%) and Candida parapsilosis 2(3.1%). Overall, the isolates were susceptible to both amphotericin B (MIC90 1 μg/ml) and to 5-flucytosine (MIC90 0.25 μg/ml), but susceptible-dose dependent towards fluconazole (MIC90 16 μg/ml). Individually, Candida albicans was susceptible to fluconazole (MIC90 2 μg/ml), amphotericin B (MIC90 0.5 μg/ml) and 5-flucytosine (MIC90 0.25 μg/ml). Candida tropicalis was also susceptible to fluconazole (MIC90 4 μg/ml), amphotericin B (MIC90 1 μg/ml) and 5-flucytosine (MIC90 0.125 μg/ml). Candida glabrata was resistant to fluconazole (MIC90 64 μg/ml), but susceptible to amphotericin B (MIC90 1 μg/ml) and 5-flucytosine (MIC90 0.125 μg/ml). Lastly, Candida parapsilosis was resistant to fluconazole (MIC90 256 μg/ml), but susceptible to amphotericin B (MIC90 0.5 μg/ml) and 5-flucytosine (MIC90 0.5 μg/ml).. The commonest yeast associated with candiduria at the study site was Candida albicans, and fluconazole can still be used for empirical therapy of candiduria.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Cross-Sectional Studies; Dose-Response Relationship, Drug; Fluconazole; Humans; Malaysia; Microbial Sensitivity Tests; Urinary Tract Infections

Miltefosine is an alkylphosphocholine that shows broad-spectrum in vitro antifungal activities and limited in vivo efficacy in mouse models of cryptococcosis. To further explore the potential of this class of compounds for the treatment of systemic mycoses, nine analogs (3a-3i) were synthesized by modifying the choline structural moiety and the alkyl chain length of miltefosine. In vitro testing of these compounds against the opportunistic fungal pathogens Candida albicans, Candida glabrata, Candida krusei, Aspergillus fumigatus, and Cryptococcus neoformans revealed that N-benzyl-N,N-dimethyl-2-{[(hexadecyloxy)hydroxyphosphinyl]oxy}ethanaminium inner salt (3a), N,N-dimethyl-N-(4-nitrobenzyl)-2-{[(hexadecyloxy)hydroxyphosphinyl]oxy}ethanaminium inner salt (3d), and N-(4-methoxybenzyl)-N,N-dimethyl-2-{[(hexadecyloxy)hydroxyphosphinyl]oxy}ethanaminium inner salt (3e) exhibited minimum inhibitory concentrations (MIC) of 2.5-5.0 μg/mL against all tested pathogens, when compared to miltefosine with MICs of 2.5-3.3 μg/mL. Compound 3a showed low in vitro cytotoxicity against three mammalian cell lines similar to miltefosine. In vivo testing of 3a and miltefosine against C. albicans in a mouse model of systemic infection did not demonstrate efficacy. The results of this study indicate that further investigation will be required to determine the potential usefulness of the alkylphosphocholines in the treatment of invasive fungal infections.

Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Candida; Candidiasis; Cell Line; Cryptococcosis; Cryptococcus neoformans; Fungi; Humans; Mice; Mycoses; Phosphorylcholine

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Coinfection; Colonic Diseases; Colonoscopy; Humans; Male; Middle Aged; Mucormycosis; Tomography, X-Ray Computed

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Creatinine; Critical Illness; Cross Infection; Deoxycholic Acid; Drug Combinations; Fluconazole; Humans; Intensive Care Units; Practice Patterns, Physicians'; Renal Insufficiency

Candida albicans and, more recently, non-C. albicans Candida spp. are considered the most frequent fungi in hospitals. This study analyzed Candida spp. isolates and compared the frequency of different species, that is, C. albicans and non-C. albicans Candida spp., and the origins of isolates, that is, from hospital environments or infections. Yeast virulence factors were evaluated based on biofilm production and metabolic activity. Hemolysin production and the antifungal susceptibility profiles of isolates were also evaluated. Candida spp. were highly prevalent in samples collected from hospital environments, which may provide a reservoir for continuous infections with these yeasts. There were no differences in the biofilm productivity levels and metabolic activities of the environmental and clinical isolates, although the metabolic activities of non-C. albicans Candida spp. biofilms were greater than those of the C. albicans biofilms (p < 0.05). Clinical samples had higher hemolysin production (p < 0.05) and lower susceptibility to fluconazole (p < 0.05). Non-C. albicans Candida spp. predominated in samples collected from hospital environments and infections (p < 0.05). These species had a lower susceptibility to fluconazole and amphotericin B, and their biofilms had higher metabolic activities than those produced by C. albicans, which may explain the increased incidence of fungal infections with these yeasts during recent years.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida; Candidiasis; Environmental Microbiology; Fluconazole; Hemolysin Proteins; Hospitals; Humans; Microbial Sensitivity Tests; Prevalence

We herein report a renal allograft recipient five years post transplant who had bilateral lung abscesses. The abscess grew Candida tropicalis on bronchoalveolar lavage. The patient was administered amphotericin B, but succumbed to massive hemoptysis. The case highlights a fungal complication in renal transplant and need for early suspicion and prompt therapy.

Topics: Amphotericin B; Antifungal Agents; Bronchoalveolar Lavage Fluid; Candida tropicalis; Candidiasis; Fatal Outcome; Hemoptysis; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Lung Abscess; Male; Middle Aged; Treatment Outcome

The incidence of opportunistic fungal infections has increased in recent decades due to the growing proportion of immunocompromised patients in our society. Candida krusei has been described as a causative agent of disseminated fungal infections in susceptible patients. Although its prevalence remains low among yeast infections (2-5%), its intrinsic resistance to fluconazole makes this yeast important from epidemiologic aspects. Non mammalian organisms are feasible models to study fungal virulence and drug efficacy. In this work we have used the lepidopteran Galleria mellonella and the nematode Caenorhabditis elegans as models to assess antifungal efficacy during infection by C. krusei. This yeast killed G. mellonella at 25, 30 and 37°C and reduced haemocytic density. Infected larvae melanized in a dose-dependent manner. Fluconazole did not protect against C. krusei infection, in contrast to amphotericin B, voriconazole or caspofungin. However, the doses of these antifungals required to obtain larvae protection were always higher during C. krusei infection than during C. albicans infection. Similar results were found in the model host C. elegans. Our work demonstrates that non mammalian models are useful tools to investigate in vivo antifungal efficacy and virulence of C. krusei.

Topics: Amphotericin B; Animals; Antifungal Agents; Caenorhabditis elegans; Candida; Candidiasis; Fluconazole; Lepidoptera; Pyrimidines; Triazoles; Voriconazole

We report a case of a male patient with drug abuse in his medical history who was hospitalized because of a community acquired pneumonia. Subsequently the patient developed an acute lung injury (ARDS) and a fulminant purulent pericarditis accompanied by a pericardial effusion. Caused by the pericardial tamponade cardiac function was severely restricted. Due to fast diagnosis and immediate adequate therapy such as systemic anti-fungal treatment, pericardiocentesis, percutaneous drainage, and later surgical intervention the patient was treated successfully. This article describes etiology, pathophysiology and symptoms of purulent Candida-pericarditis and gives a review of existing literature regarding this extremely rare disease. In addition therapeutic options are discussed.

Topics: Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Community-Acquired Infections; Critical Care; Drainage; Echinocandins; Emergency Medical Services; Humans; Lipopeptides; Male; Middle Aged; Pericardiocentesis; Pericarditis; Prognosis; Respiratory Distress Syndrome; Substance-Related Disorders; Treatment Outcome

Antifungal resistance of Candida species is a clinical problem in the management of diseases caused by these pathogens. In this study we identified from a collection of 423 clinical samples taken from Tunisian hospitals two clinical Candida species (Candida albicans JEY355 and Candida tropicalis JEY162) with decreased susceptibility to azoles and polyenes. For JEY355, the fluconazole (FLC) MIC was 8 μg/ml. Azole resistance in C. albicans JEY355 was mainly caused by overexpression of a multidrug efflux pump of the major facilitator superfamily, Mdr1. The regulator of Mdr1, MRR1, contained a yet-unknown gain-of-function mutation (V877F) causing MDR1 overexpression. The C. tropicalis JEY162 isolate demonstrated cross-resistance between FLC (MIC > 128 μg/ml), voriconazole (MIC > 16 μg/ml), and amphotericin B (MIC > 32 μg/ml). Sterol analysis using gas chromatography-mass spectrometry revealed that ergosterol was undetectable in JEY162 and that it accumulated 14α-methyl fecosterol, thus indicating a perturbation in the function of at least two main ergosterol biosynthesis proteins (Erg11 and Erg3). Sequence analyses of C. tropicalis ERG11 (CtERG11) and CtERG3 from JEY162 revealed a deletion of 132 nucleotides and a single amino acid substitution (S258F), respectively. These two alleles were demonstrated to be nonfunctional and thus are consistent with previous studies showing that ERG11 mutants can only survive in combination with other ERG3 mutations. CtERG3 and CtERG11 wild-type alleles were replaced by the defective genes in a wild-type C. tropicalis strain, resulting in a drug resistance phenotype identical to that of JEY162. This genetic evidence demonstrated that CtERG3 and CtERG11 mutations participated in drug resistance. During reconstitution of the drug resistance in C. tropicalis, a strain was obtained harboring only defective Cterg11 allele and containing as a major sterol the toxic metabolite 14α-methyl-ergosta-8,24(28)-dien-3α,6β-diol, suggesting that ERG3 was still functional. This strain therefore challenged the current belief that ERG11 mutations cannot be viable unless accompanied by compensatory mutations. In conclusion, this study, in addition to identifying a novel MRR1 mutation in C. albicans, constitutes the first report on a clinical C. tropicalis with defective activity of sterol 14α-demethylase and sterol Δ(5,6)-desaturase leading to azole-polyene cross-resistance.

Topics: Amino Acid Sequence; Amino Acid Substitution; Amphotericin B; Antifungal Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Azoles; Base Sequence; Candida albicans; Candida glabrata; Candida tropicalis; Candidiasis; Cytochrome P-450 Enzyme System; Drug Resistance, Fungal; Ergosterol; Fluconazole; Fungal Proteins; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Polyenes; Pyrimidines; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sequence Analysis, DNA; Triazoles; Tunisia; Voriconazole

A comprehensive comparative analysis of the structure-antifungal activity relationships for the series of biosynthetically engineered nystatin analogues and their novel semisynthetic derivatives, as well as amphotericin B (AMB) and its semisynthetic derivatives, was performed. The data obtained revealed the significant influence of the structure of the C-7 to C-10 polyol region on the antifungal activity of these polyene antibiotics. Comparison of positions of hydroxyl groups in the antibiotics and in vitro antifungal activity data showed that the most active are the compounds in which hydroxyl groups are in positions C-8 and C-9 or positions C-7 and C-10. Antibiotics with OH groups at both C-7 and C-9 had the lowest activity. The replacement of the C-16 carboxyl with methyl group did not significantly affect the in vitro antifungal activity of antibiotics without modifications at the amino group of mycosamine. In contrast, the activity of the N-modified derivatives was modulated both by the presence of CH3 or COOH group in the position C-16 and by the structure of the modifying substituent. The most active compounds were tested in vivo to determine the maximum tolerated doses and antifungal activity on the model of candidosis sepsis in leukopenic mice (cyclophosphamide-induced). Study of our library of semisynthetic polyene antibiotics led to the discovery of compounds, namely, N-(L-lysyl)-BSG005 (compound 3n) and, especially, L-glutamate of 2-(N,N-dimethylamino)ethyl amide of S44HP (compound 2j), with high antifungal activity that were comparable in in vitro and in vivo tests to AMB and that have better toxicological properties.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Cyclophosphamide; Drug Evaluation, Preclinical; Leukopenia; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Nystatin; Polyenes; Sepsis; Small Molecule Libraries; Structure-Activity Relationship

Infection is the third commonest cause of total hip arthroplasty failure. Infections of the hip with Candida species are extremely rare with only a few reports in the literature. A case of a 76-year-old female subject is presented illustrating both the difficulty in initial diagnosis and the challenges faced in hip reconstruction.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida tropicalis; Candidiasis; Debridement; Female; Hip Prosthesis; Humans; Prosthesis-Related Infections; Reoperation

In recent decades the incidence of Candida endocarditis has increased dramatically. Despite the application of surgery and antifungal therapy, Candida endocarditis remains a life-threatening infection with significant morbidity and mortality. We report a 37-year-old male drug abuser presenting with high fever, chest pain, loss of appetite and cardiac failure. His echocardiography revealed mobile large tricuspid valve vegetations. Fungal endocarditis was confirmed by culturing of the resected vegetation showing mixed growth of Candida albicans and Candida tropicalis, although three consecutive blood cultures were negative for Candida species. Phenotypic identification was reconfirmed by sequencing of the internal transcribed spacer (ITS rDNA) region. The patient was initially treated with intravenous fluconazole (6 mg kg(-1) per day), followed by 2 weeks of intravenous amphotericin B deoxycholate (1 mg kg(-1) per day). Although MICs were low for both drugs, the patient's antifungal therapy combined with valve replacement failed, and he died due to respiratory failure.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida albicans; Candida tropicalis; Candidiasis; Coinfection; Deoxycholic Acid; DNA, Fungal; DNA, Ribosomal Spacer; Drug Combinations; Drug Users; Echocardiography; Endocarditis; Fatal Outcome; Fluconazole; Humans; Male; Molecular Sequence Data; Mycological Typing Techniques; Sequence Analysis, DNA; Substance-Related Disorders; Tricuspid Valve

Endocarditis caused by Candida dubliniensis is a rare event and limited to few case reports. In this report, the authors present a patient with a history of intravenous drug use and hepatitis C and endocarditis involving a prosthetic aortic valve. Also reviewed are the treatment guidelines for Candida sp. endocarditis.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Echinocandins; Endocarditis; Fluconazole; Humans; Lipopeptides; Male; Micafungin; Middle Aged

Candida albicans causes opportunistic systemic infections with high mortality (30%-50%). Despite significant nephrotoxicity, amphotericin (AmB) is still used for the treatment of this serious fungal infection. Therefore, alternative treatments are urgently needed. Dialyzable leukocyte extracts have been used successfully to treat patients with mucocutaneous candidiasis, but their effectiveness in systemic candidiasis has not been evaluated. In this study, low-dose AmB (0.1 mg/kg) plus 10 pg of murine dialyzable spleen extracts (mDSE) were tested in a systemic candidiasis mouse model. Survival, tissue fungal burden, kidney damage, kidney cytokines, and serum levels of IL-6 and hepcidin were evaluated. Our results showed that the combined treatment of low-dose AmB plus mDSE improved survival and reduced kidney fungal burden and histopathology; these effects correlated with increased kidney concentration of IFN- γ and TGF- β 1, decreased levels of TNF- α , IL-6, and IL-10, as well as high levels of systemic IL-6 and hepcidin. Low-dose AmB and mDSE synergized to clear the infectious agent and reduced tissue damage, confirming the efficacy of a low dose of AmB, which might decrease the risk of drug toxicity. Further studies are necessary to explore these findings and its implications in future therapeutic approaches.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Cytokines; Disease Models, Animal; Female; Hepcidins; Interleukin-6; Kidney; Lymphokines; Mice; Spleen

Colonisation of the lower respiratory tract with Candida species occurs in 25% of mechanically ventilated critically ill patients, and is associated with increased morbidity. Nebulised amphotericin B has been used to eradicate Candida as part of selective decontamination of the digestive tract (SDD) protocols, but its effectiveness is unknown. We aimed to determine the effectiveness of nebulised amphotericin B in eradicating Candida respiratory tract colonisation in patients receiving SDD.. We included consecutive mechanically ventilated patients during a four-year period. Microbiological screening was performed upon admission and twice weekly thereafter according to a standardised protocol. A colonisation episode was defined as the presence of Candida species in two consecutive sputum samples taken at least one day apart. To correct for time-varying bias and possible confounding, we used a multistate approach and performed time-varying Cox regression with adjustment for age, disease severity, Candida load at baseline and concurrent corticosteroid use.. Among 1,819 patients, colonisation with Candida occurred 401 times in 363 patients; 333 of these events were included for analysis. Decolonisation occurred in 51 of 59 episodes (86%) and in 170 of 274 episodes (62%) in patients receiving and not receiving nebulised amphotericin B, respectively. Nebulised amphotericin B was associated with an increased rate of Candida eradication (crude HR 2.0; 95% CI 1.4 to 2.7, adjusted HR 2.2; 95% CI 1.6 to 3.0). Median times to decolonisation were six and nine days, respectively. The incidence rate of ventilator-associated pneumonia, length of stay and mortality did not differ between both groups.. Nebulised amphotericin B reduces the duration of Candida colonisation in the lower respiratory tracts of mechanically ventilated critically ill patients receiving SDD, but data remain lacking that this is associated with a meaningful improvement in clinical outcomes. Until more evidence becomes available, nebulised amphotericin B should not be used routinely as part of the SDD protocol.

Topics: Administration, Inhalation; Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Critical Illness; Decontamination; Digestive System; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Netherlands; Pneumonia, Ventilator-Associated; Respiratory System

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cross Infection; Deoxycholic Acid; Humans

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cross Infection; Deoxycholic Acid; Humans

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cross Infection; Deoxycholic Acid; Humans

An oral lipid based formulation that exhibits tropical stability (iCo-010) was developed to enhance the absorption of orally administered amphotericin B (AmB). iCo-010 has previously shown high efficacy in an acute model of systemic candidiasis in rats, directing the focus of this study to be its efficacy in a chronic model of systemic candidiasis in mice.. Mice were infected with 0.6 to 1×108 CFUs of Candida albicans ATCC 18804 strain by tail vein injection and were left for three days to develop the infection after which time treatment was initiated. The infected animals were assigned to the following treatment groups: no treatment (control) or iCo-010 at 5, 10 and 20 mg/kg administered by oral gavage once daily (QD) for 5 consecutive days. The animals were sacrificed 7 days after the last dose and the concentration of AmB and the fungal burden were assessed within the liver, kidneys, heart, lungs, spleen and brain.. Although the infection was relatively low (~ 60-100 CFUs/ 1 ml tissue homogenate) in the liver, lungs and heart, the infection level was very high (70 000 CFUs / 1 ml tissue homogenate) in the kidney tissues for the control group. The highest concentrations of AmB were recovered in the kidneys and the spleen. The fungal burden in the tissues was lowered by 69-96% in the treatment groups when compared to the control group.. Oral iCo-010 is an effective treatment of systemic candidiasis in the mouse model.

Topics: Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Colony Count, Microbial; Dose-Response Relationship, Drug; Drug Compounding; Heart; Kidney; Liver; Lung; Mice; Mice, Inbred BALB C; Oleic Acids; Organ Specificity; Polyethylene Glycols; Spleen; Treatment Outcome

The evolution of drug resistance in microbial pathogens provides a paradigm for investigating evolutionary dynamics with important consequences for human health. Candida albicans, the leading fungal pathogen of humans, rapidly evolves resistance to two major antifungal classes, the triazoles and echinocandins. In contrast, resistance to the third major antifungal used in the clinic, amphotericin B (AmB), remains extremely rare despite 50 years of use as monotherapy. We sought to understand this long-standing evolutionary puzzle. We used whole genome sequencing of rare AmB-resistant clinical isolates as well as laboratory-evolved strains to identify and investigate mutations that confer AmB resistance in vitro. Resistance to AmB came at a great cost. Mutations that conferred resistance simultaneously created diverse stresses that required high levels of the molecular chaperone Hsp90 for survival, even in the absence of AmB. This requirement stemmed from severe internal stresses caused by the mutations, which drastically diminished tolerance to external stresses from the host. AmB-resistant mutants were hypersensitive to oxidative stress, febrile temperatures, and killing by neutrophils and also had defects in filamentation and tissue invasion. These strains were avirulent in a mouse infection model. Thus, the costs of evolving resistance to AmB limit the emergence of this phenotype in the clinic. Our work provides a vivid example of the ways in which conflicting selective pressures shape evolutionary trajectories and illustrates another mechanism by which the Hsp90 buffer potentiates the emergence of new phenotypes. Developing antibiotics that deliberately create such evolutionary constraints might offer a strategy for limiting the rapid emergence of drug resistance.

Topics: Amphotericin B; Animals; Biological Evolution; Candida albicans; Candidiasis; Disease Models, Animal; Drug Resistance, Fungal; Ergosterol; Fungal Proteins; Genetic Fitness; Host-Pathogen Interactions; HSP90 Heat-Shock Proteins; Humans; Mice; Microbial Sensitivity Tests; Microbial Viability; Mutation; Reproducibility of Results; Stress, Physiological; Virulence

NanoDisk-amphotericin B (ND-AMB) is a protein-phospholipid bioparticle containing a "super aggregate" form of antifungal AMB. While lipid-based formulations of AMB, including liposomal AMB (L-AMB), are safer than the deoxycholate (DOC) solubilized form (DOC-AMB), the potency of lipid-based formulations is attenuated. We have developed an AMB-based therapy that is both well tolerated and fully efficacious.. Potency was determined using broth culture growth-inhibition assays and candidacidal kinetics by quantitative culture plating. Toxicology studies were performed in healthy mice. Efficacy was assessed using both immune-competent and leukopenic murine models of systemic Candida albicans infection.. ND-AMB C. albicans and Aspergillus fumigatus minimum inhibitory concentrations were fourfold and sixfold lower, respectively, than that observed for L-AMB. ND-AMB exhibited candidacidal activity at 0.125 mg/L, 16-fold lower than L-AMB. In mice, ND-AMB produced no statistically significant kidney or liver toxicity at 15 mg/kg, the highest dose tested. When evaluated in immune-competent mice infected with C. albicans, ND-AMB was at least as effective as DOC-AMB or L-AMB. In a leukopenic model of candidiasis, the 50% effective dose of ND-AMB was around threefold lower than L-AMB.. These results indicate that ND-AMB exhibits a more favorable safety profile while maintaining uncompromised antifungal properties compared to both DOC-AMB and L-AMB. ND-AMB is a promising therapy for the treatment of invasive fungal infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Female; Kaplan-Meier Estimate; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Nanostructures; Toxicity Tests

The objective of this study was to evaluate the antifungal activity of farnesol and its interaction with traditional antifungals against drug-resistant strains of Candida species. To do so, we studied the minimum in vitro inhibitory concentration (MIC) of amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), caspofungin (CAS) and farnesol against 45 isolates of Candida spp., i.e., 24 C. albicans, 16 C. parapsilosis and 5 C. tropicalis through the use of the broth microdilution method. Then, the isolates were tested with the combination of farnesol plus drugs to which they were previously found to be resistant. Additionally, the strains were pre-incubated at sub-inhibitory farnesol concentrations and their antifungal susceptibilities were re-evaluated. We found the MIC values for farnesol varied from 4.68-150 µM for Candida spp., with 19 isolates having a MIC > 1 mg/l, 18 a MIC ≥ 64 mg/l, 35 having a MIC ≥ 1 mg/l and 6 isolates a MIC ≥ 2 mg/l or were resistant to AMB, FLC, ITC and CAS, respectively. Significant MIC reductions were observed when farnesol and antifungal drugs were combined (P < 0.05) and when Candida strains were incubated with farnesol (P < 0.05). We conclude that the in vitro effects of farnesol improved the activity of traditional antifungals to which the Candida spp. isolates were resistant. These results support further investigation of the role of farnesol in the balance of the sterol biosynthetic pathway and how it interferes with cell viability.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candidiasis; Caspofungin; Drug Resistance, Fungal; Drug Synergism; Echinocandins; Farnesol; Fluconazole; Humans; Itraconazole; Lipopeptides; Microbial Sensitivity Tests

We evaluated the postantifungal effects (PAFEs) of caspofungin (CAS), voriconazole (VOR), amphotericin B (AmB), and the combinations of CAS + VOR and CAS + AmB against 30 clinical Candida krusei isolates at 0.25, 1 and 4 times the MIC of each individually and in the indicated combinations. Antifungals were removed after 1 hour and colony counts were performed at 0, 2, 6, 24, and 48 h. VOR did not display any measurable PAFE regardless of antifungal concentrations, while AmB and CAS exhibited dose-dependent PAFE. The most effective agent producing a prolonged PAFE in this study was CAS. Although the combination of CAS with VOR generated longer PAFEs at 0.25 and 1 times their respective MICs in comparison with CAS alone, this combination was indifferent rather than synergistic. However, the combination of CAS with AmB at 4 times their MICs exhibited the best performance, reducing the colony counts during the 48 h after removal of drugs and resulted in synergic interaction in respect to 20 (67%) isolates. Consequently, CAS has a prolonged PAFE in vitro against C. krusei isolates, and the combination of AmB + CAS may increase significantly the efficacy of CAS. Our data may be useful in optimizing dosing regimens for these agents and their combinations, although further studies are needed to explore the clinical usefulness of our results.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Colony Count, Microbial; Drug Synergism; Echinocandins; Humans; Lipopeptides; Microbial Sensitivity Tests; Pyrimidines; Time Factors; Triazoles; Voriconazole

Topics: Adult; Amphotericin B; Antifungal Agents; Buprenorphine; Candidiasis; Endocarditis; Endophthalmitis; Eye Infections, Fungal; Fatal Outcome; Flucytosine; Hepatitis C, Chronic; Heroin Dependence; Humans; Male; Mycoses; Pneumonia, Staphylococcal; Recurrence; Shock, Cardiogenic; Substance Abuse, Intravenous; Tricuspid Valve; Ultrasonography

The purpose of this investigation was to assess the prevalence of upper urinary tract involvement in patients with candiduria by means of (111)indium-oxine-labeled leukocyte scintigraphy. An observational cohort study of patients with confirmed candiduria was conducted in an acute-care teaching hospital in Spain from March 2006 through February 2009. An (111)In-labeled leukocyte scan was performed in order to assess the upper urinary tract involvement. A series of non-matched patients without candiduria nor bacteriuria undergoing scintigraphy to exclude infections in other sites than the urinary tract was also studied. Demographics, baseline illness, and clinical data were recorded. Candiduria was detected in 428 patients, and scintigraphy was performed in 35 of these patients. Twenty-nine patients without candiduria nor bacteriuria were also studied. Positive renal scintigraphy was documented in 24 (68%) patients with confirmed candiduria and in 3 (10%) patients without candiduria (p < 0.005). Renal uptake was not associated with a higher mortality nor with re-admissions. Subclinical pyelonephritis could be more frequent in patients with candiduria than it has been previously considered.

Topics: Aged; Aged, 80 and over; Amphotericin B; Candida; Candidiasis; Cohort Studies; Female; Humans; Indium; Male; Middle Aged; Prevalence; Pyelonephritis; Radionuclide Imaging; Spain; Urinary Tract; Urinary Tract Infections

The purpose of this investigation was to describe the characteristics of the use of systemic antifungal agents (AFAs) and to evaluate their appropriateness of use. A prospective drug-utilisation study was conducted in intensive-care areas: haematology-oncology services and transplant units. Data were collected in three periods over 9 months. The required sample size was determined to be 113 patients (margin of error ±7%, 95% confidence interval [CI]), assuming a variability of 50%. Two different investigator groups evaluated the appropriateness of use separately; Cohen's Kappa index was used to calculate the degree of agreement between groups. A total of 114 patients we included, of which 62 (54.4%) were children. A total of 150 prescriptions were administered; fluconazole was the most frequently prescribed (38%), followed by liposomal amphotericin B (22.7%) and caspofungin (18.7%). The indications were: (1) pre-emptive treatment of Candida in non-neutropaenic critically ill patients (35.1%), (2) treatment of systemic fungal infection (24.6%), (3) prophylaxis for systemic fungal infection (SFI) in immunocompromised patients (16.7%), (4) prophylaxis of SFI in transplant recipients (12.3%), (5) prophylaxis of SFI in preterm infants (5.3%), (6) treatment of SFI in neonates (6.1%). The Kappa index showed a substantial agreement (Kappa = 0.73). The indications were considered to be inappropriate in 71 (47.3%) episodes. The indications or dosages were inappropriate in 79 cases (52.7%). The indications, dosages or duration of treatment were inappropriate in 83 cases (55.3%). We conclude that AFAs are prescribed for a significant number of inappropriate indications.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Candida; Candidiasis; Caspofungin; Child; Child, Preschool; Drug Utilization; Echinocandins; Female; Fluconazole; Humans; Immunocompromised Host; Inappropriate Prescribing; Infant; Intensive Care Units; Lipopeptides; Male; Middle Aged; Mycoses; Prospective Studies; Transplantation; Young Adult

Treatment of invasive Candida krusei infections can be difficult due to its intrinsic fluconazole resistance and its reduced susceptibility to amphotericin B and flucytosine. Caspofungin (CAS) acts on a different cellular target, and its combination with voriconazole (VOR) or amphotericin B (AmB) appears promising. We evaluated the activity of CAS, VOR and AmB alone and in combination at 1/4, 1, 4xMIC concentrations by time-kill method against 30 C. krusei isolates. All isolates were susceptible to CAS and VOR; AmB MICs were 2 μg/ml for 50% of isolates by broth microdilution. CAS showed a fast killing activity at all concentrations; it was fungistatic at 1/4xMICs and fungicidal at 1-4xMICs in general. VOR displayed a concentration-independent fungistatic activity against all isolates. AmB exhibited a concentration-dependent activity; it was fungistatic at 1/4-1xMIC and fungicidal at 4xMIC. The most common interaction was indifference for both combinations. Frequency of synergic interaction for the VOR + CAS combination was 66.7% at 1/4xMIC after 48 h. The best results for CAS + AmB combination were obtained at 4xMIC in the first 4-8 h; synergic interaction was detected for 20 isolates (66.7%) at 4xMIC after 4 h. Consequently, VOR and CAS alone have been found effective, and high AmB MICs are remarkable against clinical C. krusei isolates in vitro. The combinations of CAS with VOR or AmB have exhibited promising results.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Echinocandins; Humans; Lipopeptides; Microbial Sensitivity Tests; Microbial Viability; Pyrimidines; Time Factors; Triazoles; Voriconazole

The aim of this study was to apply the microfluidic cell-chip technology for susceptibility testing. The cell-chip technology was tested with ATCC Candida strains to determine their viability and susceptibility against amphotericin B and fluconazole. Fungal cells were labelled by Sytox Green, and measurements were carried out in the cell chips of the Agilent Bioanalyzer 2100 system. Results obtained by the chip technology were compared with the standard macrodilution method and conventional flow cytometry. Determination of minimum inhibitory concentration values was based on the differentiation between living and dead cells. The cell-chip method was found to be suitable for the detection of Candida cells, for the differentiation between dead and living cells and for the determination of amphotericin B and fluconazole susceptibility of fungal cells. The minimum inhibitory concentration values obtained by the standard macrodilution, the flow cytometry and the cell-chip method showed good correlation.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Humans; Lab-On-A-Chip Devices; Microbial Sensitivity Tests; Microfluidic Analytical Techniques

Candida infections associated with catheters remain difficult to manage. Antifungal lock strategies could be a therapeutic option when the device is difficult to remove or in combination with systemic treatment to increase efficacy. This study deals with the antibiofilm potential of liposomal amphotericin B (L-AMB) used as a lock solution to inhibit Candida albicans, Candida glabrata and Candida parapsilosis biofilms in vitro.. Biofilms aged 12 h and 5 days were formed on silicone catheters. L-AMB (200 or 1000 mg/L) was added to biofilms and catheters were incubated for 4, 12 or 24 h at 37°C. L-AMB was then removed by washing. The metabolic activity of yeasts was assessed by the XTT method up to 48 h after the end of the locks to evaluate the persistence of the antibiofilm activity. Controls without antifungal were used as references to calculate the inhibition percentages induced by L-AMB lock solutions.. L-AMB (200 and 1000 mg/L) inhibited, for up to 48 h, C. albicans and C. glabrata biofilms by >70%, regardless of the lock duration. The activity of L-AMB (200 mg/L) against C. parapsilosis mature biofilms was lower and less sustained, especially for 4 h locks.. L-AMB (1000 mg/L) lock solutions strongly inhibited Candida spp. in young and mature biofilms for up to 48 h after the end of the lock. However, overall eradication of the biofilm was not obtained using 1000 mg/L L-AMB as a single lock. These results suggest the usefulness of systemic treatment combined with an L-AMB lock to control Candida spp. biofilms associated with catheters.

Topics: Amphotericin B; Antifungal Agents; Biocompatible Materials; Biofilms; Candida; Candidiasis; Catheter-Related Infections; Catheters; Disinfection; Humans; Microbial Viability; Silicones; Staining and Labeling; Tetrazolium Salts

A 67-year-old man developed dysuria and position-dependent obstructive voiding symptoms after undergoing holmium laser ablation of the prostate (HOLAP) for benign prostatic hypertrophy. A large fungal (candidal) ball adherent to the bladder wall was removed by loop excision, but the bezoar recurred in 2 weeks despite systemic fluconazole and intravesical amphotericin B. A second attempt at endoscopic removal with ultrasonic lithotripsy, endoscopic graspers, and fulguration was also unsuccessful. The patient underwent open partial cystectomy to remove his invasive fungal bezoar. Convalescence was unremarkable. Urinalysis, culture, and follow-up cystoscopy after partial cystectomy demonstrated successful definitive treatment of the fungal ball.

Topics: Aged; Amphotericin B; Antifungal Agents; Bezoars; Candidiasis; Combined Modality Therapy; Cystectomy; Cystoscopy; Dysuria; Electrocoagulation; Fluconazole; Humans; Laser Therapy; Lasers, Solid-State; Lithotripsy; Male; Postoperative Complications; Prostatic Hyperplasia; Recurrence; Urinary Bladder; Urinary Tract Infections

Descriptive values were determined for eight antifungal agents within the course of a multi-centre study encompassing 1062 German and Austrian clinical yeast isolates. Candida albicans (54%) was the predominant species isolated followed by Candida glabrata (22%), Candida parapsilosis (6%), Candida tropicalis (5.7%), Candida krusei (4.3%), as well as eleven further candidal and four non-Candida yeast species. While 519 (48.9%) isolates were tested susceptible to all antifungals tested, no isolate was found to exhibit complete cross resistance. For C. albicans, the proportions of susceptible isolates were 93.2% (amphotericin B), 95.6% (flucytosine), 84.3% (fluconazole), 83.8% (posaconazole), 91.8% (voriconazole), 96.5% (anidulafungin), 96.2% (caspofungin) and 97.6% (micafungin). Patterns of complete parallel resistances were observed within azoles (8.8%) and echinocandins (1.7%). While a decreased susceptibility was found infrequently for echinocandins and flucytosine, it was more common for azoles with highest proportions for isolates of C. glabrata (fluconazole, 40.6%; posaconazole, 37.2%), Candida guilliermondii (fluconazole and posaconazole, each 25.0%), C. krusei (posaconazole, 28.3%; voriconazole, 60%), C. parapsilosis (fluconazole, 70.3%) and C. tropicalis (fluconazole, 62.3%). The descriptive values obtained in this study represent a valid basis for the comparison of recent and future epidemiological surveys to analyse the susceptibility of yeast isolates towards major antifungal substances.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candidiasis; Echinocandins; Female; Flucytosine; Humans; Male; Microbial Sensitivity Tests

To determine the epidemiological characteristics and outcome of Candida keratitis in a Cornea Care Unit of Kolkata-based tertiary eye hospital.. A retrospective, noncomparative, observational case series involving patients of culture-proven fungal keratitis from January 2008 to December 2008. A total of 85 cases of culture-proven fungal keratitis were identified. Of these, 16 cases were caused by Candida sp and selected for the study. The records were analyzed for demographics, risk factors, mode of management (medical or surgical), indication of surgical therapy, and the response to treatment with final outcome. Medical therapy consisted of topical amphotericin B with or without intracameral application after obtaining culture reports. Surgical therapy included application of tissue adhesive with bandage contact lens and therapeutic keratoplasty.. All cases of Candida keratitis were caused by Candida albicans accounting for 16 cases [18.81%; 95% confidence interval (CI), 11.8-28.5] of total culture-positive fungal keratitis. We found postsurgical steroid therapy in 8 cases as most important association, followed by diabetes and trauma (4 cases each) as next common comorbidities. All patients required therapeutic keratoplasty. Surgical indications were corneal melt in 10 cases (62.5%; 95% CI, 38.5-81.6), extension up to limbus in 2 cases (12.5%; 95% CI, 12.2-37.2) and nonresponse with worsening in 4 cases (25%; 95% CI, 19.7-49.9). Final outcome consists of phthisis bulbi in 3 cases (18.8%; 95% CI, 5.8-43.8), failed graft in 7 cases (43.7%; 95% CI, 23-66.8), and clear graft in 6 cases (37.5%; 95% CI, 18.4-61.5).. Candida is a new concern in developing countries like India. We are concerned about the poorer outcome, probably resulting from our unpreparedness and failure of medical therapy leading to more complication and requiring surgical intervention in higher numbers.

Topics: Administration, Topical; Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Contact Lenses; Corneal Ulcer; Debridement; Eye Infections, Fungal; Female; Humans; India; Keratoplasty, Penetrating; Male; Middle Aged; Occlusive Dressings; Retrospective Studies; Risk Factors

To determine the incidence, clinical features, and outcomes of infectious endophthalmitis after Boston Type 1 Keratoprosthesis (KPro) implantation.. Retrospective, consecutive case series. Chart review of 105 patients (126 eyes) who had KPro implantation at Cincinnati Eye Institute between November 2004 and November 2010 and who were followed up for at least 1 month (range, 1 month to 66 months; mean 25 months) revealed 3 cases who developed infectious endophthalmitis.. One patient had a history of congenital glaucoma, and 2 patients had Stevens-Johnson syndrome. Two had KPro implantation for penetrating keratoplasty failure and 1 had necrosis of a previous KPro cornea. The incidence of endophthalmitis was 2.4%. All patients wore a contact lens and were on vancomycin and a fourth-generation fluoroquinolone (moxifloxacin). Vitreous fluid cultures yielded Ochrobactrum anthropi, Candida parapsilosis, and Candida albicans. All patients received intravitreal amphotericin, vancomycin, and/or ceftazidime. Topical and oral antiinfective agents were tailored based on sensitivities. One patient required KPro removal and therapeutic penetrating keratoplasty. Vision did not recover for 2 patients who presented with vision decreased to light perception. One patient, who presented with decreased vision of 20/400, recovered to 20/60.. Infectious endophthalmitis is a devastating complication that can occur after Boston KPro implantation even with prophylactic vancomycin, a fourth-generation fluoroquinolone, and a therapeutic contact lens. Fungal and gram-negative organisms are a growing cause for concern. Further study is needed on optimal prophylaxis regimens, including the use of antifungals, especially for high-risk eyes, such as those with autoimmune cicatrizing disease.

Topics: Administration, Oral; Aged; Amphotericin B; Artificial Organs; Candida albicans; Candidiasis; Ceftazidime; Cornea; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Bacterial; Eye Infections, Fungal; Female; Graft Rejection; Gram-Negative Bacterial Infections; Humans; Incidence; Intravitreal Injections; Middle Aged; Ochrobactrum anthropi; Postoperative Complications; Prostheses and Implants; Prosthesis Implantation; Reoperation; Retrospective Studies; Vancomycin; Vitreous Body; Young Adult

Oils of Cymbopogon citratus and Syzygium aromaticum have been used in traditional medicine to treat fungal infections of skin, mouth, urinary and vaginal tract in Asian countries particularly India and other developing countries.. To evaluate essential oils of Cymbopogon citratus and Syzygium aromaticum for their anti-biofilm activity against strong biofilm forming strains of Candida albicans.. XTT reduction assay, Time kill assays, light microscopy and scanning electron microscopy (SEM) were employed to determine the effect of test oils on the Candida albicans biofilms.. Most of the Candida albicans strains tested displayed formation of moderate to strong biofilms. Preformed Candida biofilms showed ≥1024 times increased resistance to antifungal drugs, 2 times to Syzygium aromaticum, but no increased tolerance for Cymbopogon citratus. Test oils were more active against preformed biofilms compared to amphotericin B and fluconazole. At 0.5× MIC, Cymbopogon citratus followed by Syzygium aromaticum were most inhibitory against biofilm formation. Light and electron microscopic studies revealed the deformity of three dimensional structures of biofilms formed in the presence of sub-MICs of Cymbopogon citratus. The cell membranes appeared to be the target site of compounds in sessile cells as displayed by SEM observations.. Our data had demonstrated promising in vitro anti-biofilm activity by Cymbopogon citratus and Syzygium aromaticum and confirm the ethnopharmacological use of these oils in muco-cutaneous Candida infections. Furthermore, it suggests exploitation of these oils as new anti-biofilm products to deal with the problem of drug-resistance and recurrent infection associated with biofilm mode of growth of Candida spp.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Cell Membrane; Cymbopogon; Drug Resistance; Fluconazole; Microbial Sensitivity Tests; Microscopy; Oils, Volatile; Phytotherapy; Plant Extracts; Syzygium

Systemic Candidia infections are of major concern in neonates, especially in those with risk factors such as longer use of broad spectrum antibiotics. Recent studies showed that also term babies with underlying gastrointestinal or urinary tract abnormalities are much more prone to systemic Candida infection. We report a very rare case of candidiasis caused by Candida kefyr in a term neonate.. Renal agenesis on the left side was diagnosed antenatally and anal atresia postnatally. Moreover, a vesico-ureteral-reflux (VUR) grade V was detected by cystography. The first surgical procedure, creating a protective colostoma, was uneventful. Afterwards our patient developed urosepsis caused by Enterococcus faecalis and was treated with piperacillin. The child improved initially, but deteriorated again. A further urine analysis revealed Candida kefyr in a significant number. As antibiotic resistance data about this non-albicans Candida species are limited, we started liposomal amphotericin B (AMB), but later changed to fluconazole after receiving the antibiogram. Candiduria persisted and abdominal imaging showed a Candida pyelonephritis. Since high grade reflux was prevalent we instilled AMB into the child's bladder as a therapeutic approach. While undergoing surgery (creating a neo-rectum) a recto-vesical fistula could be shown and subsequently was resected. The child recovered completely under systemic fluconazole therapy over 3 months.. Candidiasis is still of major concern in neonates with accompanying risk factors. As clinicians are confronted with an increasing number of non-albicans Candida species, knowledge about these pathogens and their sensitivities is of major importance.

Topics: Amphotericin B; Antifungal Agents; Anus, Imperforate; Candida; Candidiasis; Congenital Abnormalities; Enterococcus faecalis; Fluconazole; Gram-Positive Bacterial Infections; Humans; Infant, Newborn; Kidney; Kidney Diseases; Sepsis; Treatment Outcome; Urinary Tract Infections; Urine; Vesico-Ureteral Reflux

Clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs) have been established for several Candida spp. and the newer triazoles and echinocandins but are not yet available for older antifungal agents, such as amphotericin B, flucytosine, or itraconazole. We determined species-specific ECVs for amphotericin B (AMB), flucytosine (FC) and itraconazole (ITR) for eight Candida spp. (30,221 strains) using isolates from 16 different laboratories in Brazil, Canada, Europe, and the United States, all tested by the CLSI reference microdilution method. The calculated 24- and 48-h ECVs expressed in μg/ml (and the percentages of isolates that had MICs less than or equal to the ECV) for AMB, FC, and ITR, respectively, were 2 (99.8)/2 (99.2), 0.5 (94.2)/1 (91.4), and 0.12 (95.0)/0.12 (92.9) for C. albicans; 2 (99.6)/2 (98.7), 0.5 (98.0)/0.5 (97.5), and 2 (95.2)/4 (93.5) for C. glabrata; 2 (99.7)/2 (97.3), 0.5 (98.7)/0.5 (97.8), and 05. (99.7)/0.5 (98.5) for C. parapsilosis; 2 (99.8)/2 (99.2), 0.5 (93.0)/1 (90.5), and 0.5 (97.8)/0.5 (93.9) for C. tropicalis; 2 (99.3)/4 (100.0), 32 (99.4)/32 (99.3), and 1 (99.0)/2 (100.0) for C. krusei; 2 (100.0)/4 (100.0), 0.5 (95.3)/1 (92.9), and 0.5 (95.8)/0.5 (98.1) for C. lusitaniae; -/2 (100.0), 0.5 (98.8)/0.5 (97.7), and 0.25 (97.6)/0.25 (96.9) for C. dubliniensis; and 2 (100.0)/2 (100.0), 1 (92.7)/-, and 1 (100.0)/2 (100.0) for C. guilliermondii. In the absence of species-specific CBP values, these wild-type (WT) MIC distributions and ECVs will be useful for monitoring the emergence of reduced susceptibility to these well-established antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Brazil; Canada; Candida; Candidiasis; Europe; Flucytosine; Humans; Itraconazole; Microbial Sensitivity Tests; United States

In recent years the incidence of bloodstream infections due to Candida species has progressively increased, partly due to the more critical conditions of hospitalized patients. There has been a significant increase in immune-compromised, diabetic and/or elderly patients, also with venous access, with a subsequent increase in Candida species isolated from bloodstream infections. In 2009-2010 in the hospitals of Mestre and Venice we isolated 123 Candida species from bloodstream infections: 59 Candida albicans, 28 Candida parapsilosis, 12 Candida glabrata, 9 Candida tropicalis, and 4 Geotrichum capitatum, while the 11 others belong to 8 different species. We calculated MIC for the following antifungal agents: fluconazole, itraconazole, voriconazole, 5-flucytosine, amphotericin B and caspofungin.

Topics: Amphotericin B; Antifungal Agents; Blood; Candida; Candidiasis; Caspofungin; Drug Resistance, Fungal; Echinocandins; Fluconazole; Flucytosine; Hospitals; Humans; In Vitro Techniques; Itraconazole; Lipopeptides; Microbial Sensitivity Tests; Pyrimidines; Reproducibility of Results; Risk Factors; Triazoles; Voriconazole

Candida endocarditis is extremely rare in term neonates, and gall bladder involvement due to candidemia has never been reported amongst neonates and infants. A term, appropriate for gestational age neonate developed Candida tropicalis blood stream infection in second week of life. He was started on conventional amphotericin B. However, he failed to show any clinical improvement, and candidemia keep on persisting. Repeat sanctuary sites screening revealed multiple echogenic masses in heart (vegetations) and gall bladder. On changing the treatment to liposomal amphotericin B and fluconazole, he recovered clinically, echogenic masses in gall bladder disappeared, and intracardiac vegetations decreased in size.

Topics: Amphotericin B; Antifungal Agents; Candida tropicalis; Candidiasis; Endocarditis; Fluconazole; Gallbladder Diseases; Humans; Infant, Newborn; Male

The occurrence of endogenous Candida endophthalmitis is rare in immunocompetent patients. We report a case of a 29-year-old healthy woman who developed endogenous Candida endophthalmitis after normal spontaneous vaginal delivery. The patient was diagnosed with Candida endophthalmitis by positive vitreous culture obtained by diagnostic vitrectomy. After vitrectomy, she was treated with systemic and intravitreal antifungal therapy, and subsequently, her visual acuity recovered to 20/20 without other complications. Normal spontaneous vaginal delivery may cause endogenous Candida endophthalmitis in young healthy women. Diagnostic vitrectomy with systemic and intravitreal antifungal treatment can be useful in diagnosis and treatment of Candida endophthalmitis.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Endophthalmitis; Female; Fluconazole; Humans; Intravitreal Injections; Postpartum Period

Spondylodiscitis is an inflammatory disease, usually infectious, of one or more vertebral bodies and of corresponding intervertebral discs. The fungal aetiology is rare (less than 5% of cases), affecting mostly immunocompromised individuals. It is often a delayed diagnosis by the indolence of symptoms, presenting itself as a serious infection, which may result in important functional consequences. The authors present the case of a 75-year-old male, with constitutional complaints and intense back pain. Prior recent history of left hemicolectomy due to diverticulitis with multiple surgical complications, resulted in prolonged intensive care unit hospitalisation, and, later on, an episode of fungal endophthalmitis. The diagnosis of spondylodiscitis L5/S1 was performed by MRI. The patient underwent surgical disco-vertebral debridement and isolation of a Candida albicans was seen in the collected surgical material. No evidence of an immunossupressive status was found. Treatment was complemented with liposomal amphotericin B in the maximum recommended dose.

Topics: Aged; Amphotericin B; Antifungal Agents; Candidiasis; Combined Modality Therapy; Debridement; Diagnosis, Differential; Discitis; Endophthalmitis; Humans; Magnetic Resonance Imaging; Male

Liposomal amphotericin B (LAMB) is frequently administered in NICU to preterm infants <1500 g at birth (VLBW) for treatment of systemic fungal infections (SFI). Concerns exist on safety and tolerability of such drug in patients who are at risk for renal function impairment due to their prematurity.. To assess the occurrence of renal function impairment related to LAMB in a 10-year cohort of VLBW neonates treated with this drug.. Through database search of clinical charts, all VLBW neonates admitted to a 3(rd) level NICU in the years 1998-2007 and undergoing treatment with LAMB were identified. The occurrence of LAMB-attributable renal toxicity was investigated; infants withdrawn from treatment for development of adverse effects or toxicity were identified.. In the study period, 71 of 792 admitted VLBW neonates (8.9%) underwent antifungal treatment with LAMB administered at the recommended dosages (3-to-5 mg/kg/day). Mean duration of treatment was 14 (±9) days, mean cumulative dose given was 58 (±25) mg/kg per infant. Renal compromise, defined as hypokalaemia, and/or elevated creatinine serum levels, and/or decreased urine output, occurred in 2 of 71 (2.8%) treated patients, by 5 (±3) mean days after treatment initiation. In both patients LAMB was withdrawn; renal function impairment was only mild and transient, and normal renal function was restored at discharge. No other significant adverse effects were recorded in any treated neonate.. LAMB is generally safe and well tolerated in VLBW neonates. The occurrence of LAMB-related nephrotoxicity appears to be uncommon, mild and transient.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cohort Studies; Creatinine; Fluconazole; Humans; Hypokalemia; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Kidney; Kidney Diseases; Kidney Function Tests; Mycoses; Premature Birth; Retrospective Studies; Sepsis

The presence of Candida in urine presents a therapeutic challenge for the physician as it is often asymptomatic, and management guidelines have not been clearly laid down on this issue. The presence of Candida in urine may represent contamination of clinical sample, actual colonization of the lower urinary tract or may be a true indicator of invasive infection of lower and/or upper urinary tract. In a clinical setting like the ICU, multiple risk factors for Candida colonization may be present in the same patient, thereby increasing the chances of candiduria, manifold. In the present study on 80 patients in ICU, high rate of Candida colonization (57.5%) was found in urine samples of ICU patients with C. tropicalis (57.3%) being the predominant species. We also isolated 8 strains of Trichosporon species, all of these presented as a mixed infection along with Candida species. Among the various risk factors studied, urinary catheterization and previous antibiotic therapy were identified as statistically significant (P value <0.05). The minimum inhibitory concentration of the isolates was determined for amphotericin B, fluconazole and itraconazole by E-test. Most of the isolates were susceptible to amphotericin B. The C. parapsilosis strains did not show any drug resistance; however, resistance to fluconazole was observed 18.6, 27.27, 50 and 25% in C. tropicalis, C. albicans, C. glabrata and Trichosporon species, respectively.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Female; Fluconazole; Humans; Intensive Care Units; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Risk Factors; Trichosporon; Trichosporonosis; Urine; Young Adult

To compare in vitro susceptibility of amphotericin B (AMB) and amphotericin B methyl ester (AME) (a more soluble and less toxic formulation of AMB) against Candida albicans isolates recovered from human cases of endophthalmitis.. The in vitro susceptibility of AMB and AME was determined for C. albicans isolates recovered from endophthalmitis (N=10) and for C. albicans ATCC reference strain 90028 using the Clinical and Laboratory Standards Institute M27-A2 (NCCLS/CLSI) broth dilution method. All isolates were obtained from samples of vitreous humor of patients with suspected endophthalmitis within the last 5 years at the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine (Miami, FL).. The minimal inhibitory concentrations (MICs) of AME were equal to or lower than values for AMB in 7 of the 10 isolates; range: AME (0.125-1 μg/mL) versus (0.5-1 μg/mL) for AMB. The MIC(90) value of both drugs was equal (1 μg/mL). Compared with AMB, the minimal fungicidal concentrations (MFCs) of AME were equal to or lower in 8 of 10 isolates; range: AME (0.125-2 μg/mL) versus AMB (0.25-4 μg/mL). MFC(90) values of AME (1 μg/mL) was slightly superior to AMB (2 μg/mL). The MIC of the quality control strain (ATCC(®) 90028) was within an acceptable range.. AME was equivalent to AMB in vitro against C. albicans. This formula may offer a slightly more efficient and less toxic formulation for the treatment of Candida endophthalmitis.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Endophthalmitis; Eye Infections, Fungal; Humans; Microbial Sensitivity Tests; Solubility; Vitreous Body

Lung transplant recipients are at high risk of invasive fungal disease (IFD), particularly invasive aspergillosis and candidiasis. The antifungal strategy that optimally balances effective reduction of IFD with a minimum of toxicity remains undefined; universal triazole prophylaxis is common at lung transplantation (LT) centers, despite the well-known toxicities and costs of this approach.. We implemented an antifungal strategy in March 2007 targeted at LT recipients at highest risk for IFD based on our institutional epidemiology. All patients received inhaled amphotericin B during their initial LT hospitalization, bilateral lung transplant recipients received 7 to 10 days of micafungin, and only patients with growth of yeast or mold in their day-of-transplant cultures received further oral antifungal therapy tailored to their fungal isolate.. IFD events were assessed in sequential cohorts composed of 82 lung transplant recipients before and 83 patients after the implementation of this targeted antifungal strategy. We observed a sharp decline in IFD; in the second cohort, 87%, 91%, and 96% of patients were free of IFD, invasive candidiasis, and invasive aspergillosis at 1 year. Only 19% of patients in the second cohort received systemic antifungal therapy beyond the initial LT hospitalization, and no patients experienced antifungal drug-related toxicity or IFD-associated mortality.. The targeted antifungal strategy studied seems to be a reasonable approach to reducing post-LT IFD events while limiting treatment-related toxicities and costs.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Cohort Studies; Echinocandins; Female; Humans; Lipopeptides; Lung Transplantation; Male; Micafungin; Middle Aged; Mycoses; Risk; Time Factors; Triazoles

To investigate the correlation between in vitro killing activity and in vivo efficacy of micafungin (MCFG) and liposomal amphotericin B (L-AMB) against Candida tropicalis in a neutropenic murine lethal infection model.. Candida albicans (one strain) and C. tropicalis (three strains) were tested in time-kill studies. Cyclophosphamide-treated mice were inoculated intravenously with each strain. One day after inoculation, antifungals were administered intravenously once daily for 1 or 3 days.. MCFG exhibited fungicidal activity against C. albicans ATCC 90029 and C. tropicalis SP-20142, and fungistatic activity against C. tropicalis ATCC 42678 and SP-20047. The ED(50)s (dosage that results in 50% survival) of MCFG for C. tropicalis ATCC 42678 and SP-20047 (4.1-50 mg/kg) were higher than those for other strains (1.6-12 mg/kg). A 1-day course of MCFG was not effective against C. tropicalis ATCC 42678 and SP-20047 at the clinical dose (5 mg/kg), which achieved an AUC level almost equal to that of 100 mg in humans, whereas a 3-day course of 5 mg/kg MCFG was efficacious against all strains. In contrast, L-AMB showed fungicidal activity against all strains tested and the ED(50)s of L-AMB were 0.08-0.65 mg/kg. In both treatment regimens, the minimum effective doses of L-AMB (≤0.5 mg/kg) were less than the clinical dosage (≤5 mg/kg).. The in vivo efficacy of MCFG and L-AMB showed a correlation with the in vitro killing activity. At the clinical dose, L-AMB exerted anti-C. tropicalis activity within a shorter treatment period than MCFG.

Topics: Amphotericin B; Animals; Antifungal Agents; Area Under Curve; Candida tropicalis; Candidiasis; Disease Models, Animal; Echinocandins; Lipopeptides; Male; Micafungin; Mice; Microbial Sensitivity Tests; Neutropenia

Topics: Amphotericin B; Antifungal Agents; beta-Glucans; Biofilms; Biomarkers; Candida; Candidiasis; Catheterization, Central Venous; Drug Resistance, Fungal; Humans; Liposomes

The Sensititre YeastOne (SYO) method is a widely used method to determine the susceptibility of Candida spp. to antifungal agents. CLSI clinical breakpoints (CBP) have been reported for antifungals, but not using this method. In the absence of CBP, epidemiological cutoff values (ECVs) are useful to separate wild-type (WT) isolates (those without mechanisms of resistance) from non-WT isolates (those that can harbor some resistance mechanisms), which is the goal of any susceptibility test. The ECVs for five agents, obtained using the MIC distributions determined by the SYO test, were calculated and contrasted with those for three statistical methods and the MIC(50) and modal MIC, both plus 2-fold dilutions. The median ECVs (in mg/liter) (% of isolates inhibited by MICs equal to or less than the ECV; number of isolates tested) of the five methods for anidulafungin, micafungin, caspofungin, amphotericin B, and flucytosine, respectively, were as follows: 0.25 (98.5%; 656), 0.06 (95.1%; 659), 0.25 (98.7%; 747), 2 (100%; 923), and 1 (98.5%; 915) for Candida albicans; 8 (100%; 352), 4 (99.2%; 392), 2 (99.2%; 480), 1 (99.8%; 603), and 0.5 (97.9%; 635) for C. parapsilosis; 1 (99.2%; 123), 0.12 (99.2%; 121), 0.25 (99.2%; 138), 2 (100%; 171), and 0.5 (97.2%; 175) for C. tropicalis; 0.12 (96.6%; 174), 0.06 (96%; 176), 0.25 (98.4%; 188), 2 (100%; 209), and 0.25 (97.6%; 208) for C. glabrata; 0.25 (97%; 33), 0.5 (93.9%; 33), 1 (91.9%; 37), 4 (100%; 51), and 32 (100%; 53) for C. krusei; and 4 (100%; 33), 2 (100%; 33), 2 (100%; 54), 1 (100%; 90), and 0.25 (93.4%; 91) for C. orthopsilosis. The three statistical methods gave similar ECVs (within one dilution) and included ≥ 95% of isolates. These tentative ECVs would be useful for monitoring the emergence of isolates with reduced susceptibility by use of the SYO method.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Echinocandins; Flucytosine; Humans; Microbial Sensitivity Tests; Models, Statistical; Mycology

Two novel isolates of Candida glabrata exhibiting reduced sensitivity to amphotericin B (MIC, 8 μg ml(-1)) were found to be ERG2 mutants, wherein Δ(8)-sterol intermediates comprised >90% of the total cellular sterol fraction. Both harbored an alteration at Thr(121) in ERG2; the corresponding residue (Thr(119)) in Saccharomyces cerevisiae is essential for sterol Δ8-Δ7 isomerization. This constitutes the first report of C. glabrata harboring mutations in ERG2 and exhibiting reduced sensitivity to amphotericin B.

Topics: Amino Acid Sequence; Amphotericin B; Antifungal Agents; Azoles; Candida glabrata; Candidiasis; Drug Resistance, Fungal; Fluconazole; Fungal Proteins; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Pyrimidines; Saccharomyces cerevisiae; Steroid Isomerases; Sterols; Triazoles; Voriconazole

The in vitro antifungal susceptibility of 636 Candida bloodstream isolates collected from 15 tertiary hospitals in Korea was determined using the Vitek-2 yeast susceptibility system (bioMérieux, France). Overall susceptibility rates were 98.1%, 95.9%, 99.1%, and 97.3% for amphotericin B, fluconazole, voriconazole, and flucytosine, respectively. The results show that the rates of resistance to 4 antifungal drugs remain low among Candida bloodstream isolates in Korea.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Fluconazole; Flucytosine; Humans; Microbial Sensitivity Tests; Pyrimidines; Republic of Korea; Tertiary Care Centers; Triazoles; Voriconazole

To explore the management of fungal pyelonephritis in infants.. Data from 5 cases with fungal pyelonephritis, including the clinical situation, laboratory examination, feature of imaging, and treatment were analyzed.. All the 5 cases were preterm and low birth weight infants. In 3 cases the disease was unilateral, in 2 cases were bilateral, and acute renal failure occurred. Fungus balls presented on imaging. Urine culture was positive of Candida albicans. Treatment with percutaneous nephrostomy, irrigation and antifungal agent were associated with good prognosis. Only 1 case died. The surviving patients were followed up for 10 - 20 months and the results showed normal growth and development. B-mode ultrasound examination did not show any malformation of the urinary system.. Fungal pyelonephritis was commom in preterm infants. Candida albicans was the major pathogenic microorganism. Percutaneous nephrostomy and drainage were effective in patients with urinary obstruction in relief of obstruction, early diagnosis and control of infection.

Topics: Acute Kidney Injury; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Chymotrypsin; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Male; Nephrostomy, Percutaneous; Pyelonephritis; Treatment Outcome; Ultrasonography, Doppler, Color; Ureteral Obstruction; Urine

During recent decades, there has been a change in the epidemiology of Candida infections, characterized by a progressive shift from a predominance of Candida albicans to non-albicans Candida species. This study was undertaken to analyze the change in the epidemiology of candidaemia and antifungal use at tertiary care hospital in New Delhi, India, over a period of 10 years.. A retrospective review of candidaemia between 1999 and 2008 and antifungal use from 2000 to 2008 was performed at Sir Ganga Ram Hosptial, New Delhi. Initially (1999-2005), isolates were differentiated as C. albicans and non- albicans Candida species. Between 2006-2008, these were identified to the species level and antifungal susceptibility was performed.. The occurrence of candidaemia and total antifungal use increased significantly. Candidaemia due to non-albicans species increased and this was correlated with an increasing use of fluconazole. There was emergence and increased isolation of a novel species C. haemulonii with decreased susceptibility to both amphotericin B and azoles. Overall, sensitivities of 89.6, 90.9, 88.6, 68.8 and 54.3 per cent to amphotericin B, 5 flucytosine, voriconazole, fluconazole and itraconazole, respectively were observed. Cross-resistance or reduced susceptibility to both fluconazole (MIC >16 μg/ml) and voriconazole was observed in 11.3 per cent isolates.. The study demonstrates a shift to non-albicans Candida species causing fungaemia and the emergence of amphotericin B and azole resistant novel species, C. haemulonii. Decreased susceptibility to fluconazole, as well as the threat of emergence of cross-resistance to voriconazole in the background of high azole consumption may limit the use of these agents as a presumptive therapy for Candida blood stream infections (BSI).

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; Fluconazole; Flucytosine; Humans; Incidence; India; Itraconazole; Microbial Sensitivity Tests; Pyrimidines; Retrospective Studies; Tertiary Care Centers; Triazoles; Voriconazole

Substitution around 5-methyl benzothieno[3,2-b]quinolinium (2) ring system was explored in order to identify positions of substitution that could improve its antifungal profile. The 3-methoxy (10b) was active against C. albicans, C. neoformans, and A. fumigatus and the 4-chloro (10f) analog showed moderate increases in anti-cryptococcal and anti-aspergillus activities. The effectiveness of 10b and 10f were validated in murine models of candidiasis and cryptococcosis, respectively. The efficacy of 10f in reducing brain cryptococcal infection and its observation in the brain of mice injected with this quaternary compound confirm the capacity of these compounds to cross the blood-brain barrier of mice. Overall, several of the chloro and methoxy substituted compounds showed significant improvements in activity against A. fumigatus, the fungal pathogen prevalent in patients receiving organ transplant. Opening the benzothiophene ring of 2 to form 1-(5-cyclohexylpentyl)-3-(phenylthio)quinolinium compound (3) resulted in the identification of several novel compounds with over 50-fold increases in potency (cf. 2) while retaining low cytotoxicities. Thus, compound 3 constitutes a new scaffold for development of drugs against opportunistic infections.

Topics: Animals; Blood-Brain Barrier; Candidiasis; Chromatography, High Pressure Liquid; Disease Models, Animal; Fungi; In Vitro Techniques; Magnetic Resonance Spectroscopy; Maximum Tolerated Dose; Mice; Microbial Sensitivity Tests; Quinolines

Therapy-related acute myelogenous leukemia (t-AML) is a generally fatal disease with a very poor response to conventional chemotherapy. Allogeneic stem cell transplantation (allo-SCT) has been reported in patients with chemotherapy- responsive t-AML. However its use is limited owing to complications from previous treatments. Nonmyeloablative conditioning provides rapid hematologic engraftment and it is a feasible option for patients who are at increased risk for conventional SCT. There are few data on their use in patients with t-AML. We describe the case of a boy who developed visceral fungal infection with liver abscesses after induction chemotherapy for t-AML. He received allo-SCT with a nonmyeloablative regimen, plus amphotericin B during the transplant procedure. The patient is alive and free of both leukemia and fungal infection 2 years after allo-SCT. Nonmyeloablative allo-SCT may provide durable remission in patients with t-AML, preexisting invasive fungal infections, and a high risk of adverse effects from standard chemotherapy and prolonged cytopenia, without resurgence of the fungal infection.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Candidiasis; Child; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Transplantation, Homologous; Treatment Outcome

The aim of this pharmaco-epidemiological study was to evaluate the prevalence of oropharyngeal candidiasis (OPC) in cancer patients treated with chemotherapy and/or radiotherapy.. Signs and symptoms of OPC were noted for all patients. Antifungal therapeutic management was recorded in OPC patients. Patients receiving local antifungal treatments were monitored until the end of treatment.. Enrolled in the study were 2,042 patients with solid tumor and/or lymphoma treated with chemotherapy and/or another systemic cancer treatment and/or radiotherapy. The overall prevalence of OPC was 9.6% (95% confidence interval, 8.4%-11.0%] in this population. It was most frequent in patients treated with combined chemoradiotherapy (22.0%) or with more than two cytotoxic agents (16.9%). Local antifungal treatments were prescribed in 75.0% of OPC patients as recommended by guidelines. The compliance to treatment was higher in patients receiving once-daily miconazole mucoadhesive buccal tablet (MBT; 88.2%) than in those treated with several daily mouthwashes of amphotericin B (40%) or nystatin (18.8%).. OPC prevalence in treated cancer patients was high. Local treatments were usually prescribed as per guidelines. Compliance to local treatments was better with once-daily drugs.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candidiasis; Candidiasis, Oral; Female; France; Humans; Male; Middle Aged; Neoplasms; Oropharynx; Pharyngeal Diseases; Young Adult

We present a case of a patient with preoperative cutaneous candidiasis, who developed candidal infection during stage revision knee arthroplasty. The patient received intravenous fluconazole for 6 weeks and resection arthroplasty with an amphotericin B-loaded cement spacer and continuous oral fluconazole therapy for 9 weeks. Revision surgery was successful.

Topics: Administration, Oral; Aged; Amphotericin B; Antifungal Agents; Arthritis, Infectious; Arthroplasty, Replacement, Knee; Bone Cements; Candidiasis; Fluconazole; Humans; Infusions, Parenteral; Knee Joint; Knee Prosthesis; Male; Prosthesis-Related Infections; Radiography; Reoperation

To construct a suitable ex vivo model for the research of molecular mechanisms and the pharmacological screening of fungal adherence on the corneal surface.. Mouse eyes were divided into three groups as follows: a control group with normal corneal epithelium, a group with corneal epithelium that was needle-scarified, and a group with corneal epithelium that was completely debrided. All 96 corneas were placed in organ culture and inoculated with 5 μl spore suspensions of Candida albicans at 10⁹, 10⁸, or 10⁷ colony-forming units (CFU)/ml and incubated for 0, 30, 60, or 120 min. The corneas were homogenated and diluted for quantification by counting the CFU. The effects of amphotericin B or chondroitin sulfate on the adherence of the fungal spores were evaluated with the ex vivo organ culture model and were also compared with the human corneal epithelium monolayer model in vitro.. Compared with the normal corneas with intact epithelium, the corneas with scarified and debrided epithelium adhered more spores for above two and four folds. The spore adhesion on the corneal surface was in an inoculation concentration- and incubation time-dependent manner. Moreover, both amphotericin B and chondroitin sulfate inhibited the adhesion of C. albicans spores on the corneal surface, but the inhibitory rates were different between the ex vivo corneal organ culture model and the in vitro corneal epithelium monolayer model.. The corneal organ culture was a suitable ex vivo model for the research of fungal adhesion mechanisms and drug screening.

Topics: Amphotericin B; Animals; Bacterial Adhesion; Candida albicans; Candidiasis; Chondroitin Sulfates; Colony Count, Microbial; Cornea; Corneal Injuries; Corneal Ulcer; Disease Models, Animal; Eye Infections, Fungal; Mice; Mice, Inbred BALB C; Organ Culture Techniques; Time Factors

Candida haemulonii, one of the non-albicans Candida species, is an emerging yeast pathogen that is known to be resistant to amphotericin B and other antifungal agents such as azoles. These anti-fungal agents have often been associated with clinical treatment failure, so no treatment regimen has been clearly established for invasive C. haemulonii infections. We investigated a catheter-related infection of C. haemulonii candidemia in an adult patient in long-term hospital care. In the early stages, the candidemia remained persistent despite treatment with fluconazole. However, after changing the antifungal agent to caspofungin, the candidemia was resolved. Fluconazole and amphotericin B are not reliable empirical antifungal agents for invasive C. haemulonii infections, as shown in previous case reports. An echinocandin such as caspofungin may be an appropriate empirical choice of antifungal agent for an invasive C. haemulonii infection.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Catheter-Related Infections; Echinocandins; Fluconazole; Hospitals; Humans; Lipopeptides; Long-Term Care; Male; Phylogeny

The aims of this study were to analyse the amphotericin B and fluconazole susceptibility and molecular epidemiology of Candida strains (Candida albicans, Candida tropicalis and Candida glabrata) isolated from the urine samples of patients hospitalized in the intensive care unit. Identification of the isolates was done according to microscopic morphology (chlamydospor, blastospor, pseudohyphae and true hyphae) on cornmeal agar, germ tube formation and carbohydrate assimilation patterns (API ID 32C bioMérieux, France). Antifungal susceptibilities of the isolates were determined by in vitro broth microdilution method recommended by Clinical and Laboratory Standards Institute (CLSI). To investigate the clonal relationship of the isolates, randomly amplified polymorphic DNA (RAPD) analysis was performed by using Cnd3 primer. Of the 56 Candida isolates minimum inhibitory concentration (MIC) ranges, MIC50 and MIC90 values for amphotericin B were 0.125-1 µg/ml, 0.125 and 0.5 µg/ml for C.albicans, 0.125-1 µg/ml, 0.25 and 1 µg/ml for C.tropicalis and 0.125-1 µg/ml, 0.25 and 1 µg/ml for C.glabrata, respectively. Fluconazole MIC ranges, MIC50 and MIC90 values were 0.25-4 µg/ml, 0.25 and 0.5 µg/ml for C.albicans, 0.25-16 µg/ml, 0.5 and 1 µg/ml for C.tropicalis and 0.5-64 µg/ml, 8 and 16 µg/ml for C.glabrata, respectively. For amphotericin B, none of the isolates had high MIC values (MIC > 1 µg/ml). While one of the C.glabrata isolates was resistant to fluconazole (MIC ≥ 64 µg/ml), one C.tropicalis and two C.glabrata isolates were dose-dependent susceptible (MIC: 16-32 µg/ml). The results of RAPD analysis indicated an exogenous spread from two clones for C.albicans, one clone for C.glabrata and one clone for C.tropicalis. This study underlines the importance of molecular epidemiological analysis of clinical samples together with hospital environmental samples in terms of Candida spp. To determine the exogenous origin for the related strains and to prevent nosocomial Candida infections.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; DNA, Fungal; Female; Fluconazole; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Molecular Epidemiology; Random Amplified Polymorphic DNA Technique; Turkey; Urinary Tract Infections; Urine

Currently, there has been an increased frequency of fungal infections. Candida albicans and other Candida spp. have been proven to be major causes for urinary tract infection. Increased resistance to antifungals indicates the need to develop strategies in order to prevent the spread of resistance. Chromogenic medium have been proven to be useful in the detection of yeasts in clinical specimens containing mixed cultures of Candida. The aim of this study was to compare the results of antifungal susceptibility testing with fluconazole and amphotericin B on strains of Candida spp. isolated from urine, conducted on a Mueller-Hinton Agar with Glucose and Methylene Blue (MHAGMB) medium and on a Hicrome Candida® Agar with 2% Glucose (HCAG) medium. We used 40 samples of Candida spp. isolated from urine samples from inpatients and outpatients. The results showed that both media presented high rates of agreement, above 94%. The use of the HCAG medium decreases the release time of the results by 24-48 h, which may be decisive for initiating the correct drug treatment.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Culture Media; Fluconazole; Humans; Microbial Sensitivity Tests; Urine

The antifungal activity of amphotericin B (AmB) incorporated in three cholesteryl carbonate esters (CCEs), sodium cholesteryl carbonate, cholesteryl palmityl carbonate, and dicholesteryl carbonate, was examined to assess their potential for use in a dry powder aerosol. Formulations containing dissolved AmB were stable for 6 months. The particle size varied inversely with liquid crystalline content with observed mass median aerodynamic diameters ranging from 4 to 8 μ m. This was consistent with the visual appearance of the liquid crystals as being low density and free flowing at room temperature. When dispersed in water, the presence of the CCE reduced the rate and extent of AmB release, consistent with the estimated liquid crystal/water partition coefficient. Nevertheless, the rate of AmB release was always sufficient to kill the fungus as established with bioactivity studies. AmB formulated with CCE as a dry powder appears to be promising for use in treating lung fungal infections.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Carbonates; Cholesterol Esters; Cryptococcosis; Cryptococcus neoformans; Drug Stability; Humans; Particle Size; Solubility

This study aimed to determine the frequency of invasive fungal infection (IFI) in pediatric patients with hematologic malignancy who received amphotericin B oral suspension and early intravenous fluconazole during the neutropenic phase as prophylaxis for IFI. Records of 743 neutropenic episodes induced by cytotoxic chemotherapy between 1997 and 2008 were retrospectively reviewed to determine risk factors for and frequency of IFI. The overall frequency of IFI was 0.8% (n=6) and frequencies of proven, probable, and possible infections were 0.3% (n=2), 0.4% (n=3), and 0.1% (n=1), respectively. During 351 episodes of profound neutropenia (neutrophil count <500/μL for ≥ 14 d), overall incidence of IFI was 1.71% (n=6). Pulmonary aspergillosis was the most common causative agent, and no patients showed candidemia, or hepatosplenic candidiasis. Cytotoxic chemotherapy regimens for acute myelogenous leukemia and profound neutropenia were significantly associated with IFI (P=0.004 and P=0.009, respectively). No IFI-attributable deaths or breakthrough fungal infections occurred. Our results indicate that amphotericin B oral solution and early intravenous fluconazole may be effective in reducing the incidence and mortality of IFI in pediatric patients with hematologic malignancies.

Topics: Administration, Oral; Adolescent; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Candidiasis; Child; Child, Preschool; Female; Fluconazole; Humans; Incidence; Infant; Infusions, Intravenous; Leukemia, Myeloid, Acute; Male; Neutropenia; Retrospective Studies; Risk Factors; Treatment Outcome

In many instances a report from the clinical laboratory indicating candiduria represents colonization or procurement contamination of the specimen and not invasive candidiasis. Even if infection of the urinary tract by Candida species can be confirmed, antifungal therapy is not always warranted. Further investigation may reveal predisposing factors, which if corrected or treated, result in the resolution of the infection. For those with symptomatic urinary tract infections (UTIs), the choice of antifungal agent will depend upon the clinical status of the patient, the site of infection, and the pharmacokinetics and pharmacodynamics of the agent. Because of its safety, achievement of high concentrations in the urine, and availability in both an oral and intravenous formulation, fluconazole is preferred for the treatment of Candida UTIs. Flucytosine is concentrated in urine and has broad activity against Candida spp, but its use requires caution because of toxicity. Low-dose amphotericin B may be useful for Candida UTIs in selected patients. The role of echinocandins and azoles that do not achieve measurable concentrations in the urine is not clear. Small case series note some success, but failures have also occurred. Irrigation of the bladder with antifungal agents has limited utility. However, with fungus balls, irrigation of the renal pelvis through a nephrostomy tube can be useful in combination with systemic antifungal agents.

Topics: Algorithms; Amphotericin B; Antifungal Agents; Azoles; Candida; Candidiasis; Candidiasis, Invasive; Causality; Echinocandins; Fluconazole; Flucytosine; Humans; Urinary Tract Infections

Systemic candidiasis causes significant mortality in patients despite amphotericin B (AMB) therapy. Mycograb C28Y variant, a human recombinant antibody fragment to heat shock protein 90, is closely related to Mycograb, which showed a survival advantage in combination with AMB in a phase III human trial. The Mycograb C28Y variant could potentially increase the antifungal effect of AMB. In our study, the interaction between AMB-desoxycholate (DAMB) and the Mycograb C28Y variant was characterized in vitro by using a checkerboard method. Quantitative cultures of kidneys, livers, and spleens of neutropenic mice with systemic Candida albicans infections were used to assess the in vivo interaction between 1.4 mg/kg of body weight/day of DAMB and 0.15, 1.5, and 15 mg/kg/day of the Mycograb C28Y variant after 1, 3, and 5 days of therapy. DAMB and Mycograb C28Y variant monotherapies, vehicle, and a no-treatment arm served as controls. Also, single- and multidose pharmacokinetics for the Mycograb C28Y variant were determined. Indifference or synergy between DAMB and the Mycograb C28Y variant was seen in two trials by the checkerboard method. The pharmacokinetics of the Mycograb C28Y variant was best described by a 2-compartment model with a median serum t(1/2)(α) of ~0.198 h and a t(1/2)(β) of ~1.77 h. In mice, DAMB together with the Mycograb C28Y variant was no more effective than AMB alone (P > 0.05 by analysis of variance). The Mycograb C28Y variant alone had no antifungal activity. We therefore conclude that the Mycograb C28Y variant in combination with DAMB offered no benefit over DAMB monotherapy in a neutropenic murine model of systemic candidiasis.

Topics: Amphotericin B; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antifungal Agents; Candidiasis; Deoxycholic Acid; Drug Combinations; Female; HSP90 Heat-Shock Proteins; Humans; Mice; Microbial Sensitivity Tests

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Child; Echinocandins; Humans; Ketoconazole; Mycoses; Prognosis; Treatment Outcome

Intensified chemotherapy and hematopoietic stem cell transplantation result in severe and prolonged granulocytopenia with an increased risk of invasive fungal infections. The major fungal species that cause serious infections in cancer patients are Candida species and Aspergillus species. The main features of Candida infection in this context are oropharyngeal candidiasis and Candida esophagitis, chronic disseminated candidiasis, also known as hepatosplenic candidiasis, and candidemia. Aspergillus can cause severe lung infection but also sinusal or CNS infection. Because invasive fungal infections are severe and often life-threatening, preventive and empirical managements have become standard practice. An increasing number of antifungal drugs is now available, notably lipid formulations of amphotericin B (liposomal amphotericin B), new azoles with broad spectrum of activity and echinocandin.

Topics: Agranulocytosis; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Azoles; Candidiasis; Child; Cryptococcosis; Echinocandins; Humans; Mycoses; Neoplasms; Opportunistic Infections; Risk Factors; Stem Cell Transplantation; Treatment Outcome

Candida is an important cause of bloodstream infections (BSI), causing significant mortality and morbidity in health care settings. From January 2008 to December 2010 all consecutive patients who developed candidemia at San Martino University Hospital, Italy were enrolled in the study. A total of 348 episodes of candidaemia were identified during the study period (January 2008-December 2010), with an incidence of 1,73 episodes/1000 admissions. Globally, albicans and non-albicans species caused around 50% of the cases each. Non-albicans included Candida parapsilosis (28.4%), Candida glabrata (9.5%), Candida tropicalis (6.6%), and Candida krusei (2.6%). Out of 324 evaluable patients, 141 (43.5%) died within 30 days from the onset of candidemia. C. parapsilosis candidemia was associated with the lowest mortality rate (36.2%). In contrast, patients with C. krusei BSI had the highest mortality rate (55.5%) in this cohort. Regarding the crude mortality in the different units, patients in Internal Medicine wards had the highest mortality rate (54.1%), followed by patients in ICU and Hemato-Oncology wards (47.6%).This report shows that candidemia is a significant source of morbidity in Italy, with a substantial burden of disease, mortality, and likely high associated costs. Although our high rates of candidemia may be related to high rates of BSI in general in Italian public hospitals, reasons for these high rates are not clear and warrant further study. Determining factors associated with these high rates may lead to identifying measures that can help to prevent disease.

Topics: Aged; Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Communicable Disease Control; Cross Infection; Echinocandins; Female; Fluconazole; Hospitals; Humans; Italy; Itraconazole; Lipopeptides; Male; Middle Aged; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole

The European Committee on Antimicrobial Susceptibility Testing-Subcommittee on Antifungal Susceptibility Testing (EUCAST-AFST) has determined breakpoints for amphotericin B for Candida spp. This Technical Note is based on the EUCAST amphotericin B rationale document (available on the EUCAST website: http://www.eucast.org). Species-specific breakpoints for C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis are S: MIC ≤1 mg/L, R: MIC > 1 mg/L. There are insufficient data to set breakpoints for other species. The breakpoints are based upon pharmacokinetic data, epidemiological cut-ff values and clinical experience. Breakpoints will be reviewed regularly.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Humans; Microbial Sensitivity Tests

We observed morphological manifestation of encephalitis 3, 7, 10 and 28 days after intravenous infection of adult male CBA mice with Candida albicans. Compounds were administered intraperitoneally every other day starting from the next day postinfection. Untreated animals (100%) died over the period between days 18 and 20 postinfection; 60% animals receiving oxidized dextran alone survived by day 28 of observation. All animals treated with amphotericin B and composition of amphotericin B and oxidized dextran survived. On day 3 postinfection, the count of macrophage infiltrates and granulomas in the cerebral interstitium of mice treated with amphotericin B was equal to that in untreated mice, but was sufficiently lower in animals treated with the composition or oxidized dextran alone. On day 10, this index was similar in all groups and was approximately 5 times lower than in untreated animals on day 3. On day 28, macrophage infiltrates and granulomas were absent in the brain of all treated mice. These data suggest that oxidized dextran produced a therapeutic effect, which manifested earlier than the effect of amphotericin B and potentiated its effect, probably due to its competition with Candida albicans for mannose receptors on the brain-blood barrier endothelium.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Candida albicans; Candidiasis; Cell Movement; Dextrans; Drug Synergism; Encephalitis; Granuloma; Macrophages; Male; Mice; Mice, Inbred CBA; Oxidation-Reduction; Survival Rate

Fungal biofilms produce a small number of persister cells which can tolerate high concentrations of fungicidal agents. Persisters form upon attachment to a surface, an important step in the pathogenesis of Candida strains. The periodic application of antimicrobial agents may select for strains with increased levels of persister cells. In order to test this possibility, 150 isolates of Candida albicans and C. glabrata were obtained from cancer patients who were at high risk for the development of oral candidiasis and who had been treated with topical chlorhexidine once a day. Persister levels were measured by exposing biofilms growing in the wells of microtiter plates to high concentrations of amphotericin B and plating for survivors. The persister levels of the isolates varied from 0.2 to 9%, and strains isolated from patients with long-term carriage had high levels of persisters. High-persister strains were isolated from every patient with Candida carriage of more than 8 consecutive weeks but from no patients with transient carriage. All of the high-persister isolates had an amphotericin B MIC that was the same as that for the wild type, indicating that these strains were drug-tolerant rather than drug-resistant mutants. Biofilms of the majority of high-persister strains also showed an increased tolerance to chlorhexidine and had the same MIC for this antimicrobial as the wild type. This study suggests that persister cells are clinically relevant, and antimicrobial therapy selects for high-persister strains in vivo. The drug tolerance of persisters may be a critical but overlooked component responsible for antimicrobial drug failure and relapsing infections.

Topics: Adult; Aged; Biofilms; Candida albicans; Candidiasis; Carrier State; Chlorhexidine; Dose-Response Relationship, Drug; Female; Genes, Fungal; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mouth; Mouthwashes; Mutation; Neoplasms; Young Adult

The synthesis, in vitro evaluation, and conformational study of a new series of small-size peptides acting as antifungal agents are reported. In a first step of our study we performed a conformational analysis using Molecular Mechanics calculations. The electronic study was carried out using Molecular electrostatic potentials (MEPs) obtained from RHF/6-31G calculations. On the basis of the theoretical predictions three small-size peptides, RQWKKWWQWRR-NH(2), RQIRRWWQWRR-NH(2), and RQIRRWWQW-NH(2) were synthesized and tested. These peptides displayed a significant antifungal activity against human pathogenic strains including Candida albicans and Cryptococcus neoformans. Our experimental and theoretical results allow the identification of a topographical template which can serve as a guide for the design of new compounds with antifungal properties for potential therapeutic applications against these pathogenic fungi.

Topics: Amino Acid Sequence; Animals; Antifungal Agents; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Models, Molecular; Mycoses; Peptides; Poecilia; Toxicity Tests, Acute

We describe the acquisition of flucytosine, azole, and caspofungin resistance in sequential Candida glabrata bloodstream isolates collected from a bone marrow transplant patient with clinical failure. Point mutations in C. glabrata FUR1 (CgFUR1) and CgFKS2 and overexpression of CgCDR1 and CgCDR2 were observed in resistant isolates.

Topics: Antifungal Agents; Azoles; Candida glabrata; Candidiasis; Caspofungin; Child; Drug Resistance, Fungal; Echinocandins; Female; Flucytosine; Fungal Proteins; Fungemia; Hematopoietic Stem Cell Transplantation; Humans; Lipopeptides; Microbial Sensitivity Tests; Point Mutation

A Candida glabrata calcineurin mutant exhibited increased susceptibility to both azole antifungal and cell wall-damaging agents and was also attenuated in virulence. Although a mutant lacking the downstream transcription factor Crz1 displayed a cell wall-associated phenotype intermediate to that of the calcineurin mutant and was modestly attenuated in virulence, it did not show increased azole susceptibility. These results suggest that calcineurin regulates both Crz1-dependent and -independent pathways depending on the type of stress.

Topics: Animals; Antifungal Agents; Base Sequence; Calcineurin; Candida glabrata; Candidiasis; DNA Primers; DNA, Fungal; Drug Resistance, Fungal; Female; Fungal Proteins; Genes, Fungal; Humans; In Vitro Techniques; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mutation; Opportunistic Infections; Transcription Factors; Virulence

T-2307, a novel arylamidine, has been shown to exhibit broad-spectrum in vitro and in vivo antifungal activities against clinically significant pathogens. In our preliminary studies, Candida glabrata exhibited significant trailing growth (partial inhibition of growth over an extended range of antifungal concentrations) in the presence of T-2307 when it was tested using the Clinical and Laboratory Standards Institute (CLSI) guidelines with 0.2% glucose and 48 h of incubation, making reading of the MIC difficult. In the present study, we attempted to attenuate trailing growth to avoid misreading of the MIC. On the basis of the hypothesis that T-2307 may inhibit the mitochondrial functions of cells, the carbon source or the glucose concentration in the medium was changed. The trailing growth of C. glabrata ATCC 90030 in the presence of T-2307 was attenuated as the concentration of glucose in the medium decreased to 0.1% or lower, and trailing growth was completely inhibited when glycerol was used. A susceptibility test using Alamar blue was performed to facilitate reading of the MIC without changing the composition of the medium and provided a clear MIC endpoint at 24 h. To investigate if T-2307 shows efficacy against trailing isolates in vivo, we evaluated the efficacy of T-2307 in a murine model of disseminated candidiasis caused by C. glabrata. T-2307 at 0.05 mg/kg of body weight/day significantly decreased the viable count in the kidneys compared to that for the control group (P < 0.05). It would be better to test the susceptibility of C. glabrata to T-2307 using modified media or Alamar blue to avoid misreading of the MIC due to the significant trailing growth.

Topics: Animals; Antifungal Agents; Candida glabrata; Candidiasis; Male; Mice; Microbial Sensitivity Tests; Molecular Structure

Topics: Amphotericin B; Antifungal Agents; Bioprosthesis; Candidiasis; Caspofungin; Drug Therapy, Combination; Echinocandins; Endocarditis; Heart Valve Prosthesis; Humans; Lipopeptides; Liposomes; Male; Middle Aged; Photosensitivity Disorders; Postoperative Complications; Prosthesis-Related Infections; Pyrimidines; Triazoles; Voriconazole

Candida albicans is no longer the only yeast involved in infectious disorders, as others, such as C. famata, commonly associated with foods as well as terrestrial and marine environments, are being recognized as potential emerging pathogens that cause human candidiasis. We investigated the interaction between C. famata and human epithelial cells using monolayer cultures and an engineered human oral mucosa (EHOM). C. famata was able to adhere to gingival epithelial cells but failed to adopt the hyphal form in the presence/absence of proteins. Interestingly, when cultured onto the engineered human oral mucosa (EHOM), C. famata formed a biofilm and invaded the connective tissue. When normal human gingival epithelial cells were put in contact with C. famata, they expressed high levels of Toll-like receptors (TLR)-2, -4, and -6, but not TLR-9 mARN. The upregulation of TLRs was paralleled by an increase of IL-1beta and TNFalpha, but not IFNgamma mARN expression, suggesting the involvement of specific pro-inflammatory cytokines (IL-1beta and TNFalpha) in the defense against infection with C. famata. The active role of epithelial cells in the innate immunity against C. famata infection was enhanced by their capacity to express high levels of human beta-defensin (HBD)-1, -2, and -3. The upregulation of pro-inflammatory cytokines and antimicrobial peptide expression may explain the growth inhibition of C. famata by the gingival epithelial cells. Overall results provide additional evidence of the involvement of C. famata in the activation of innate immunity and the contribution of human epithelial cells in local defenses against such exogenous stimulations as C. famata infections.

Topics: Amphotericin B; beta-Defensins; Biofilms; Candida; Candidiasis; Cell Adhesion; Cytokines; Epithelial Cells; Gene Expression Regulation; Gingiva; Humans; Hyphae; Inflammation Mediators; Microbial Sensitivity Tests; Microbial Viability; Mouth Mucosa; RNA, Messenger; Tissue Engineering; Toll-Like Receptors

Candida tropicalis has been reported to be one of the Candida species which is most likely to cause bloodstream and urinary tract infections in hospitalized patients. Accordingly, the aim of this study was to characterize the virulence of C. tropicalis by assessing antifungal susceptibility and comparing the expression of several virulence factors. This study was conducted with seven isolates of C. tropicalis from urine and blood cultures and from central venous catheter. C. tropicalis ATCC 750 was used as reference strain. Yeasts adhered (2 h) to epithelial cells and silicone and 24 h biofilm biomass were determined by crystal violet staining. Pseudohyphae formation ability was determined after growth in fetal bovine serum. Enzymes production (hemolysins, proteases, phospholipases) was assessed by halo formation on agar plates. Susceptibility to antifungal agents was determined by E-test. Regarding adhesion, it can be highlighted that C. tropicalis strains adhered significantly more to epithelium than to silicone. Furthermore, all C. tropicalis strains were able to form biofilms and to express total hemolytic activity. However, protease was only produced by two isolates from urine and by the isolates from catheter and blood. Moreover, only one C. tropicalis (from catheter) was phospholipase positive. All isolates were susceptible to voriconazole, fluconazole and amphotericin B. Four strains were susceptible-dose dependent to itraconazole and one clinical isolate was found to be resistant.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Blood; Candida tropicalis; Candidiasis; Catheterization; Cell Adhesion; Cells, Cultured; Enzymes; Epithelial Cells; Equipment and Supplies; Fluconazole; Fungal Proteins; Hemolysin Proteins; Humans; Microbial Sensitivity Tests; Pyrimidines; Triazoles; Urine; Virulence Factors; Voriconazole

Infections due to Candida spp. are frequent, particularly in immunocompromised and intensive care unit patients. Antifungal susceptibility tests are now required to optimize antifungal treatment given the emergence of acquired antifungal resistance in some Candida species. An antifungal susceptibility automated method, the Vitek 2 system (VK2), was evaluated. VK2 was compared to the CLSI broth microdilution reference method and the Etest procedure. For this purpose, 205 clinical isolates of Candida spp., including 11 different species, were tested for fluconazole, voriconazole, and amphotericin B susceptibility. For azoles, essential agreement ranged from 25% to 100%, depending on the method used and the Candida species tested. Categorical agreements for all of the species averaged 92.2% and ranged from 14.3 to 100%, depending on the 24-h or 48-h MIC reading by the Etest and CLSI methods and on the Candida species. Results obtained for Candida albicans showed excellent categorical and essential agreements with the two comparative methods. For Candida glabrata, the essential agreement was high with the CLSI method but low with the Etest method, and several very major errors in interpretation were observed between VK2 and the Etest method for both azoles. Low MICs of fluconazole were obtained for all of the Candida krusei isolates, but the VK2 expert software corrected all of the results obtained to resistant. Amphotericin B results showed MICs of < or = 1 mg/liter for 201 (VK2), 190 (CLSI), and 202 (Etest) isolates. The AST-YS01 Vitek 2 card system (bioMérieux) is a reliable and practical standardized automated antifungal susceptibility test. Nevertheless, more assays are needed to better evaluate C. glabrata fluconazole sensitivity.

Topics: Amphotericin B; Antifungal Agents; Automation; Candida; Candidiasis; Fluconazole; Humans; Intensive Care Units; Microbial Sensitivity Tests; Pyrimidines; Statistics as Topic; Triazoles; Voriconazole

The aim of the present study was to evaluate the in vitro activity and synergism of the combinations of amphotericin B/caspofungin and amphotericin B/posaconazole against Candida albicans, grown either as planktonic cells or in biofilms.. Ten C. albicans bloodstream isolates used in this study were collected from intensive care patients admitted to the Vienna University Hospital between 2006 and 2007. Chequerboard tests were employed to determine the efficacy of the antifungal combinations amphotericin B/caspofungin and amphotericin B/posaconazole against both planktonic cells and biofilms. C. albicans biofilms were prepared using the static microtitre plate model. The activity of antifungal combination therapy was determined by visual reading for planktonic cells and using the XTT assay for biofilms.. For Candida biofilms the median MIC was 4 mg/L for amphotericin B and caspofungin, and >256 mg/L for posaconazole. The combination amphotericin B/posaconazole yielded synergism [fractional inhibitory concentration index (FICI) <0.26], whereas amphotericin B/caspofungin yielded indifferent interaction only (FICI 0.75-1.25) against all isolates when grown in biofilms. Under planktonic conditions, synergism was demonstrable for the combination amphotericin B/caspofungin against 4 of the 10 isolates, whereas the combination of caspofungin/posaconazole was indifferent against all tested isolates.. We showed that MICs for planktonic and biofilm forms of C. albicans were much lower when treated with an antifungal combination than when treated with single agents. The combination of amphotericin B/posaconazole yielded synergism against Candida biofilms, whereas amphotericin B/caspofungin yielded indifferent interaction.

Topics: Amphotericin B; Antifungal Agents; Austria; Biofilms; Candida albicans; Candidiasis; Caspofungin; Drug Synergism; Echinocandins; Fungemia; Humans; Intensive Care Units; Lipopeptides; Microbial Sensitivity Tests; Triazoles

Candida parapsilosis is a very rare cause of meningitis. Though several cases have now been reported in neonates and children, only one has been described in an adult. We report on a 55-year-old male that was admitted due to altered mental status. He had recent sinus drainage and polypectomy, craniotomy with drainage of brain abscess, and ventriculo-peritoneal shunt placement. On admission, imaging studies showed no evidence of shunt dysfunction but did reveal extensive white matter decreased attenuation. Microscopic examination of the first 10 daily cerebrospinal fluid (CSF) cultures revealed yeast. Flucytosine and liposomal amphotericin B were started and externalization of shunt was performed on day 3. On day 8, CSF culture from admission grew C. parapsilosis; fluconazole was added. On day 10, daily CSF still showed yeast and cultures consistently grew C. parapsilosis. Shunt was removed and bilateral ventriculostomy drains were inserted. CSF after procedure as well as at follow-up examinations throughout his 3-month hospitalization were negative for yeast. Extended treatment with flucytosine and fluconazole was initiated. At 8-month follow-up, successful treatment of C. parapsilosis infection without recurrence was confirmed. This case underscores the need for suspicion of C. parapsilosis as a cause of meningitis after invasive surgeries in adults.

Topics: Amphotericin B; Antifungal Agents; Brain Abscess; Candida; Candidiasis; Drainage; Fluconazole; Flucytosine; Follow-Up Studies; Humans; Injections, Intravenous; Male; Meningitis, Bacterial; Middle Aged; Recurrence; Treatment Outcome; Ventriculoperitoneal Shunt

To report a case of Candida meningitis post Gliadel wafer (polifeprosan 20 with carmustine implant) placement successfully treated with the combination of intrathecal and intravenous amphotericin B.. A 33-year-old white female with a history of recurrent oligodendroglioma was admitted to the neuroscience intensive care unit with acute mental status changes. Computed tomography of the head demonstrated a cystic dilation of the right frontoparietal tumor resection cavity with Gliadel wafers in place and the presence of a large fluid collection. The cavity was debrided surgically and a ventriculostomy catheter was left in place. Cerebrospinal fluid (CSF) cultures were positive for Candida albicans and methicillin-resistant coagulase-negative Staphylococcus spp. Antiinfective therapy with intrathecal and intravenous amphotericin B as well as flucytosine and vancomycin was started. The patient had subsequent improvement in clinical manifestations, resolution of CSF leukocytosis, and mycologic cure.. Candida meningitis occurs primarily in the setting of immunosuppression, intravenous drug abuse and following neurosurgical procedures. Secondary bacterial and fungal infections have been reported following Gliadel wafer placement in patients with brain tumor resection. Candida meningitis has traditionally been treated with intravenous amphotericin B with or without oral flucytosine. There have been reports of treatment with intrathecal amphotericin B with variable clinical outcomes.. This case demonstrates successful treatment of Candida meningitis post Gliadel wafer placement with the combination of intrathecal and intravenous amphotericin B. This treatment modality may provide an effective therapeutic option for other patients with Candida meningitis, especially those unresponsive to intravenous therapy.

Topics: Amphotericin B; Antineoplastic Agents; Candidiasis; Carmustine; Decanoic Acids; Drug Implants; Female; Humans; Injections, Intravenous; Injections, Spinal; Meningitis, Fungal; Oligodendroglioma; Polyesters

The post-antifungal effect (PAFE) has been shown to affect Candida pathogenicity, but there is little information on either PAFE or its association with the colonization traits of Candida glabrata. The objective of this study was to determine, in vitro, the PAFE on 14 C. glabrata isolates following exposure to amphotericin B (AMB), nystatin (NYS), ketoconazole (KETO) and 5-fluorocytosine (5FC). In addition, we evaluated the impact of PAFE on yeast adherence to buccal epithelial cells (BEC), cell-surface-hydrophobicity (CSH) and biofilm growth (BG) on denture acrylic surfaces. PAFE was induced following a 1-h exposure of yeasts to (x1-x4MIC) of AMB, NYS, KETO and 5FC in RPMI medium and, measured using automated turbidometry. The BEC adhesion, CSH and BG assays were performed by the methods of Kimura & Pearsall, Sweet et al., and Jin et al., respectively. Significant differences in PAFE (P < 0.001) were observed after exposure to AMB and NYS, but not KETO and 5FC. Following exposure to AMB, NYS, KETO and 5FC, significant inter-strain differences (P < 0.001) were observed in percentage terms in adhesion (39.0%, 43.48%, 38.28%, 35.07%) and biofilm growth (42.86%, 39.86%, 42.81%, 36.38%), respectively. Short exposure of C. glabrata to sub-cidal concentrations of antifungals modulates yeast growth and also affects some of their colonization traits.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Biomass; Candida glabrata; Candidiasis; Cell Adhesion; Cell Wall; Epithelial Cells; Flucytosine; Humans; Hydrophobic and Hydrophilic Interactions; Ketoconazole; Nephelometry and Turbidimetry; Nystatin

Invasive fungal infections are serious complications of cancer therapy. We present a case report of a 12-year-old boy diagnosed with abdominal non-Hodgkin lymphoma and fecal and Candida peritonitis during induction chemotherapy. The invasive mycosis was managed using a combined approach of systemic antifungal agents including efungumab and surgical interventions. Efungumab, a recombinant antibody that inhibits extracellular heat shock protein 90, was used in combination with amphotericin B colloid dispersion after the failure of standard approaches.

Topics: Abdominal Neoplasms; Amphotericin B; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antifungal Agents; Candidiasis; Child; Drug Therapy, Combination; HSP90 Heat-Shock Proteins; Humans; Lymphoma, Non-Hodgkin; Male; Peritonitis

The goal of this study was to compare in vitro and in vivo efficacy of moxifloxacin and liposomal amphotericin B (Amp-B) monotherapies and combination treatment against Candida albicans in an exogenous endophthalmitis model in rabbit eyes. Microplate dilution tests and checkerboard analysis were performed to detect in vitro efficacies. Endophthalmitis was induced by intravitreal injection of C. albicans in 40 rabbit eyes with simultaneous intravitreal drug injection according to prophylactic treatment groups. Group 1 (control group) received 0.1 mL of balanced salt solution, group 2 (moxi group) 100 microg moxifloxacin/0.1 mL, group 3 (Amp-B group) 10 microg liposomal Amp-B/0.1 mL, and group 4 (combi group) both 100 microg moxifloxacin/0.1 mL [DOSAGE ERROR CORRECTED] and 10 microg liposomal Amp-B/0.05 mL intravitreally. Clinical examination, quantitative analysis of microorganisms, and histopathologic examination were performed as in vivo studies. The minimum inhibitory concentration of liposomal Amp-B against C. albicans was found to be 1 microg/mL. Moxifloxacin showed no inhibition of in vitro C. albicans growth. The minimum inhibitory concentration values of liposomal Amp-B for C. albicans were reduced two- to eightfold with increasing concentrations of moxifloxacin in vitro. In vivo, there was no C. albicans growth in the combi group (zero of eight eyes), whereas three eyes (37.5%) showed growth in the Amp-B group. Vitreous inflammation, retinal detachment, focal retinal necrosis, and outer nuclear layer loss were found to be lower in the moxi group compared with the control group. Ganglion cell and inner nuclear layer loss was observed in all eyes (100%) in both the moxi and combi groups, whereas only in 25% (two of eight eyes) in the Amp-B group. Moxifloxacin strongly augments the efficacy of liposomal Amp-B against C. albicans in vitro, although it has no in vitro antifungal activity when used alone. It is interesting that we found a synergistic effect for in vitro tests but failed to demonstrate it in vivo. When 100 microg moxifloxacin/0.1 mL is given intravitreally, it has some toxic effects that are limited to the inner retinal layers.

Topics: Amphotericin B; Animals; Antifungal Agents; Aza Compounds; Candida albicans; Candidiasis; Colony Count, Microbial; Disease Models, Animal; Drug Resistance, Fungal; Drug Therapy, Combination; Endophthalmitis; Eye Diseases; Eye Infections, Bacterial; Eye Infections, Fungal; Fluoroquinolones; Microbial Sensitivity Tests; Moxifloxacin; Quinolines; Rabbits; Vitreous Body

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; Fungemia; Humans; Male; Young Adult

To study the demographic changes of yeasts causing invasive infections in Taiwan, especially with respect to species distribution and antifungal susceptibility, we analyzed isolates obtained from four sterile sites of patients in 19 hospitals in 2002 (155 strains) and again from the same hospitals in 2006 (208 strains). Blood was the most common source of the yeasts, accounting for 73.8% of the total isolates, followed by ascites (21.5%), cerebrospinal fluid (3%), and synovia (1.7%). Candida albicans was the most frequently recovered species (50.1% of the total), followed by Candida tropicalis (20.7%), Candida glabrata (11.6%), Candida parapsilosis (8.5%), Cryptococcus neoformans (3.9%), Candida krusei (0.8%), and nine other species (4.3%). There were one (0.3%) and seven (1.9%) isolates with minimum inhibitory concentrations (MICs) of amphotericin B > or =2 mg/l after 24 h and 48 h incubation, respectively. In addition, there were 15 (4.3%) and 31 (8.6%) isolates with MICs of fluconazole > or =64 mg/l under the same conditions. The MIC(90) value of amphotericin B was 1 mg/l. The MIC(90) values of fluconazole were 4 mg/l after 24 h incubation and 32 mg/l after 48 h incubation. Interestingly, MICs for fluconazole > or =64 mg/l after 24 h were significantly higher for isolates obtained in 2006 than those in 2002 after 24 h (7.1% vs. 0.7%, p =0.009) and 48 h (13.5% vs. 2%, p =0.0003) incubations. The demographic difference between these two surveys is mainly due to one species, C. tropicalis.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Fluconazole; Humans; Microbial Sensitivity Tests; Population Surveillance; Taiwan

The yeast Candida albicans is an opportunistic human fungal pathogen and the cause of superficial and systemic infections in immunocompromised patients. The classes of antifungal agents most commonly used to treat Candida infections are the azoles, polyenes, and echinocandins. In the present study, we identified changes in C. albicans protein abundance using two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectroscopy following exposure to representatives of the azole (ketoconazole), polyene (amphotericin B), and echinocandin (caspofungin) antifungals in an effort to elucidate the adaptive responses to these classes of antifungal agents. We identified 39 proteins whose abundance changed in response to ketoconazole exposure. Some of these proteins are involved in ergosterol biosynthesis and are associated with azole resistance. Exposure to amphotericin B altered the abundance of 43 proteins, including those associated with oxidative stress and osmotic tolerance. We identified 50 proteins whose abundance changed after exposure to caspofungin, including enzymes involved in cell wall biosynthesis and integrity, as well as the regulator of beta-1,3-glucan synthase activity, Rho1p. Exposure to caspofungin also increased the abundance of the proteins involved in oxidative and osmotic stress. The common adaptive responses shared by all three antifungal agents included proteins involved in carbohydrate metabolism. Some of these antifungal-responsive proteins may represent potential targets for the development of novel therapeutics that could enhance the antifungal activities of these drugs.

Topics: Adaptation, Physiological; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Caspofungin; Drug Resistance, Fungal; Echinocandins; Electrophoresis, Gel, Two-Dimensional; Ergosterol; Humans; Ketoconazole; Lipopeptides; Oxidative Stress; Proteome; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Water-Electrolyte Balance

This is a retrospective observational study of clinical and epidemiologic data from bloodstream yeast infections over 5 years (2004-2008) in a tertiary-care hospital. During this period, there were 52 such infections, at a rate of 2.4 per 1,000 hospital admissions. Non-C. albicans Candida species and other genera were responsible for 82% of infections, with C. tropicalis and C. parapsilosis being the most common. In 2008 no C. albicans infections occurred. Several uncommon fungal pathogens were observed, including Trichosporon asahii, Rhodotorula spp. and Candida zeylanoides. Of 16 isolates tested, 3 (19%) were resistant to fluconazole, including one C. zeylanoides (MIC 8 microg/ml) and one C. tropicalis (MIC 16 microg/ml) isolate, as well as intrinsically resistant C. krusei. All isolates tested were susceptible to itraconazole (n = 7) and amphotericin B (n = 8). Yeast infections were associated with severe underlying diseases, mainly hematological/solid cancers (71%), hospitalization in the ICU (41%), central venous catheters (80%), and use of antimicrobials (94%). The overall mortality rate was 50%. Our finding of a predominance of non-C. albicans Candida species infection with uncommon yeasts, and fluconazole resistance, suggests the need for continuous surveillance of fungemia and of antibiotic susceptibility trends, in order to adopt treatment strategies applicable to particular healthcare institutions.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Child; Child, Preschool; Female; Fungemia; Hospitals; Humans; Infant; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Rhodotorula; Trichosporon; Young Adult

Intracranial fungal masses are uncommon diseases, but their incidence is increasing, most often due to the prolonged survival of patients with different immunodeficiencies. The management of patients with intracranial fungal masses included stereotactic biopsy for diagnosis, partial or radical surgery excision and prolonged antifungal therapy.. We report the case of a 51-year-old diabetic man with a history of psoas abscess due to Candida albicans 1 year before the onset of neurological symptoms, including headache and generalized tonoclonic seizures.. Magnetic resonance imaging showed a single lesion located in the right parietal lobe with mass effect, surrounding edema and enhancement after injection of gadolinium. The material was purulent.. Direct microscopic examination showed hyaline, branched and septate hyphae compatible with fungal elements.. Fungal infections, especially due to Candida species, should be considered in diabetic patients with parenchymal brain abscesses. Radical excision followed by prolonged antifungal therapy based on fluconazole or amphotericin B is necessary to improve the prognosis of this type of patients.

Topics: Amphotericin B; Antifungal Agents; Brain Abscess; Candida albicans; Candidiasis; Combined Modality Therapy; Craniotomy; Deoxycholic Acid; Diabetes Mellitus, Type 2; Drug Combinations; Drug Therapy, Combination; Fluconazole; Humans; Hyphae; Magnetic Resonance Imaging; Male; Mannitol; Middle Aged; Parietal Lobe; Psoas Abscess

Topics: Amphotericin B; Candidiasis; Emphysema; Female; Humans; Middle Aged; Pyelonephritis; Radiography; Renal Dialysis

Contradictory results such as synergy or indifferent effect, have been reported about the interactions between quinolones and antifungal drugs in different studies. The aim of this study was to investigate the in vitro susceptibilities of Candida spp. to moxifloxacin (MOX) alone and MOX + amphotericin B (AmB) combination. A total of 20 strains were included to the study, of which 19 were clinical isolates (10 Candida albicans, 4 Candida glabrata, 2 Candida parapsilosis, 1 Candida tropicalis, 1 Candida pelliculosa ve 1 Candida sake) and 1 was a standard strain (C. albicans ATCC 90028). In vitro susceptibilities of the strains to MOX with AmB were investigated by broth microdilution method according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI), and in vitro interaction of these drugs were determined by a chequerboard titration method. Minimal inhibitory concentration (MIC) values of Candida spp. for MOX were found > or = 400 microg/ml indicating that MOX, by itself has no antifungal activity. AmB MIC values were found 1 microg/ml in 11 of the clinical isolates, and < or = 0.5 microg/ml in the other 8 clinical isolates and 1 standard strain. The inhibitor activity of AmB was slightly enhanced when combined with MOX, there being a decrease of 1-4 fold dilutions in the AmB MICs against all isolates tested. Synergistic effect between MOX and AmB, defined as a fractional inhibitory concentration (FIC) index as < or = 0.5, was observed in 90% (18/20; all were clinical isolates) of the strains, whereas indifferent effect (FIC = 1) was detected in 10% (2/20; 1 was clinical and 1 was standard strain) of the strains. Antagonistic effect was not observed for this combination even at 48th hours. It was concluded that these preliminary results should be confirmed by large-scaled in vitro and in vivo studies to evaluate MOX + AmB combination as a therapeutic option for the treatment of Candida infections.

Topics: Amphotericin B; Anti-Infective Agents; Antifungal Agents; Aza Compounds; Candida; Candidiasis; Drug Synergism; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Moxifloxacin; Quinolines

Over the past years, the incidence of yeast infections, especially candidiasis, has increased. It is known that birds, including cockatiels, harbor potentially pathogenic yeasts to human beings in their gastrointestinal tract. Thus, this work aims at determining the in vitro antifungal susceptibility and phospholipase activity of Candida spp. isolated from the gastrointestinal tract and stools of cockatiels. Sixty cockatiels were assessed and samples were collected from oral cavity, crop and cloaca and stools were collected from cages where birds were kept. Yeast species were identified according to morphological and biochemical characteristics. Amphotericin B, itraconazole and fluconazole were tested against 39 C. albicans; 12 C. tropicalis; 7 C. parapsilosis and 1 C. krusei, through broth microdilution test. These same isolates were also tested for phospholipase production, on egg yolk agar. For amphotericin B, itraconazole and fluconazole, MICs were 0.25-1 μg/mL, 0.03125 to ≥16 μg/mL and 0.5 to ≥64 μg/mL, respectively, and resistance to itraconazole and fluconazole was observed in 14 (35.89%) and 4 (10.26%) C. albicans isolates, respectively. All C. albicans were positive for phospholipase production, out of which 74.36% presented high enzymatic activity. Among non-albicans Candida species, 40% produced phospholipase. The results show that cockatiels might represent a hazard to human health, as sources of infections caused by resistant Candida spp., especially to immunocompromised individuals, children and elderly.

Topics: Amphotericin B; Animals; Antifungal Agents; Bird Diseases; Brazil; Candida; Candidiasis; Cockatoos; Feces; Fluconazole; Gastrointestinal Diseases; Itraconazole; Microbial Sensitivity Tests; Phospholipases; Statistics, Nonparametric; Zoonoses

Candida glabrata endophthalmitis following keratoplasty is rare and almost always associated with positive donor rim culture.. A 63-year-old patient, diagnosed Fuch's endothelial dystrophy in both eyes underwent a penetrating keratoplasty in his right eye. He had multiple underlying medical problems, which included diabetes mellitus, hypertension, hypoadrenalism on oral dexamethasone and fatty liver secondary to hypertrigliseridemia. He developed multiple suture abscesses, corneal haziness, retrocorneal white plaques and a level of hypopyon two weeks after an uneventful penetrating keratoplasty in his right eye. Cultures of the donor button and the transport media culture were negative. Candida glabrata was isolated successfully from the aqueous and vitreous taps. He was treated with a combination of topical, intracameral, intravitreal and intravenous Amphotericin B. His final visual acuity remained poor due to the haziness of the corneal button.. Candida glabrata endophthalmitis following penetrating keratoplasty can occur in negative donor rim and transport media cultures. The growth of the organism is facilitated by the patient's immunocompromised status. Awareness by the ophthalmologists and appropriate choice of antibiotics are mandatory in this challenging condition.

Topics: Abscess; Administration, Topical; Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Drug Administration Schedule; Endophthalmitis; Eye Diseases; Fuchs' Endothelial Dystrophy; Humans; Injections, Intraocular; Injections, Intravenous; Keratoplasty, Penetrating; Male; Middle Aged; Sutures; Transplants; Ultrasonography; Vitreous Body

We report a series of 4 patients who experienced a low-grade mycotic endophthalmitis 3 to 7 months after uneventful cataract surgery. In all patients, the capsular bag was irrigated several times and amphotericin B was instilled intraocularly as well as systemically. In the fourth patient, a pars plans vitrectomy was been performed. Microbiological examination of aqueous humor samples revealed Candida parapsilosis in 3 patients and Candida albicans in 1 patient as causative microorganisms. At follow-up examinations performed up to 12 months after the lavage, visual acuities were 0.2, 0.1, 0.1, and hand motion in the 4 patients, respectively. The main reason for the remaining reduction in visual acuity was retinal and optic nerve atrophy. The findings show that a mycotic etiology of postoperative low-grade infectious endophthalmitis should be considered.. No author has a financial or proprietary interest in any material or method mentioned.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Cataract Extraction; Combined Modality Therapy; Endophthalmitis; Eye Infections, Fungal; Humans; Middle Aged; Postoperative Complications; Visual Acuity; Vitrectomy; Vitreous Body

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Corneal Ulcer; Dacryocystitis; Dexamethasone; Drug Therapy, Combination; Echinocandins; Eye Infections, Fungal; Female; Humans; Keratoplasty, Penetrating; Lacrimal Apparatus; Lipopeptides; Recurrence; Reoperation

Among nosocomial infections in the newborns, the incidence of fungal infections has been rising over the last decades. Fluconazole has been a new option for treatment however, expanded use of the drug brought up the development of resistance. In this study, species of the Candida isolates from neonates with candida infections, their antifungal susceptibilities and the effectiveness of the therapy were evaluated. All the species of Candida isolates from blood, urine and sterile body fluids of 54 neonates and their antifungal susceptibilities were evaluated retrospectively over the 13-year period. Demographic characteristics, risk factors, infection foci, Candida species causing infection and their in vitro susceptibilities for fluconazole (FCZ) and amphotericin B (AMB) and treatment responses were analyzed. The antifungal susceptibility testing of isolates was performed by microdilution technique. The median birth weight and gestational age of the study groups were 1735 (660-3990) g and 33 (24-40) weeks, respectively. Among the patients, 19 (35%) were term, while 35 (65%) were preterm [< 32 weeks n = 20 (37%), < 28 weeks n = 7 (13%)]. The percentage of low birth weight infants was 65% (42% was < 1500 g, 13% was < 1000 g). Candida spp. were isolated mostly from blood samples (63%), followed by urine (46%), cerebrospinal fluid (CSF; 5%), peritoneal fluid (3%) and endotracheal aspirate (2%). Multifocal growth was determined in 10 (18%) cases. The isolated species were C.albicans (n =36) as being the most common isolate followed by C.parapsilosis (n = 12), C.tropicalis (n = 1), C.kefyr (n = 1), C.lusitaniae (n = 1), C.pelluculosa (n = 1) and Candida spp. (n = 2). Prior antibiotic use, long term hospitalization, total parenteral nutrition and use of lipid solutions, prematurity and catheter use were determined as the most frequently associated factors causing candidal infections. A congenital abnormality, mainly myeloschisis and hydrocephaly, was detected in 18 (33%) of the cases. Overall FCZ resistance rate was 5.5% and the rate of resistance according to the species was 2.8% for C.albicans and 11% for non-albicans isolates. No resistance was observed to AMB. Initial treatment was FCZ for 78% and AMB for 22% of the newborns. The treatment was switched to AMB in 15 (28%) cases because of no clinical or laboratory response to FCZ although only three of these babies showed resistance to FCZ (MIC ≥ 64 mcg/ml). Among the cases with no clinical/microbiological respo

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; Drug Resistance, Fungal; Fluconazole; Gestational Age; Humans; Incidence; Infant, Newborn; Microbial Sensitivity Tests; Retrospective Studies; Turkey

Candidaemia associated with intravascular catheter-associated infections is of great concern due to the resulting high morbidity and mortality. The antibiotic lock technique (ALT) was previously introduced to treat catheter-associated bacterial infections without removal of catheter. So far, the efficacy of ALT against Candida infections has not been rigorously evaluated. We investigated in vitro activity of ALT against Candida biofilms formed by C. albicans, C. glabrata, and C. tropicalis using five antifungal agents (caspofungin, amphotericin B, itraconazole, fluconazole, and voriconazole). The effectiveness of antifungal treatment was assayed by monitoring viable cell counts after exposure to 1 mg/mL solutions of each antibiotic. Fluconazole, itraconazole, and voriconazole eliminated detectable viability in the biofilms of all Candida species within 7, 10, and 14 days, respectively, while caspofungin and amphotericin B did not completely kill fungi in C. albicans and C. glabrata biofilms within 14 days. For C. tropicalis biofilm, caspofungin lock achieved eradication more rapidly than amphotericin B and three azoles. Our study suggests that azoles may be useful ALT agents in the treatment of catheter-related candidemia.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida albicans; Candida glabrata; Candida tropicalis; Candidiasis; Caspofungin; Catheter-Related Infections; Catheterization, Central Venous; Drug Administration Routes; Echinocandins; Fluconazole; Humans; Itraconazole; Lipopeptides; Microbial Sensitivity Tests; Pyrimidines; Triazoles; Voriconazole

The occurrence of Candida spp. was investigated during a three-year period in two neonatal intensive care units, Budapest, Hungary. The species distribution among the 41 analysed cases was the following: C. albicans (30/41, 73%), C. parapsilosis (10/41, 24%) and C. glabrata (1/41, 3%). All of the isolates were susceptible to the tested drugs. There was a significant difference in the birth weight, the gestational age <30 weeks and the occurrence of caesarean section between the C. albicans and the C. parapsilosis groups of the cases. Respiratory tract colonization was the same (76-77%) in the extremely low birth weight (ELBW) and the very low birth weight (VLBW) groups. Comparing the ELBW, VLBW, and >1500 g birth weight groups, significant difference was found in the parenteral nutrition, the gestation weeks <36 or <30, the polymicrobial infection and the transfusion. The ratio of C. albicans, C. parapsilosis and C. glabrata was 9:7:1 in ELBW group; 6:3:0 in VLBW group and 15:1:0 in >1500 g group. The mortality rate for C. parapsilosis was higher than for C. albicans.

Topics: Amphotericin B; Candida; Candida albicans; Candida glabrata; Candidiasis; Cesarean Section; Female; Fluconazole; Gestational Age; Humans; Hungary; Infant, Extremely Low Birth Weight; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Intensive Care Units, Neonatal; Male; Parenteral Nutrition

Most Candida krusei strains are innately resistant to fluconazole (FLC) and can cause breakthrough candidemia in immunocompromised individuals receiving long-term prophylactic FLC treatment. Although the azole drug target, Erg11p, of C. krusei has a relatively low affinity for FLC, drug efflux pumps are also believed to be involved in its innate FLC resistance. We describe here the isolation and characterization of Abc1p, a constitutively expressed multidrug efflux pump, and investigate ERG11 and ABC1 expression in C. krusei. Examination of the ERG11 promoter revealed a conserved azole responsive element that has been shown to be necessary for the transcription factor Upc2p mediated upregulation by azoles in related yeast. Extensive cloning and sequencing identified three distinct ERG11 alleles in one of two C. krusei strains. Functional overexpression of ERG11 and ABC1 in Saccharomyces cerevisiae conferred high levels of resistance to azoles and a range of unrelated Abc1p pump substrates, while small molecule inhibitors of Abc1p chemosensitized C. krusei to azole antifungals. Our data show that despite the presence of multiple alleles of ERG11 in some, likely aneuploid, C. krusei strains, it is mainly the low affinity of Erg11p for FLC, together with the constitutive but low level of expression of the multidrug efflux pump Abc1p, that are responsible for the innate FLC resistance of C. krusei.

Topics: Amino Acid Sequence; Animals; Antifungal Agents; ATP-Binding Cassette Transporters; Azoles; Blotting, Northern; Blotting, Southern; Candida; Candidiasis; Cell Membrane; Chromosomes, Fungal; Drug Resistance, Fungal; Endoplasmic Reticulum; Humans; Phenotype; Plasmids; Reverse Transcriptase Polymerase Chain Reaction; Saccharomyces cerevisiae

Caspofungin is used for the treatment of acute invasive candidiasis and as salvage treatment for invasive aspergillosis. We report characteristics of isolates of Candida albicans and Aspergillus fumigatus detected in a patient with breakthrough infection complicating severe gastrointestinal surgery and evaluate the capability of susceptibility methods to identify candin resistance. The susceptibility of C. albicans to caspofungin and anidulafungin was investigated by Etest, microdilution (European Committee on Antibiotic Susceptibility Testing [EUCAST] and CLSI), disk diffusion, agar dilution, and FKS1 sequencing and in a mouse model. Tissue was examined by immunohistochemistry, PCR, and sequencing for the presence of A. fumigatus and resistance mutations. The MICs for the C. albicans isolate were as follows: >32 microg/ml caspofungin and 0.5 microg/ml anidulafungin by Etest, 2 microg/ml caspofungin and 0.125 microg/ml anidulafungin by EUCAST methods, and 1 microg/ml caspofungin and 0.5 microg/ml anidulafungin by CLSI methods. Sequencing of the FKS1 gene revealed a mutation leading to an S645P substitution. Caspofungin and anidulafungin failed to reduce kidney CFU counts in animals inoculated with this isolate (P > 0.05 compared to untreated control animals), while both candins completely sterilized the kidneys in animals infected with a control isolate. Disk diffusion and agar dilution methods clearly separated the two isolates. Immunohistochemistry and sequencing confirmed the presence of A. fumigatus without FSK1 resistance mutations in liver and lung tissues. Breakthrough disseminated aspergillosis and candidiasis developed despite an absence of characteristic FKS1 resistance mutations in the Aspergillus isolates. EUCAST and CLSI methodology did not separate the candin-resistant clinical isolate from the sensitive control isolate as well as did the Etest and agar methods.

Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Candida albicans; Candidiasis; Caspofungin; Colony Count, Microbial; Echinocandins; Humans; Immunohistochemistry; Injections, Intraperitoneal; Lipopeptides; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Polymerase Chain Reaction

Fluconazole based novel mimics containing 1,2,3-triazole were designed and synthesized as antifungal agents. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 12, 15, and 16 were found to be more potent against Candida fungal pathogens than control drugs fluconazole and amphotericin B. The studies presented here provide structural modification of fluconazole to give 1,2,3-trazole containing molecules. Furthermore, these molecules were evaluated in vivo against Candida albicans intravenous challenge in Swiss mice and antiproliferative activities were tested against human hepatocellular carcinoma Hep3B and human epithelial carcinoma A431. It was found that compound 12 resulted in 97.4% reduction in fungal load in mice and did not show any profound proliferative effect at lower dose (0.001 mg/ml).

Topics: Animals; Antifungal Agents; Bile Acids and Salts; Candida albicans; Candidiasis; Cell Line, Tumor; Chemistry, Pharmaceutical; Drug Design; Drug Screening Assays, Antitumor; Fluconazole; Humans; Inhibitory Concentration 50; Mice; Models, Chemical; Triazoles

This study retrospectively reviews the susceptibility of 135 baseline ICU candidemia isolates (from 1997 to 2007) to nine antifungals as determined by the AFST-EUCAST microdilution method and identifies the most frequent causative agents of confirmed point-source candidemia outbreaks in local intensive care units. A minority of common and rare Candida species displayed decreased susceptibility to all antifungals.

Topics: Antifungal Agents; Candida; Candidiasis; Data Collection; Disease Susceptibility; Greece; Humans; Intensive Care Units; Microbial Sensitivity Tests; Retrospective Studies

Experience with anidulafungin against Candida krusei is limited. Immunosuppressed mice were injected with 1.3 x 10(7) to 1.5 x 10(7) CFU of C. krusei. Animals were treated with saline, 40 mg/kg fluconazole, 1 mg/kg amphotericin B, or 10 and 20 mg/kg anidulafungin for 5 days. Anidulafungin improved survival and significantly reduced the number of CFU/g in kidneys and serum beta-glucan levels.

Topics: Anidulafungin; Animals; Antifungal Agents; beta-Glucans; Candida; Candidiasis; Disease Models, Animal; Echinocandins; Kidney; Male; Mice

We evaluated the efficacies of posaconazole and voriconazole in comparison with that of amphotericin B in a systemic murine infection by Candida krusei. Posaconazole at 50 mg/kg/day and voriconazole at 40 and 60 mg/kg/day prolonged survival and reduced the fungal tissue burden in the kidneys of mice similarly to amphotericin B at 1.5 mg/kg/day and liposomal amphotericin B at 10 mg/kg/day. None of the treatments tested completely resolved the infection.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candidiasis; Kidney; Male; Mice; Pyrimidines; Random Allocation; Triazoles; Voriconazole

The aim of this study was to determine in vitro susceptibility profiles of Venezuelan strains of Candida spp. to four antifungal agents. One hundred and forty five (145) isolates were recovered during a 1-year period (June 2006 to June 2007) from clinical specimens of patients with severe Candida spp. infections in 15 hospitals. In vitro susceptibilities to amphotericin B, fluconazole, itraconazole and voriconazole were determined by modified Etest. Non Candida albicans Candida spp. were the most frequently isolated yeasts (72.4%) in comparison with C. albicans (27.6%). Candida spp. strains showed MIC ranges between <0.002 and 0.5 mug/ml to amphotericin B. While none were found to be resistant to voriconazole, 5.5% and 27.6% of the test strains were resistant to fluconazole and itraconazole, respectively. C. albicans remains the most susceptible of the yeasts studied to fluconazole and itraconazole (P<0.05) when compared with non C. albicans Candida spp. C. krusei showed the greater cross-resistance to azoles, followed by C. glabrata, C. tropicalis and C. parapsilosis, while C. albicans isolates did not demonstrate this characteristic. It is very important to carry out the correct species identification of clinical yeast isolates because they show up variations in both distribution and susceptibility profiles according to the hospital, patient's underlying disease, clinical specimen analyzed, and the geographical region in which the studies were conducted. The Mycology Department of the INHRR is the national reference center responsible for antifungal resistance surveillance, performing the susceptibility tests with isolates recovered from hospitalized patients in public health centres which do not have mycological diagnosis laboratories.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Azoles; Candida; Candida albicans; Candidiasis; Child; Child, Preschool; Drug Resistance, Fungal; Female; Fluconazole; Humans; Infant; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Population Surveillance; Pyrimidines; Triazoles; Venezuela; Voriconazole; Young Adult

There have been very few multicenter studies of the relationship between the use of antifungals and resistance to them. We investigated the antifungal susceptibility of 1,301 clinical isolates of Candida collected from nine Korean hospitals during a 3-month period in 2006 to explore the existence of this type of relationship. Antifungal usage in the preceding year, defined as the daily dose per 1,000 patient days (DDD/1,000 PD), was calculated for each hospital. Resistance to fluconazole, itraconazole, and amphotericin B was detected in 2, 9, and 0.2% of the isolates, respectively. The MIC(50)/MIC(90) values were 0.03/0.125 mg/L for voriconazole, 0.06/0.25 mg/l for caspofungin, and 0.03/0.125 mg/l for micafungin. The total usage of systemic antifungals varied considerably among the nine hospitals, ranging from 6.1 to 96.2 DDD/1,000 PD. No relationship was found between the use of fluconazole (MIC> or =64 mg/l) or itraconazole (MIC> or =1 mg/l) and resistance in the Candida species (P>0.05). However, significant correlations were found between the percentage of Candida isolates that were non-susceptible to fluconazole (MIC> or =16 mg/l) and fluconazole usage (r=0.733, P=0.025) or total antifungal usage (r=0.767, P=0.016).

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Drug Utilization; Fluconazole; Hospitals; Humans; Itraconazole; Korea; Microbial Sensitivity Tests

In this study, the susceptibility to amphotericin B of Candida spp. isolates obtained from patients with candidemia was related to their respective clinical outcomes. The susceptibility tests were carried out in three culture media: RPMI 1640, Antibiotic medium 3 and Yeast Nitrogen Base dextrose. We have found that minimal inhibitory concentrations and minimal fungicidal concentrations obtained using AM3 and YNBd media were significantly higher for Candida spp. from patients who died than for those from patients who survived the candidemia (P < 0.05). The assays with RPMI 1640 medium did not show these differences.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Culture Media; Drug Resistance, Fungal; Humans; Microbial Sensitivity Tests; Treatment Outcome

The in vitro activities of caspofungin plus amphotericin B against 50 Candida glabrata isolates were evaluated by the time-kill, disk diffusion, and Etest methods. In vitro experiments showed a positive interaction. Even though each of these methods uses different conditions and endpoints, the results of the different methods frequently agreed.

Topics: Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Drug Combinations; Drug Synergism; Echinocandins; Endpoint Determination; Humans; Lipopeptides; Microbial Sensitivity Tests; Time Factors

Amphotericin B (AmphoB) remains the preferred therapy for invasive fungal infections despite many side effects, such as nephrotoxicity and electrolyte imbalance. Our previous study suggested that high sodium (Na) intake >4 mEq/kg per day may be associated with lower nephrotoxicity in extremely premature infants treated with AmphoB. Subsequently, it became a standard of care in our unit to administer Na >4 mEq/kg per day to extremely premature infants treated with AmphoB. The purpose of this study was to evaluate the effect of high Na intake > 4 mEq/kg per day on the incidence of AmphoB-induced nephrotoxicity among extremely premature infants with birth weight <1250 gm. All extremely premature infants with birth weight <1250 gm born between 1992 and 2004 and treated with AmphoB for systemic fungal infections were included in the study. The study infants were divided into two groups: a control (CL) group (1/1992-12/1999, n = 21) consisting of extremely premature infants given a maintenance Na intake during AmphoB therapy, and a high sodium intake (High Na) group (1/2000-12/2004, n = 16) consisting of extremely premature infants given a high Na intake >4 mEq/kg per day during AmphoB therapy. Nephrotoxicity was defined as serum creatinine levels >1 mg/dl, urinary output (UOP) < 1 ml/kg per hour or a decrease in UOP of 50%, compared with the previous 2 days, and persisting for at least 2 days. Invasive fungal infection was diagnosed in 5.7% of the infants (44/763 infants). Thirty-seven infants were eligible for the study and seven were excluded. There were no differences between the two groups in gestational age, birth weight, age at fungal infection diagnosis, length of AmphoB therapy, daily fluid intake or hyponatremia. Nephrotoxicity was significantly higher in the CL group than in the High Na group (13/21 vs. 3/16; P = 0.02). In the CL group, nephrotoxicity occurred at (mean +/- SD) 1.9 +/- 3.2 days after the initiation of AmphoB treatment and lasted for 5.5 +/- 4.7 days. In this group, nephrotoxicity occurred in two of the 13 infants before the initiation of AmphoB therapy. In the High Na group, nephrotoxicity occurred before the start of AmphoB therapy in two of the three infants. In the third infant, nephrotoxicity lasted for 1 day. Mean Na intake was not different between the two groups during the 4-day period prior to AmphoB therapy. Mean Na intake during the first 10-day period of AmphoB therapy was significantly lower in the CL group (3.7 vs 6.2; P. High Na intake was associated with a reduction in the incidence of AmphoB-induced nephrotoxicity in extremely premature infants with birth weight <1250 gm. We recommend the use of a high Na intake of >4 mEq/kg per day for extremely premature infants during Amphotericin B therapy.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cohort Studies; Female; Humans; Infant, Newborn; Infant, Premature; Kidney; Male; Potassium, Dietary; Retrospective Studies; Sodium, Dietary

Amphotericin B (AmB) is the gold standard of antifungal treatment for the most severe invasive mycoses. In addition to the interaction of AmB with ergosterol in the fungi cell membrane, several studies have demonstrated oxidative damage involved in the fungicidal activity of AmB. In this study, allicin, an allyl sulphur compound from garlic, was shown to enhance significantly the effect of AmB against Candida albicans in vitro and in vivo, although allicin did not exert a fungicidal effect. Further study first demonstrated that allicin-mediated oxidative damage, such as phospholipid peroxidation in the plasma membrane, via influencing the defence of C. albicans against oxidative damage may be the cause of the synergistic interaction between allicin and AmB. We envision that a combination of AmB with allicin may prove to be a promising strategy for the therapy of disseminated candidiasis.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Colony Count, Microbial; Disulfides; Drug Synergism; Female; Mice; Mice, Inbred BALB C; Microbial Viability; Sulfinic Acids

Systemic candidiasis is a significant cause of morbidity and mortality in patients with hematologic disorders. The aim of this study was to determine the prevalence of systemic candidiasis and the efficiency of the polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELIZA) method for the early detection of Candida spp. in patients with hematologic malignancies. From 2004 to 2006, 194 patients with hematologic malignancies were evaluated for systemic candidiasis. Collected blood samples were assayed using the PCR-ELISA method for the presence of the bands on ethidium bromide stained gel, and for hybridization with Candida spp. as well. The female-to-male ratio was 61:133, the mean age was 33.7 years, and the mean hospitalization period was 21.2 days. Twenty-five patients (12.9%) had positive PCR-ELISA results for systemic candidiasis. The etiologic agents were Candida albicans (21 cases), C. tropicalis (3 cases), and C. krusei (1 case). The mean interval of PCR-ELISA positivity in blood samples before the manifestation of clinical signs was 12.6 days. Fungal PCR-ELISA assay became negative after 14 days when patients were treated successfully with amphotericin B, and the assay remained positive until death when the treatment failed. The PCR-ELISA method can potentially serve as a useful tool for the management of patients suffering from hematologic malignancies and at risk for systemic candidiasis.

Topics: Adolescent; Adult; Amphotericin B; Antibodies, Fungal; Antifungal Agents; Antigens, Fungal; Candida; Candidiasis; DNA, Fungal; Enzyme-Linked Immunosorbent Assay; Female; Hematologic Neoplasms; Humans; Length of Stay; Male; Middle Aged; Polymerase Chain Reaction; Prevalence; Time Factors

Although there are numerous reports of septic pyogenic arthritis after arthroscopic anterior cruciate ligament (ACL) reconstruction, there is limited information regarding the outcomes of fungal infection. We determined the outcomes of six patients with mycotic infection after regular ACL reconstruction. There were four males and two females with a mean age of 33 years. We determined the number of procedures performed, bone loss originating to control infection, and final reconstruction in these patients. An average of five arthroscopic lavage procedures had been performed at the referring centers. Fungal infection was diagnosed based on pathologic samples; five infections were the result of mucormycosis and one was Candida. After final débridement, the mean segmental bone loss was 12.8 cm. All patients were treated with intravenous antifungal coverage and cement spacers before final reconstruction. At final followup, all patients were free of clinical infection. Three had reconstruction with an allograft-prosthesis composite, two with hemicylindrical allografts, and one with an intercalary allograft arthrodesis. Despite the extremely unusual presentation of this complication, surgeons should be aware of potential and catastrophic consequences of this severe complication after ACL reconstruction.

Topics: Adult; Amphotericin B; Anterior Cruciate Ligament; Antifungal Agents; Candidiasis; Debridement; Female; Humans; Liposomes; Male; Middle Aged; Mucormycosis; Osteolysis, Essential; Plastic Surgery Procedures; Postoperative Complications; Retrospective Studies; Treatment Outcome

To develop an oral formulation of Amphotericin B (AmpB) with: (A) medium chain triglycerides, fatty acids and nonionic surfactants as a self-emulsifying drug delivery system (SEDDS); or (B) glyceryl mono-oleate (Peceol) with poly(ethylene glycol) (PEG)-phospholipids.. SEDDS formulations were prepared by simple mixing at 40 degrees C. Peceol/DSPE-PEG-lipid formulations were prepared by solvent evaporation. Parameters evaluated included: miscibility, solubility and emulsion droplet size after incubation in simulated gastric fluid (SGF) or simulated intestinal fluid (SIF) via dynamic light scattering. The stability of AmpB in Peceol/DSPE-PEG was evaluated in SGF and SIF. Phase stability of AmpB in Peceol+/-DSPE-PEG following thermal cycling was evaluated by atomic force microscopy (AFM). Aspergillus fumigatus (2.9-3.45 x 10(7) colony forming units per mL [CFU]) or Candida albicans (3-3.65 x 10(6) CFU per mL) were injected via the jugular vein; 48 h later male albino Sprague-Dawley rats (350-400 g) were administered either a single oral gavage of a Peceol-DSPE/PEG2000-based AmpB (10 mg AmpB/kg and 5 mg AmpB/kg for the Candida albicans study only) twice daily for 2 consecutive days, a single intravenous (i.v.) dose of Abelcet (5mg AmpB/kg), or physiologic saline (non-treated controls; n=9) once daily for 2 consecutive days. Antifungal activity was assessed by organ CFU concentrations and plasma galactomannan levels in the case of A. fumigatus and organ CFU concentrations in the case of Candida albicans. Plasma samples were taken from each animal prior to infection, 48 h after initiation of infection but prior to drug treatment and at the end of the study for plasma creatinine determinations as a measure of renal toxicity.. Mean diameter of SEDDS after 30 min in 150 mM NaCl at 37 degrees C was 200-400 nm. However, the Peceol/DSPE-PEG, where PEG MW was 350, 550, 750 or 2000, showed a greater solubilization of AmpB (5 mg/mL) compared to SEDDS formulations (100-500 microg/mL). Upon dispersion in SIF, Peceol/DSPE-PEG formulations generated submicron emulsion particle sizes varying slightly with PEG MW. Stability of the AmpB in Peceol/DSPE-PEG formulations in SGF or SIF was >80% after 2 h, and best for formulations containing DSPE-PEG 750 or 2000 compared to 350, 550 or Peceol only. Monoglyceride-Peceol-DSPE/PEG2000-based oral AmpB treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by >80% compared to non-treated controls without significant changes in plasma creatinine levels in the A. fumigatus infected rats. In addition, this formulation significantly decreased kidney fungal CFU concentrations by >75% at the 5 mg/kg dose and by >95% at the 10 mg/kg dose compared to non-treated controls without significant changes in the plasma creatinine levels in the Candida albicans-infected rats.. Novel lipid-based AmpB oral formulations were prepared that provide excellent drug solubilization, drug stability in simulated gastric and intestinal fluids and antifungal activity without renal toxicity in rats infected with A. fumigatus and C. albicans.

Topics: Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Candida albicans; Candidiasis; Chemistry, Pharmaceutical; Drug Stability; Humans; Male; Rats; Rats, Sprague-Dawley; Solubility

Micafungin (MCFG) is an echinocandin antifungal agent that exhibits potent activity against most species of Candida and Aspergillus. We investigated the in vitro antifungal combination effects of MCFG with four other antifungal agents - fluconazole (FLCZ), voriconazole (VRCZ), amphotericin B, and flucytosine - against clinical isolates of 54 Candida spp. by checkerboard analysis. The synergistic antifungal effects of MCFG-FLCZ and MCFG-VRCZ were 11% and 15%, respectively, and the latter displayed a synergistic activity of 63% against Candida glabrata. Antagonism was not observed in any of the combinations tested.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Synergism; Echinocandins; Fluconazole; Flucytosine; Humans; Lipopeptides; Micafungin; Pyrimidines; Triazoles; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Echinocandins; Fungemia; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Lipopeptides; Male

Micafungin is an echinocandin-class antifungal agent licensed for treatment of invasive disease in adults. The optimal dosing regimens have not been established for infants. We describe a premature infant who developed hepatitis and cholestasis during micafungin therapy initiated for protracted candidemia. Practitioners should be aware of this potential adverse effect if using micafungin in young patients.

Topics: AIDS-Related Opportunistic Infections; Alanine Transaminase; Amphotericin B; Antifungal Agents; Aspartate Aminotransferases; Candidiasis; Chemical and Drug Induced Liver Injury; Cholestasis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Echinocandins; Female; Fungemia; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Lipopeptides; Liver Function Tests; Micafungin

Topics: Amphotericin B; Antifungal Agents; Brain; Brain Abscess; Candidiasis; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Echoencephalography; Female; Flucytosine; Follow-Up Studies; Fungemia; Humans; Infant; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Magnetic Resonance Imaging

The prevalence of fungemia due to non-albicans Candida species is increasing currently. However, there is no reported case of fungemia due to Candida famata in a burn unit. This retrospective study was aimed to evaluate the clinical and laboratory characteristics and outcomes of seven burn patients with fungemia due to C. famata. The study included a total of 410 burn patients followed-up during January 2003-January 2006. Six of the patients (85.7%) were males and one was female (14.3%), with a mean age of 22.2 years. Mean total body surface area of the burns was 39.2% (24%-64%), flame being the most frequent cause of the burns (n= 4), followed by hot water (n= 2) and electroshock (n= 1). Six of the cases had central venous catheter and in 5 of these catheter-associated bacteremia had developed before the establishment of candidemia. Pseudomonas aeruginosa (n= 5) was the most frequent cause of bacteremia; Escherichia coil being isolated from a patient with urinary tract infection and methicillin-resistant Staphylococcus aureus from a patient with wound infection. All patients had received treatment with systemic antibiotics prior to the development of the C. famata episode. C. famata was detected from the blood cultures of the patients, however, the wound swabs were negative in terms of C. famata growth. The isolates were defined according to their negative germ tube test and their carbohydrate assimilation profile in API 20 C AUX (BioMerieux, France). Since the environmental cultures yielded negative results for C. famata, the infections were thought to be derived from cross contamination. Once a positive blood culture for C. famata was obtained, the catheter was removed, and treatment with liposomal amphotericin-B was implemented. Presence of a central venous catheter and prior antibiotic therapy seem to be the predisposing factors in the development of fungemia due to C. famata. Thus, when fungemia due to C. famata is established, central venous catheter should be removed and amphotericin-B therapy should be implemented promptly.

Topics: Amphotericin B; Antifungal Agents; Burn Units; Burns; Candida; Candidiasis; Catheterization, Central Venous; Female; Fungemia; Humans; Male; Prevalence; Retrospective Studies; Turkey; Young Adult

Voriconazole is used for treating invasive Aspergillosis, Fusarium and Scedosporium infections as well as resistant candidiasis. It is referred to as a second generation triazole. The purpose of this study was to evaluate the concordance of the results of antifungal voriconazole susceptibility tests for yeast isolates, comparing the Sensititre YeastOne method, Atb Fungus 3 and Etest. In all, 138 yeast isolates (42 C. tropicalis, 36 C. glabrata, 14 C. albicans, 8 C. famata, 6 C. parapsilosis, 4 C. dubliniensis, 3 C. krusei, 3 C. lusitaniae, 2 C. zeylanoides, 20 Candida spp.) were tested for susceptibility to amphotericin B, flucytosine, fluconazole , itraconazole and voriconazole with Atb Fungus 3 method. The concordance between the Sensititre YeastOne method, Atm Fungus 3 and Etest for voriconazole was high (90%).

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Drug Resistance, Multiple, Fungal; Fluconazole; Flucytosine; Humans; Itraconazole; Microbial Sensitivity Tests; Pyrimidines; Species Specificity; Triazoles; Voriconazole

Candidemia in the pediatric burn population poses a management dilemma due to the paucity of good clinical data to guide treatment decisions. Whilst candidemia is less common than bacteremia in pediatric burns patients, it is associated with significant morbidity and mortality. We report a case of candidemia in an infant with 40% burns with ophthalmic complications secondary to nappy rash. We review the investigation and management of ocular candidemia.

Topics: Amphotericin B; Anti-Infective Agents; Candidiasis; Endophthalmitis; Female; Humans; Infant; Review Literature as Topic

The purpose of this work was to identify differences in incidence, risk factors, microbiology, treatment, and clinical outcome of candidemia in neonates, children, and adults that might impact on management.. Cases of candidemia in Australia were identified prospectively by blood culture surveillance over 3 years. Episodes of candidemia in neonatal, pediatric, and adult age groups were analyzed and compared.. Of 1005 incident cases, 33 occurred in neonates, 110 in children, and 862 in adults. The respective annual age-specific incidences were 4.4, 0.9, and 1.8 per 100,000 population. Prematurity and ICU admission were major risk factors in neonates. Hematologic malignancy and neutropenia were significantly more frequent in children than in neonates and adults. Diabetes, renal disease, hemodialysis, and recent surgery were more common in adults. Candidemia was attributed to a vascular access device in 58% of neonates, 70% of children, and 44% of adults. Candida albicans caused approximately 48% of cases in all of the age groups. Candida parapsilosis was significantly more common in neonates and children (42% and 38% vs 15%). Candida glabrata was infrequent in neonates and children (9% and 3% vs 17%). Significantly more isolates from children were susceptible to fluconazole compared with those from adults (95% vs 75%). Fluconazole-resistant candidal isolates were infrequent in all of the age groups. Neonates and children were more likely to receive amphotericin B compared with adults. Adults were more likely to receive fluconazole. Survival rates at 30 days were 78% in neonates, 90% in children, and 70% in adults.. This study identifies significant differences in candidemia in neonates, children, and adults. Neonatologists and pediatricians must consider age-specific differences when interpreting adult studies and developing treatment and prevention guidelines.

Topics: Adult; Amphotericin B; Antifungal Agents; Australia; Candida albicans; Candidiasis; Child; Child, Preschool; Comorbidity; DNA Fingerprinting; Female; Fluconazole; Humans; Incidence; Infant, Newborn; Infant, Premature; Male; Neoplasms; Risk Factors; Seroepidemiologic Studies; Systemic Inflammatory Response Syndrome

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Catheter-Related Infections; Catheterization, Central Venous; Cross Infection; Drug Therapy, Combination; Echinocandins; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Lipopeptides

Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing.. Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis.. The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher than the incidence of candidemia caused by C. albicans (45.6%). The overall, crude 12-week mortality rate was 35.2%. Patients with Candida parapsilosis candidemia had the lowest mortality rate (23.7%; P<.001) and were less likely to be neutropenic (5.1%; P<.001) and to receive corticosteroids (33.5%; P<.001) or other immunosuppressive drugs (7.9%; P=.002), compared with patients infected with other Candida species. Candida krusei candidemia was most commonly associated with prior use of antifungal agents (70.6%; P<.001), hematologic malignancy (52.9%; P<.001) or stem cell transplantation (17.7%; P<.001), neutropenia (45.1%; P<.001), and corticosteroid treatment (60.8%; P<.001). Patients with C. krusei candidemia had the highest crude 12-week mortality in this series (52.9%; P<.001). Fluconazole was the most commonly administered antimicrobial, followed by the echinocandins, and amphotericin B products were infrequently administered.. The epidemiology and choice of therapy for candidemia are rapidly changing. Additional study is warranted to differentiate host factors and differences in virulence among Candida species and to determine the best therapeutic regimen.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Child; Child, Preschool; Cross Infection; Echinocandins; Female; Fluconazole; Fungemia; Humans; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Survival Analysis; Treatment Outcome; Young Adult

We established a murine model of Candida albicans central nervous system (CNS) infection and evaluated the efficacy of anidulafungin. Ten milligrams/kg/day anidulafungin, amphotericin B, or voriconazole significantly reduced mortality and fungal burden in brain tissue, although amphotericin B and 10 mg/kg/day anidulafungin reduced fungal burden in brain tissue to a greater extent than did voriconazole. This suggests a potential role for anidulafungin in the treatment of candidal CNS infection.

Topics: Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Candida albicans; Candidiasis; Central Nervous System Infections; Disease Models, Animal; Echinocandins; Female; Mice; Pyrimidines; Triazoles; Voriconazole

To describe changes in demographics and pathogens for fungal keratitis cases diagnosed at the Massachusetts Eye and Ear Infirmary.. Patient demographics, clinical and laboratory findings, treatment and outcomes of 46 cases of culture-proven fungal keratitis diagnosed from January 2004 through November 2007 were compared with 23 cases of fungal keratitis previously collected over a similar period from January 1999 through November 2002.. During 2004-2007, the rate of fungal keratitis was 1.0 cases per month, an increase from the baseline rate of 0.5 cases per month during 1999-2002. The proportion of cases caused by filamentous fungi increased from 30% (1999-2002) to 65% (2004-2007) (P = 0.01). Soft contact lens wear accounted for 41% of fungal keratitis cases in 2004-2007, as compared with 17% in 1999-2002. The majority of patients (70%) received oral antifungal treatment in addition to topical amphotericin B and natamycin. Seventeen patients (40%) required therapeutic keratoplasty. Patients with a history of corneal transplant had the highest rate of therapeutic keratoplasties (67%) and had the poorest visual outcome (40% counting fingers or less). In the contact lens group, 94% of patients maintained vision of at least 20/40 and only 12% required surgery to control the infection.. There has been an increase in fungal keratitis in the Boston area and a change in the causative pathogens and risk factors for infection. Filamentous fungi now account for the majority of fungal keratitis cases, whereas yeasts were the predominant pathogen in the past. Soft contact lens wear is currently the most common risk factor for development of fungal keratitis.

Topics: Administration, Oral; Administration, Topical; Adult; Aged; Alternaria; Amphotericin B; Antifungal Agents; Boston; Candidiasis; Cohort Studies; Contact Lenses; Corneal Transplantation; Drug Therapy, Combination; Eye Infections, Fungal; Female; Fusarium; Humans; Incidence; Keratitis; Male; Middle Aged; Natamycin; Retrospective Studies; Risk Factors; Treatment Outcome

Invasive candidiasis is associated with high morbidity and mortality. Differences in the virulence and susceptibility of the various Candida spp. to antifungal drugs make the identification and rapid MIC determination very important for clinical management. The aim of this study was to improve the turnaround time (TAT) for antimicrobial test generation by susceptibility testing directly from the bottle of blood culture positive for yeasts, circumventing the isolation process and thereby generating an accurate antifungal MIC determination as quickly as possible. Sensititre YeastOne was used by direct inoculation from positive blood culture bottles in 40 cases of candidaemia. All the results were compared with those obtained using standard laboratory procedures after subculturing from a positive bottle onto solid media. The results obtained from direct inoculation of Sensititre YeastOne compared with tests carried out using standard procedures show that out of a total of 40 strains tested no very major errors or major errors and only 4 minor errors occurred (98% agreement rate out of a total of 240 drug/bug combinations tested), thus generating an accurate antifungal MIC determination and saving an average time of 24 hours compared with the time required for the standard procedures traditionally used.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Fluconazole; Flucytosine; Humans; Itraconazole; Ketoconazole; Microbial Sensitivity Tests; Pyrimidines; Reagent Kits, Diagnostic; Sensitivity and Specificity; Time Factors; Triazoles; Voriconazole

A 72-year-old man was admitted to our hospital because of a low grade fever and malaise. He had received a middle to lower esophagectomy and proximal gastrectomy with reconstruction of a gastric conduit for esophageal cancer 12 years previously. Chest X-ray and CT scan revealed massive pleural effusion and consolidations on the right side. Candida glabrata was isolated 4 times from pleural fluid specimens. Candida antigen was negative in both serum and pleural effusion. However, while serum beta-D-glucan was negative, the level of beta-D-glucan in pleural effusion was extremely elevated. Thus, the patient was diagnosed as having C. glabrata empyema. He was treated with insertion of a thoracostomy tube followed by intrapleural instillation of amphotericin B and intravenous administration of micafungin. Pleural effusion was reduced and the repeated culture of the pleural effusion became negative after 27 days of treatment. Empyema with C. glabrata is rare and the present case is the second report of the disease in the Japanese literature.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Echinocandins; Empyema; Humans; Lipopeptides; Male; Micafungin; Thoracostomy

Amphotericin B microspheres (M-AMB) are a new, inexpensive formulation of amphotericin B. In this study, we tested the efficacy of this new formulation for treating murine disseminated infections by Candida glabrata or Candida tropicalis. M-AMB showed a similar efficacy to that of amphotericin B deoxycholate and liposomal amphotericin B in the treatment of both disseminated murine infections. Its low toxicity and inexpensive production costs make this formulation potentially attractive for the treatment of fungal infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida glabrata; Candida tropicalis; Candidiasis; Chemistry, Pharmaceutical; Female; In Vitro Techniques; Male; Mice; Microspheres; Survival Analysis; Treatment Outcome

To report the first successful use of anidulafungin and liposomal amphotericin B in an infant with peritoneal candidiasis.. An 11-day-old term female infant with Hirschsprung enterocolitis and bowel perforation was transferred to our institution on day 4 of hospitalization with septic shock and abdominal compartment syndrome. Initial peritoneal culture at time of colectomy did not grow yeast; however, Candida albicans grew from cultures obtained on abdominal washout 2 days later even while the patient was on treatment with liposomal amphotericin B 5 mg/kg/day. Anidulafungin 1.5 mg/kg/day intravenous therapy was instituted, and within 4 days peritoneal cultures were negative. The patient slowly recovered and, after a prolonged hospitalization, she was discharged home on hospital day 68 on partial parenteral nutrition.. Despite the rising incidence of fluconazole-resistant Candida spp., pediatric dosing guidelines, and an adult indication for echinocandin use in candidal peritonitis, there are no reports of echinocandin use for fungal peritonitis in pediatric patients. The echinocandins are rational choices when fluconazole resistance is a concern. Furthermore, the unique clearance profile of anidulafungin makes it an attractive choice in critically ill patients with hepatic and renal dysfunction; the Infectious Diseases Society of America has recommended that an echinocandin be first-line antifungal therapy for moderately or severely ill pediatric or adult patients.. Peritoneal candidiasis is a common complication of bowel perforation in neonates. Anidulafungin's pharmacokinetic and antifungal properties make it a viable therapeutic option in the treatment of this disease in critically ill infants and children.

Topics: Amphotericin B; Anidulafungin; Candidiasis; Drug Therapy, Combination; Echinocandins; Female; Humans; Infant, Newborn; Peritoneal Cavity; Treatment Outcome

The prevalence of nephrotoxicity in neonates receiving amphotericin B deoxycholate (amphoB) is not well-defined. While some studies report a lack of toxicity, others claim a frequency as high as 85%.. We reviewed medical records of all infants < or = 90 days of age in the neonatal intensive care unit who received at least 3 doses of amphoB between January 1990 and December 2004. A standardized form was used to collect demographic, therapeutic, microbiologic, and laboratory data for each patient. Nephrotoxicity was defined as a rise in serum creatinine (SCr) of at least 0.4 mg/dL any time during amphoB therapy.. A total of 92 infants met entry criteria. Median gestational age was 26 (range: 23-41) weeks and median birth weight was 863 (range: 546-4000) grams. Overall, 15 (16%) infants experienced nephrotoxicity, and 16 (17%) developed hypokalemia (<3.0 mmol/L). There were no differences between infants who did or did not develop nephrotoxicity in terms of gestational age, birth weight, gender, underlying medical conditions, or use of other potentially nephrotoxic medications. AmphoB exposure and duration of therapy were similar between infants who developed nephrotoxicity and those who did not, with a mean cumulative dose of 13.5 +/- 9.6 mg/kg and duration of 16.3 +/- 10.4 days. With the exception of 1 infant, the elevated SCr values resolved in all infants by the end of amphoB therapy.. AmphoB administration does not appear to be associated with lasting measurable nephrotoxicity in neonates. Because of changes in serum creatinine and potassium, renal function and potassium levels should be monitored closely in infants receiving amphoB.

Topics: Amphotericin B; Candidiasis; Creatinine; Deoxycholic Acid; Drug Combinations; Humans; Infant, Newborn; Kidney; Kidney Diseases; Retrospective Studies; Statistics, Nonparametric

The authors report on a case of intracranial candidiasis in an immunocompetent neonate with a ventriculo-peritoneal shunt. The child was known to be colonized with yeast as she had been treated for oral thrush; however, she did not have systemic candidiasis. Despite initial treatment with antifungal medication, intraventricular fungus balls developed that were visible on imaging and confirmed with pathological analysis. Multiple endoscopic intraventricular operations were required for excision of the initial and recurrent fungus balls, multiple fenestrations of loculations and cysts were performed, and ultimately 3 ventriculoperitoneal shunts were placed. The finding of an intraventricular fungus ball is a unique manifestation of intracranial candidiasis, and to the authors' knowledge has not been previously reported in the English literature.

Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Brain Diseases; Candidiasis; Caspofungin; Echinocandins; Endoscopy; Ependyma; Female; Fluconazole; Humans; Immunocompetence; Infant, Newborn; Injections, Spinal; Lipopeptides; Magnetic Resonance Imaging; Postoperative Care; Recurrence; Reoperation; Ventriculoperitoneal Shunt

The aim of this study was to evaluate the treatment options of experimental in-vivo Candida endophthalmitis. For inoculation, a 0.1 ml of suspension of Candida albicans was injected into the vitreous of the right eye of each New Zealand rabbit. On the 15th day, the clinical evaluation for the resultant endophthalmitis was noted, and vitreous samples were obtained. On the 21st day, culture positive eyes were divided into four groups in terms of treatment modalities. Group 1 (n = 7) received intravitreal amphotericin B injection, group 2 (n = 8) received both intravitreal dexamethasone and amphotericin B injections, group 3 (n = 8) underwent pars plana vitrectomy (PPV) and amphotericin B injection, and group 4 (n = 8) underwent PPV and both amphotericin B and silicone oil injections. The vitreous samples obtained from right eyes of the rabbits on the 15th day, were all culture positive for Candida albicans. On the 35th day, the least colony counts (colony forming unit) were present in eyes that received only intravitreal amphotericin B injection in group 1, followed by group 4 that underwent PPV and both amphotericin B and silicone oil injections. In Candida endophthalmitis, intravitreal injection of amphotericin B without steroid appears to be the primary choice of therapy. In cases who fail to respond to this regimen alone, PPV in combination with silicone oil injection may be considered. Benefit-risk ratio should be cautiously interpreted for application of intravitreal steroid injection.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Dexamethasone; Disease Models, Animal; Endophthalmitis; Glucocorticoids; Injections, Intraocular; Male; Rabbits; Risk Assessment; Silicone Oils; Vitrectomy; Vitreous Body

Candidemia is an opportunistic infection caused primarily by Candida albicans. We experienced a case of severe Candidemia that developed after surgical treatment for tongue cancer and required considerable labor to diagnose and to treat, though no particular immunodeficiency was seen before. The case was resistant to an antifungal agent, fluconazole, but was successfully treated with amphotericin B. Positive blood cultures, local wound culture, and increased β;-D-glucan were useful to diagnose the infection. In particular, gallium-67 scintigraphy was remarkably useful for the diagnosis and the evaluation of therapeutic effects in this case. Development of Candidemia following an oral and maxillofacial surgery is extremely rare among young adults, thus this case report serves to draw attention to the risk in oral and maxillofacial surgery.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Drug Resistance, Fungal; Fluconazole; Gallium Radioisotopes; Humans; Postoperative Complications; Radionuclide Imaging; Tongue Neoplasms; Treatment Outcome; Young Adult

We evaluated the effects of sequential therapy with caspofungin (CAS) or amphotericin B (AMB) followed by posaconazole (POS) against Candida glabrata. The susceptibilities to POS of yeast cells pre-exposed to CAS or AMB were identical to those of untreated cells as shown by standard Clinical and Laboratory Standards Institute broth dilution, cell viability, and disk diffusion methods. We then investigated the activity of sequential regimens in an experimental model of disseminated candidiasis. CAS given at 1 mg/kg/day for 2 days followed by POS at either 15 or 30 mg/kg/day significantly reduced the counts compared to the controls, but this treatment was not superior to the use of CAS alone. Also, sequential regimens with AMB given at 1 mg/kg/day for 2 days followed by POS (AMB/POS) were effective at reducing the fungal burden against the controls. In addition, AMB/POS with both doses of the triazole were significantly more effective than AMB alone. Overall, our data showed that there is no therapeutic advantage in using CAS followed by POS, whereas an induction therapy with AMB followed by a maintenance regimen with POS might be a suitable strategy in managing C. glabrata infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Colony Count, Microbial; Drug Administration Schedule; Echinocandins; Humans; Kidney; Lipopeptides; Male; Mice; Microbial Sensitivity Tests; Treatment Outcome; Triazoles

Omiganan, a bactericidal and fungicidal cationic peptide being developed as a topical gel for prevention of catheter-associated infections, inhibited commonly occurring fungal pathogens including Candida spp. (106 isolates) at

Topics: Antifungal Agents; Antimicrobial Cationic Peptides; Aspergillosis; Aspergillus; Candida; Candidiasis; Catheterization, Central Venous; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Fungemia; Fungi; Humans; Microbial Sensitivity Tests

The in vitro and in vivo antifungal activities of T-2307, a novel arylamidine, were evaluated and compared with those of fluconazole, voriconazole, micafungin, and amphotericin B. T-2307 exhibited broad-spectrum activity against clinically significant pathogens, including Candida species (MIC range, 0.00025 to 0.0078 microg/ml), Cryptococcus neoformans (MIC range, 0.0039 to 0.0625 microg/ml), and Aspergillus species (MIC range, 0.0156 to 4 microg/ml). Furthermore, T-2307 exhibited potent activity against fluconazole-resistant and fluconazole-susceptible-dose-dependent Candida albicans strains as well as against azole-susceptible strains. T-2307 exhibited fungicidal activity against some Candida and Aspergillus species and against Cryptococcus neoformans. In mouse models of disseminated candidiasis, cryptococcosis, and aspergillosis, the 50% effective doses of T-2307 were 0.00755, 0.117, and 0.391 mg.kg(-1).dose(-1), respectively. This agent was considerably more active than micafungin and amphotericin B against candidiasis and than amphotericin B against cryptococcosis, and its activity was comparable to the activities of micafungin and amphotericin B against aspergillosis. The results of preclinical in vitro and in vivo evaluations performed thus far indicate that T-2307 could represent a potent injectable agent for the treatment of candidiasis, cryptococcosis, and aspergillosis.

Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Benzamidines; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Mycoses; Specific Pathogen-Free Organisms; Treatment Outcome

We describe the prevalences and susceptibility profiles of two recently described species, Candida metapsilosis and Candida orthopsilosis, related to Candida parapsilosis in candidemia. The prevalences of these species (1.7% for C. metapsilosis and 1.4% for C. orthopsilosis) are significant. Differences observed in their susceptibility profiles could have therapeutic importance.

Topics: Antifungal Agents; Candida; Candidiasis; Fungemia; Humans; Microbial Sensitivity Tests; Population Surveillance; Prevalence; Spain; Species Specificity

We describe a case of recurring Candida glabrata infection in a 68-year-old African-American female on caspofungin therapy. The initial isolate was susceptible, but isolates recovered during following relapses were not. All isolates were clonal, and high-MIC strains contained a mutation in the highly conserved hot spot 1 region of Fks1p.

Topics: Aged; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Drug Resistance, Fungal; Echinocandins; Fatal Outcome; Female; Fungal Proteins; Fungemia; Glucosyltransferases; Humans; Lipopeptides; Membrane Proteins; Microbial Sensitivity Tests; Mutation

We tested the activity of anidulafungin against 30 Candida albicans isolates. The planktonic MICs for 50 and 90% of the isolates tested (MIC(50) and MIC(90)) were < or =0.03 and 0.125 microg/ml, respectively (MIC range, < or =0.03 to 2 microg/ml). The sessile MIC(50) and MIC(90) were < or =0.03 and < or =0.03 microg/ml, respectively (MIC range, < or =0.03 to >16 microg/ml).

Topics: Anidulafungin; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Drug Resistance, Fungal; Echinocandins; Humans; Microbial Sensitivity Tests

We investigated the in vitro activities of posaconazole (POS), fluconazole (FLC), amphotericin B (AMB), and caspofungin (CAS) against four clinical isolates of Candida glabrata with various susceptibilities to FLC (FLC MICs ranging from 1.0 to >64 microg/ml). POS MICs ranged from < or =0.03 to 0.5 microg/ml; AMB MICs ranged from 0.25 to 2.0 microg/ml, while CAS MICs ranged from 0.03 to 0.25 microg/ml. When FLC MICs increased, so did POS MICs, although we did not observe any isolate with a POS MIC greater than 0.5 mug/ml. Time-kill experiments showed that POS, FLC, and CAS were fungistatic against all isolates, while AMB at eight times the MIC was fungicidal against three out of four isolates of C. glabrata tested. Then, we investigated the activity of POS in an experimental model of disseminated candidiasis using three different isolates of C. glabrata: one susceptible to FLC (S; FLC MICs ranging from 1.0 to 4.0 microg/ml; POS MIC of < or =0.03 microg/ml), one susceptible in a dose-dependent manner (SDD; FLC MICs ranging from 32 to 64 microg/ml; POS MICs ranging from 0.125 to 0.25 microg/ml), and another one resistant to FLC (R; FLC MIC of >64 microg/ml; POS MIC of 0.5 microg/ml). FLC significantly reduced the kidney burden of mice infected with the S strain (P = 0.0070) but not of those infected with the S-DD and R strains. POS was significantly effective against all three isolates at reducing the kidney fungal burden with respect to the controls (P ranging from 0.0003 to 0.029). In conclusion, our data suggest that POS may be a useful option in the management of systemic infections caused by C. glabrata. Additionally, the new triazole may be a therapeutic option in those cases where an FLC-resistant isolate is found to retain a relatively low POS MIC.

Topics: Animals; Antifungal Agents; Candida glabrata; Candidiasis; Drug Resistance, Fungal; Fluconazole; Humans; Kidney; Male; Mice; Microbial Sensitivity Tests; Treatment Outcome; Triazoles

Unlike the molecular mechanisms that lead to azole drug resistance, the molecular mechanisms that lead to polyene resistance are poorly documented, especially in pathogenic yeasts. We investigated the molecular mechanisms responsible for the reduced susceptibility to polyenes of a clinical isolate of Candida glabrata. Sterol content was analyzed by gas-phase chromatography, and we determined the sequences and levels of expression of several genes involved in ergosterol biosynthesis. We also investigated the effects of the mutation harbored by this isolate on the morphology and ultrastructure of the cell, cell viability, and vitality and susceptibility to cell wall-perturbing agents. The isolate had a lower ergosterol content in its membranes than the wild type, and the lower ergosterol content was found to be associated with a nonsense mutation in the ERG6 gene and induction of the ergosterol biosynthesis pathway. Modifications of the cell wall were also seen, accompanied by increased susceptibility to cell wall-perturbing agents. Finally, this mutation, which resulted in a marked fitness cost, was associated with a higher rate of cell mortality. Wild-type properties were restored by complementation of the isolate with a centromeric plasmid containing a wild-type copy of the ERG6 gene. In conclusion, we have identified the molecular event responsible for decreased susceptibility to polyenes in a clinical isolate of C. glabrata. The nonsense mutation detected in the ERG6 gene of this isolate led to a decrease in ergosterol content. This isolate may constitute a useful tool for analysis of the relevance of protein trafficking in the phenomena of azole resistance and pseudohyphal growth.

Topics: Antifungal Agents; Azoles; Base Sequence; Candida glabrata; Candidiasis; Codon, Nonsense; DNA, Fungal; Drug Resistance, Fungal; Ergosterol; Genes, Fungal; Guanine; Humans; Molecular Sequence Data; Polyenes

Candida inconspicua is an emerging pathogen in immunocompromised patients possessing inherently decreased susceptibility to fluconazole. We determined the MICs and killing activity of fluconazole and amphotericin B against C. inconspicua clinical isolates as well as reference strain C. inconspicua ATCC 16783 for comparison. MICs were determined using the standard broth microdilution method. Killing rates were determined using time-kill methodology at 0.5-16 x MIC fluconazole and amphotericin B concentrations. Fluconazole and amphotericin B MIC values varied between 16-128 mg/l and 0.5-1 mg/l, respectively. In time kill-assays fluconazole showed fungistatic effect at 1-16 x MIC concentrations against all tested strains after 24 h-incubation, but became fungicidal after 48 h at 4-16 x MIC concentrations. The time necessary to achieve fungicidal endpoint at 1 mg/l amphotericin B concentration ranged from 2 to 24 h. Our in vitro results confirm the data that fluconazole is ineffective against C. inconspicua at the fluconazole serum concentration attainable in humans. Amphotericin B due to its rapid killing activity seems to be a good alternative for the treatment of infections caused by C. inconspicua.

Topics: Amphotericin B; Candida; Candidiasis; Fluconazole; Humans; Microbial Sensitivity Tests; Microbial Viability; Time Factors

The case is presented of a native valve endocarditis caused by Candida sake in a 34-year-old farmer with no history of intravenous drug abuse or pre-existing valvular abnormality. The patient presented with septicemia and multiorgan dysfunction syndrome (MODS). Clinical and diagnostic work-up revealed findings of severe aortic regurgitation and large vegetations on the aortic valve. Preoperatively, the patient was treated for three weeks with amphotericin B; when the MODS had improved, open-heart surgery with valve replacement was performed. Intravenous amphotericin B was continued postoperatively for three more weeks; a subsequent decision was taken to administer lifelong suppressive antifungal therapy.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Candidiasis; Echocardiography, Transesophageal; Endocarditis, Bacterial; Humans; Male

A new poly-aggregated form of amphotericin B was formulated as a non-microencapsulated form (P-AMB) or incorporated in albumin microspheres (MP-AMB) and compared with the conventional amphotericin B formulation (D-AMB). Mice were infected with Candida albicans and treated with two different intermittent dose regimens of the different amphotericin B formulations. Efficacy and toxicity were studied by the determination of survival rate, kidney colony-forming units counts, biochemical parameters and amphotericin B concentrations in plasma and organs. All the treatments significantly (P<0.05) increased the survival rate in relation to the untreated group, although non-statistically significant differences (P>0.05) were found between formulations and dosing regimens. All the treatments produced kidney toxicity, expressed by high urea levels. Kidney toxicity was especially significant for mice treated with the D-AMB formulation where unilateral kidney atrophy was observed in most of the mice, whereas most of the mice treated with P-AMB conserved both kidneys with a normal size and appearance. At 45 days post infection, variable distribution of amphotericin B in the body was obtained depending on the amphotericin B formulation. In conclusion, non-daily dosing regimens of P-AMB, which is less toxic than D-AMB, could be used as an alternative to the conventional D-AMB formulation to treat experimental candidiasis.

Topics: Amphotericin B; Animal Structures; Animals; Antifungal Agents; Atrophy; Candida albicans; Candidiasis; Chemistry, Pharmaceutical; Female; Kidney; Mice; Mice, Inbred ICR; Plasma; Survival Analysis

During a 3-year surveillance program (2004 to 2007) in Monterrey, Mexico, 398 isolates of Candida spp. were collected from five hospitals. We established the species distribution and in vitro susceptibilities of these isolates. The species included 127 Candida albicans strains, 151 C. parapsilosis strains, 59 C. tropicalis strains, 32 C. glabrata strains, 11 C. krusei strains, 5 C. guilliermondii strains, 4 C. famata strains, 2 C. utilis strains, 2 C. zeylanoides strains, 2 C. rugosa strains, 2 C. lusitaniae strains, and 1 C. boidinii strain. The species distribution differed with the age of the patients. The proportion of candidemias caused by C. parapsilosis was higher among infants 45 years old). MICs were calculated following the criteria of the Clinical Laboratory Standards Institute reference broth macrodilution method. Overall, C. albicans, C. parapsilosis, and C. tropicalis isolates were susceptible to fluconazole and amphotericin B. However, 31.3% of C. glabrata isolates were resistant to fluconazole (MIC >or= 64 microg/ml), 43.3% were resistant to itraconazole (MIC >or= 1 microg/ml), and 12.5% displayed resistance to amphotericin B (MIC >or= 2 microg/ml). Newer triazoles, namely, voriconazole, posaconazole, and ravuconazole, had a notable in vitro activity against all Candida species tested. Also, caspofungin was active against Candida sp. isolates (MIC(90)

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candida tropicalis; Candidiasis; Caspofungin; Child; Child, Preschool; Echinocandins; Female; Fluconazole; Humans; Infant; Infant, Newborn; Itraconazole; Lipopeptides; Male; Mexico; Microbial Sensitivity Tests; Middle Aged; Pyrimidines; Thiazoles; Triazoles; Voriconazole; Young Adult

The current standard of care for a fungal central venous catheter infection in a pediatric patient usually requires removal without any other feasible options. Although removal may reduce the rate of Candida-associated complications, literature reviews question whether the outcomes of removal substantiate this being the standard of care. We report 6 cases of central venous catheter fungal infections treated with liposomal amphotericin-B lock therapy. These cases consisted of 4 patients, 2 of whom received recurrent therapy. In 4 of these cases, there was successful eradication of the infectious fungal agent, allowing continued use of the catheter. A controlled study of antifungal lock therapy should be considered as a potential alternative to removal.

Topics: Amphotericin B; Antifungal Agents; Blood; Candida albicans; Candida glabrata; Candidiasis; Catheterization, Central Venous; Child; Culture Media; Female; Fungemia; Humans; Infant; Liposomes; Male; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Fluconazole; Humans; South Africa

The treatment, diagnosis and therapeutic monitoring of hematogenous Candida meningoencephalitis (HCME) are not well understood. We therefore studied the expression of (1-->3)-beta-D-glucan (beta-glucan) in cerebrospinal fluid (CSF) and plasma in a nonneutropenic rabbit model of experimental HCME treated with micafungin and amphotericin B. Groups studied consisted of micafungin (0.5 to 32 mg/kg) and amphotericin B (1 mg/kg) treatment groups and the untreated controls (UC). Despite well-established infection in the cerebrum, cerebellum, choroid, vitreous humor (10(2) to 10(3) CFU/ml), spinal cord, and meninges (10 to 10(2) CFU/g), only 8.1% of UC CSF cultures were positive. By comparison, all 25 UC CSF samples tested for beta-glucan were positive (755 to 7,750 pg/ml) (P < 0.001). The therapeutic response in CNS tissue was site dependent, with significant decreases of the fungal burden in the cerebrum and cerebellum starting at 8 mg/kg, in the meninges at 2 mg/kg, and in the vitreous humor at 4 mg/kg. A dosage of 24 mg/kg was required to achieve a significant effect in the spinal cord and choroid. Clearance of Candida albicans from blood cultures was not predictive of eradication of organisms from the CNS; conversely, beta-glucan levels in CSF were predictive of the therapeutic response. A significant decrease of beta-glucan concentrations in CSF, in comparison to that for UC, started at 0.5 mg/kg (P < 0.001). Levels of plasma beta-glucan were lower than levels in simultaneously obtained CSF (P < 0.05). CSF beta-glucan levels correlated in a dose-dependent pattern with therapeutic responses and with Candida infection in cerebral tissue (r = 0.842). Micafungin demonstrated dose-dependent and site-dependent activity against HCME. CSF beta-glucan may be a useful biomarker for detection and monitoring of therapeutic response in HCME.

Topics: Amphotericin B; Animals; Antifungal Agents; beta-Glucans; Biomarkers; Candidiasis; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Monitoring; Echinocandins; Female; Lipopeptides; Meningitis, Fungal; Meningoencephalitis; Micafungin; Rabbits

The indirect impact of the known comparator drug in double-blind comparative clinical trials of novel agents is underappreciated, despite its potentially pernicious effects. This hypothesis-generating analysis illustrates potential spillover effects of a comparator (amphotericin) in the evaluation of the first member (caspofungin) of a novel class (echinocandins) of antifungal drugs. Reported rates of drug-related fever in the first 3 studies of caspofungin for the treatment of mucosal candidiasis in patients with advanced human immunodeficiency virus infection were retrospectively analyzed. We compared patients who received 50 mg of caspofungin per day in a double-blind trial that used fluconazole as the comparator with patients who received the corresponding dosage in 2 similar earlier studies that used amphotericin as the comparator. With respect to the incidence of drug-related fever, the difference between the concurrent caspofungin and fluconazole groups was less than the difference between caspofungin groups from studies that used different comparators. In phase II/III blinded, active-control trials, the reporting of adverse experiences attributed to a first-in-class drug might be confounded to a variable degree by expectations regarding a well-known comparator.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Double-Blind Method; Echinocandins; Fever; Fluconazole; HIV Infections; Humans; Lipopeptides; Randomized Controlled Trials as Topic

The susceptibility of 1763 yeast isolates (from 22 species and seven genera) was tested using Clinical and Laboratory Standards Institute M27-A2 microdilution methodology. Candida spp. predominated (97.1%), mainly C. albicans (51.4%), C. glabrata (16.4%) and C. tropicalis (13.7%), followed by Trichosporon spp. (1.1%) and Cryptococcus neoformans (1.0%). Most isolates came from blood/catheters (72.0%) or the oesophagus/oropharynx (11.3%). The voriconazole, itraconazole, fluconazole and amphotericin B MIC90 values (minimum inhibitory concentration for 90% of the isolates) for all isolates were 1.0, 2.0, 64 and 1.0 microg/mL, respectively. Voriconazole MICs correlated with those for fluconazole (r = 0.91) and itraconazole (r = 0.90). Only 109 isolates (6.2%) had voriconazole MICs > or = 4.0 microg/mL; all were C. albicans, C. glabrata or C. tropicalis resistant to itraconazole (and most to fluconazole). Isolates from 22 patients with amphotericin MICs > or = 2.0 microg/mL (range 2.0-16.0 microg/mL) were also cross-resistant to one or more of the triazoles. Patients (n = 34) with voriconazole-resistant isolates showed a 56% response to voriconazole therapy, and those patients (n = 261) with susceptible isolates showed a 71% response. Twenty-three voriconazole-treated patients had baseline resistant isolates, in eight patients voriconazole resistance developed during therapy and in three patients a different resistant species arose during therapy. Thus, voriconazole MICs correlate with those of fluconazole and itraconazole and may predict clinical outcome.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Clinical Trials, Phase III as Topic; Fluconazole; Humans; Itraconazole; Microbial Sensitivity Tests; Mycoses; Pyrimidines; Triazoles; Voriconazole; Yeasts

Only a handful of cases of human Candida lambica infections have been published up to now. We report a Candida lambica fungemia in a young intravenous drug abuser. Using a popular chromogenic agar and a commercial phenotyping gallery, the fungus was initially misidentified as Candida krusei. Key tests to distinguish these closely related species are maximum growth temperature and assimilation of certain substrates present in more elaborate phenotyping assays. Definite confirmation is possible using molecular techniques. Susceptibility testing of the isolate demonstrated amphotericin B (MIC 0.125 microg/ml) susceptible, flucytosine (MIC 2 microg/ml) susceptible, itraconazole (MIC 0.064 microg/ml) susceptible, voriconazole (MIC 1 microg/ml) susceptible, and fluconazole (MIC >64 microg/ml, resistant).

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Diagnostic Errors; Drug Resistance, Fungal; Fluconazole; Fungemia; Humans; Male; Microbial Sensitivity Tests; Mycological Typing Techniques; Polymerase Chain Reaction; Substance Abuse, Intravenous; Young Adult

To report a case of fungal sepsis treated prospectively with liposomal amphotericin, caspofungin, and a novel monoclonal antibody specific for candidal heat shock protein 90 (Mycograb, Neutec Pharma, Manchester, UK).. Case report.. Pediatric intensive care unit in a tertiary care children's hospital.. A 7-yr-old male with a history of global developmental delay, epilepsy, and gastroesophageal reflux, who presented to the emergency department with a transdiaphragmatic herniation of bowel and subsequent Candida glabrata infection.. Efungumab 1 mg/kg twice daily for 5 days.. C-reactive protein fell from 225 mg/L to 99 mg/L, and physiological monitoring parameters improved when Mycograb was used in conjunction with high-dose antifungals.. Mycograb therapy was well tolerated, but further experience with this therapy in children is needed.

Topics: Amphotericin B; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Child; Critical Illness; Drug Therapy, Combination; Echinocandins; Hernia, Diaphragmatic; HSP90 Heat-Shock Proteins; Humans; Lipopeptides; Male; Postoperative Complications; Recombinant Proteins; Sepsis

The aim of this study was to assess species distribution, antifungal susceptibility and clonal relationships among Candida strains isolated from a group of pediatric/neonatal intensive care (PICU/NICU) patients that had a very high mortality rate (76%). The cases of 21 patients (19 with candidemia, 2 with Candida meningitides) treated over a 1-year period in a Turkish hospital PICU and NICU were retrospectively analyzed. Twenty-eight Candida isolates were detected from blood (20), cerebrospinal fluid (CSF) (2) and other specimens (6). Candida species were identified using the API ID 32C System. Susceptibility testing was done (all 28 isolates) for amphotericin B, fluconazole and itraconazole using the broth microdilution method. Arbitrarily primed polymerase chain reaction (AP-PCR) was used for molecular typing of the 3 most common ones; C. albicans (15), C. parapsilosis (6), and C. pelliculosa (4). Electrophoretic karyotyping (EK) was done to check clonal identity obtained by AP-PCR. Of the 20 blood isolates, 8 (40%) were C. albicans, 12 (60%) were non-albicans Candida, and one of the 2 CSF isolates was C. albicans. The overall species distribution was as follows: 15 C. albicans isolates, 6 C. parapsilosis isolates, 4 C. pelliculosa isolates, 2 C. famata isolates and 1 C tropicalis isolate. Amphotericin B had the best antifungal activity with a MIC90 of 0.125 microg/ml, and the rates of susceptibility to fluconazole and itraconazole were 93% and 82%, respectively. AP-PCR revealed 11 genotypes (4 were identical pairs, 7 were distinct) among the 15 C. albicans isolates, 2 genotypes (5 were classified in the same type) among the 6 C. parapsilosis isolates, and 4 separate genotypes for the 4 C. pelliculosa isolates. Karyotyping results correlated well with the AP-PCR findings. As indicated in the previous research, our results confirmed that non-albicans Candida species have become more frequently causative agents for invasive fungal infections in the ICU. Transmission of C. albicans and C. pelliculosa was relatively low, but transmission of C. parapsilosis was high, suggesting that more effective control and very strict treatment protocols are needed for patients having high mortality and invasive fungal infection in ICU.

Topics: Academic Medical Centers; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Child; Child, Preschool; Female; Fluconazole; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Intensive Care Units, Pediatric; Itraconazole; Male; Microbial Sensitivity Tests; Mycological Typing Techniques; Turkey

Although amphotericin B (AMB) has a wide spectrum of activity that encompasses the majority of yeast isolates, there have been recent reports suggesting that some yeast isolates exhibit decreased susceptibility to AMB. However, in vitro AMB susceptibility of yeast species isolates from blood cultures in Korea has not been fully surveyed.. A total of 92 bloodstream yeast isolates from four Korean hospitals, representing 10 Candida species (69 isolates) and 4 non-Candida yeast species (23 isolates) were evaluated. AMB minimum inhibitory concentrations (MICs) were determined by two methods: the CLSI method and Etest. AMB minimum fungicidal concentrations (MFCs) were also determined.. For all 92 yeast isolates, the CLSI method generated a restricted range of MICs (0.125 to 4 microgram/mL) with 3.3% exhibiting MICs > or =2 microgram/mL, and the corresponding MFC values ranged from 0.25 to 8 microgram/mL with 26.1% showing MFCs > or =2 microgram/mL. Etest produced the widest distribution of MICs, ranging from 0.03 to 32 microgram/mL. High AMB MICs (> or =0.38 microgram/mL) by Etest was observed in 34.8% of the isolates: Candida krusei (100%), Candida rugosa (100%), Trichosporon asashii (100%), Candida glabrata (82%), and Yarrowia lipolytica (75%). Etest disclosed that all isolates of Candida guilliermondii, Candida lusitaniae, Candida pelliculosa and Kodamaea ohmeri were highly susceptible to AMB (MIC < or =0.19 microgram/mL).. Our study showed that Etest may be more useful to discriminate yeast isolates with reduced susceptibility to AMB, and some isolates of less common yeast species from Korea may have decreased AMB susceptibilities.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Culture Media; Humans; Korea; Microbial Sensitivity Tests; Reagent Kits, Diagnostic; Yeasts

We report a case of fatal fungal peripheral suppurative thrombophlebitis, caused by Candida albicans, which was disseminated to the blood, lungs, eyes, and spine. Clinical suspicion and aggressive management are important in managing fungal peripheral suppurative thrombophlebitis. Early clinical suspicion is important in managing fungal peripheral suppurative thrombophlebitis, and radical excision of the affected veins, recognition of metastatic foci, and use of systemic antifungal agents are essential to avoid septic shock and death.

Topics: Amphotericin B; Anti-Bacterial Agents; Candida albicans; Candidiasis; Echocardiography; Fatal Outcome; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Postoperative Complications; Rectal Neoplasms; Thrombophlebitis

The emergence of less common fungal pathogens has been increasingly reported in the last decade. We describe 25 cases of Rhodotorula spp. isolated from blood cultures at a large Brazilian tertiary teaching hospital from 1996-2004. We also investigated the in vitro activity of four antifungal drugs, using a standardized method. The median age of patients was 43 years. The majority of patients (88%) had a central venous catheter (CVC) and 10 (40%) were recipients of a bone marrow transplant. The episode was classified as a bloodstream infection (BSI) in 80% of the patients. Amphotericin B deoxycholate was the most common antifungal used and CVC was removed in 89.5% of the patients. Death occurred in four patients (17.4%), all classified as BSI. All strains were identified as R. mucilaginosa by conventional methods. Misidentification of the species was observed in 20% and 5% of the strains with the Vitek Yeast Biochemical Card and API 20C AUX systems, respectively. Amphotericin B demonstrated good in vitro activity (MIC50/90, 0.5 microg/ml) and the MICs for fluconazole were high for all strains (MIC50/90, >64 microg/ml).

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Brazil; Candidiasis; Child; Child, Preschool; Female; Follow-Up Studies; Fungemia; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Rhodotorula; Young Adult

Candida lusitaniae, a Candida species frequently resistant to amphotericin B (AMB), is a rare cause of candidemia. The clinical significance of this in vitro resistant phenotype, the risk factors for, and the clinical presentation of C. lusitaniae fungemia in comparison with those of Candida albicans have not been completely characterized. We reviewed 13 consecutive cases of C. lusitaniae fungemia in cancer patients and compared them with 41 consecutive cases of C. albicans fungemia (1990-2004). The AMB mutational frequency and rate of fungicidal activity was compared between a bloodstream, AMB-susceptible C. lusitaniae isolate associated with clinical failure and reference C. albicans and Candida glabrata strains. In multivariate analysis, patients having C. lusitaniae fungemia were more likely to have neutropenia (p=0.001), stem cell transplantation (p=0.014) and to have received prior antifungals (p=0.04). Mutational frequencies at clinically-achievable AMB exposures were 8 x 10(5) for C. lusitaniae and <1 x 10(9) for C. albicans and C. glabrata reference strains. Compared to C. albicans and C. glabrata, AMB had much less fungicidal activity against C. lusitaniae in time-kill curve analysis. Clinically, C. lusitaniae fungemia was more frequently associated with stem cell transplant and neutropenia. C. lusitaniae, even originally susceptible to AMB, might be less amenable to AMB therapy.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Female; Fungemia; Humans; Male; Middle Aged; Mutation; Neoplasms; Retrospective Studies; Risk Factors; Treatment Outcome

Topics: Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Cunninghamella; Fatal Outcome; Humans; Liposomes; Male; Mucormycosis; Myelodysplastic Syndromes; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole

Effect of antifungal preparation amphotericin B and its lysosomotropic composition with dialdehyde-dextran on functional state of phagocytizing cells in the dynamics of granulomatous inflammation induced by C. albicans was studied on CBA mice. A stimulating effect of amphotericin B on the production of reactive oxygen species by peritoneal and bone marrow phagocytes was observed, while lysosomotropic form of the antibiotic did not stimulate generation of oxygen radicals.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Disease Models, Animal; Mice; Phagocytes; Reactive Oxygen Species

In CBA mice infected with C. albicans, phasic pattern of granulomatosis development was observed. In all groups, the number of granulomas in the liver was minimum on day 56 after infection. Treatment with free amphotericin B and its composition with dialdehyde dextran (CA) reduced the number of infiltrations and granulomas in the liver, the changes were more pronounced in animals receiving CA. A different pattern of cyclic fluctuations of cortisol content in the blood and adrenal glands and progesterone content in the adrenal gland was observed. By the end of observation (day 84), cortisol content in the blood and adrenals of mice treated with CA was considerably lower than in untreated mice and animals receiving amphotericin B.

Topics: Adrenal Cortex Hormones; Adrenal Glands; Amphotericin B; Animals; Anticoagulants; Antifungal Agents; Candidiasis; Dextrans; Drug Therapy, Combination; Granuloma; Hydrocortisone; Liver; Male; Mice; Mice, Inbred CBA; Progesterone

The therapeutic efficacy of a composition of amphotericin B and dialdehyde dextran was much higher than that of amphotericin B in the therapy for systemic candidiasis. This conclusion was derived from the earlier and progressive decrease in the number and size of candidal granulomas in the kidneys. The composition of amphotericin B and dialdehyde dextran was more potent than amphotericin B in decreasing the nephrotoxic effect of C. albicans. The opposite strains of CBA and C57Bl/6 mice differed in morphological signs of granulomatosis in the kidneys, but not in the nephrotoxic effect of C. albicans metabolites.

Topics: Amphotericin B; Animals; Anticoagulants; Antifungal Agents; Candidiasis; Dextrans; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA

A composition of amphotericin B and dialdehyde dextran was used for the therapy of male C57Bl/6 mice with systemic candidiasis. The composition was more effective than free amphotericin B. A decrease in the number and size of candidal granulomas in the lungs was more significant after therapy with the study composition (compared to free amphotericin B).

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Dextrans; Granuloma; Inflammation; Lung Diseases, Fungal; Male; Mice; Mice, Inbred C57BL

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Cardiac Surgical Procedures; Contraindications; Diagnosis, Differential; DNA, Fungal; Echocardiography; Endocarditis; Follow-Up Studies; Humans; Infant; Liposomes; Male; Polymerase Chain Reaction

Epidemiological analysis of nosocomial Candida infections has gained importance due to an increase in these infections during the recent years. This study investigated the prevalence of clinical infections of Candida in anesthesiology intensive care unit patients, and ascertains the level of genetic diversity in the Candida species. A total of 70 Candida isolates, consisting of 42 Candida albicans, 16 Candida glabrata and 12 Candida tropicalis strains isolated from various clinical sites of infection of anesthesiology intensive care unit patients, were analysed. The susceptibility of the isolates against amphotericin B and fluconazole was determined by microdilution method according to Clinical and Laboratory Standards Institute M27-A2 standards. The strains were typed by random amplified polymorphic DNA (RAPD)-PCR using OPE-03, OPE-18, RP4-2 and AP50-1 primers. In the patients with Candida infections, most isolates exhibited different RAPD patterns. Only three C. albicans pairs isolated within a short time period had the same RAPD pattern. Most of the Candida infections in the anesthesiology intensive care unit of our hospital seem to be caused by endogenous strains. Exogenous spread of C. albicans infections occurred less frequently.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cluster Analysis; Cross Infection; DNA Fingerprinting; DNA Primers; DNA, Fungal; Fluconazole; Humans; Intensive Care Units; Microbial Sensitivity Tests; Molecular Epidemiology; Random Amplified Polymorphic DNA Technique

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Drug Resistance, Fungal; Female; Fever; Fungemia; Humans; Immunocompromised Host; Male; Neutropenia

This manuscript reports on two very low birth weight premature infants with respiratory distress, receiving parenteral nutrition and broad-spectrum antibiotics for about 3 weeks, who developed Candida albicans sepsis associated with fungal mycoses and endocarditis, despite treatment with Amphotericin B and Caspofungin. On days 40 and 47, respectively, antifungal therapy was modified to liposomal Amphotericin B combined with Fluconazole 6 mg/kg/day for 4 weeks, resulting in complete resolution of the mycetomas. Our observations suggest that the combination of liposomal Amphotericin B with Fluconazole is able to result in complete resolution of cardiac mycetomas in preterm infants.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Drug Combinations; Endocarditis; Female; Fluconazole; Humans; Infant, Newborn; Infant, Premature; Liposomes; Male; Mycetoma

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Appendicitis; Candidiasis; Female; Fluconazole; Humans; Leukemia, Myeloid, Acute; Liver Diseases; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Splenic Diseases

Amphotericin B poly-aggregates are a new formulation of amphotericin B, which can be obtained cheaply. In this study, we tested the efficacy of this new formulation for treating a disseminated infection by Candida glabrata in a murine model.. Mice were rendered neutropenic by intraperitoneal cyclophosphamide and intravenous 5-fluorouracil administration and infected intravenously with 2 x 10(8) cfu of C. glabrata. The efficacy of the new formulation of amphotericin B was evaluated by survival and tissue burden studies. The experiments were repeated using three different clinical strains of C. glabrata.. Amphotericin B poly-aggregates showed an efficacy similar to that of amphotericin B deoxycholate and liposomal amphotericin B in the treatment of a disseminated murine infection by C. glabrata.

Topics: Amphotericin B; Animals; Candida glabrata; Candidiasis; Chemistry, Pharmaceutical; Colony Count, Microbial; Injections, Intravenous; Kidney; Male; Mice; Spleen; Survival Analysis

The purpose of this investigation is the study of toxicity, in vivo distribution and therapeutic activity against candidiasis of poly-aggregated amphotericin B, in two different formulations: not microencapsulated (P-AMB) or incorporated in albumin microspheres (MP-AMB).. The therapeutic efficacy and toxicity of amphotericin B formulations was studied in an immunocompetent murine model of systemic candidiasis. A pharmacokinetic study was also performed to measure the plasma, kidney, liver and spleen amphotericin B concentrations after administration of the three formulations to mice.. The acute toxicity of P-AMB in mice is lower than that of the conventional amphotericin B reference formulation (D-AMB). The 50% lethal doses were increased at least eight times. Intravenous bolus administration of doses up to 40 mg/kg of body weight of poly-aggregated amphotericin B, either P-AMB or MP-AMB, did not produce acute symptoms of toxicity. Interestingly, in the pharmacokinetic study, significant (P < 0.05) lower plasma and kidney amphotericin B concentrations and higher liver and spleen amphotericin B concentrations were achieved after poly-aggregated amphotericin B formulation (P-AMB and MP-AMB) administration in relation to the reference formulation (D-AMB). At high amphotericin B doses, no significant differences in efficacy (P > 0.05) were observed among the formulations (D-AMB, P-AMB and MP-AMB).. Although the efficacy in the candidiasis treatment was decreased as a consequence of amphotericin B aggregation, it can be compensated by the possibility of increasing the doses with lower nephrotoxicity. Moreover, due to its lower toxicity while maintaining its effectiveness, the poly-aggregated formulations (P-AMB and MP-AMB) have a better therapeutic index than the conventional formulation (D-AMB).

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Dosage Forms; Dose-Response Relationship, Drug; Hot Temperature; Kidney; Liver; Mice; Mice, Inbred ICR; Spleen; Tissue Distribution

Susceptibilities to amphotericin B and fluconazole of 964 Candida isolates collected in Taiwan Surveillance of Antimicrobial Resistance of Yeasts in 2006 were determined. There were 419 (43.5%) Candida albicans, 246 (25.5%) Candida tropicalis, 211 (21.9%) Candida glabrata, 62 (6.4%) Candida parapsilosis, 14 (1.5%) Candida krusei, and 12 (1.2%) others. Interestingly, 16 of the 17 amphotericin B-resistant isolates were non-albicans Candida species. The resistant rate to amphotericin B has decreased from 2.5% in 2002 to 1.8% in 2006. On the other hand, there were 132 C. tropicalis, 14 C. krusei, 10 C. albicans, and 9 C. glabrata isolates that had MICs to fluconazole > or =64 microg/mL. The prevalence of isolates with such high MICs was significantly higher than that in 2002 (17.1% versus 1.9%). Our results further indicate that most of the isolates with MICs to fluconazole > or =64 microg/mL exhibited the "trailing" phenomenon.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Fluconazole; Humans; Microbial Sensitivity Tests; Taiwan

Fungal necrotizing otitis externa is rare, although its frequency has increased over the last few years. We report four cases, which to our knowledge make up the largest series published and discuss the main diagnostic problems and the management of this infection.. Our study investigated two men and two women, all diabetics, aged between 69 and 74 years. All four patients were first treated for bacterial necrotizing otitis externa. Diagnosis was reviewed after a lack of response to antibiotic therapy. Aspergillus flavus and Candida parapsilosis were the fungal agents isolated in each of the two patients. Diagnosis was established based on the pathological specimen for one patient. The last patient was treated without identifying the causal fungus. Two patients developed facial paralysis during disease progression. Treatment was based on intravenous amphotericin B and oral itraconazole. Three patients are now free of disease after a three- to six-month course of antifungal therapy; one patient was not followed up.. Fungal necrotizing otitis externa should be suspected in cases where there is no response to antipseudomonal antibiotic therapy. Deep biopsies from the external auditory canal or the mastoid are usually needed to confirm the diagnosis.

Topics: Aged; Amphotericin B; Antifungal Agents; Candidiasis; Female; Fluconazole; Humans; Male; Necrosis; Otitis Externa; Tomography, X-Ray Computed

Candida guilliermondii (C. guilliermondii) are uncommon, representing approximately 1% of all Candida infections, but have been reported to show a higher rate of drug-resistance and mortality rate than C. albicans. Current guidelines for treatment of non-albicans candidemia in neutropenic patients now recommend the use of amphotericin B or voriconazole (VRCZ). We describe here the successful treatment for a 58-year-old male with azole-refractory C. guilliermondii fungemia by combination with liposomal (L-AmB) and micafungin (MCFG) therapy. He was diagnosed as having mantle cell lymphoma, and treatment with HyperCVAD (Rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) was started. Despite prophylactic treatment with fluconazole, he developed fungemia due to C. guilliermondii 41 days after the start of chemotherapy. Positive blood culture and high levels of (1-->3)-beta-D-glucan persisted despite changing the treatment from fluconazole to voriconazole. Although L-AmB was also added to VRCZ, the clinical symptoms worsened. When MCFG was combined with L-AmB, the symptoms and data dramatically improved. Thus, combination therapy consisting of MCFG and L-AmB might be more effective against candidemia that is refractory to azole than combination therapy with VRCZ and L-AmB.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Azoles; Candidiasis; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Resistance, Fungal; Drug Therapy, Combination; Echinocandins; Fungemia; Humans; Immunocompromised Host; Lipopeptides; Lipoproteins; Lymphoma, Mantle-Cell; Male; Micafungin; Middle Aged; Treatment Outcome; Vincristine

Invasive fungal infection is one of the major causes of morbidity and mortality in immunocompromised patients. The occurrence of two invasive fungal infections in one patient at the same time is quite rare. Here the authors report on two adolescent patients with acute lymphoblastic leukemia who developed combined invasive pulmonary aspergillosis and hepatosplenic candidiasis during chemotherapy. They were treated with liposomal amphotericin B, but one of them died due to massive pulmonary hemorrhage during recovery from neutropenia.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Fatal Outcome; Humans; Immunocompromised Host; Liver Diseases; Lung Diseases, Fungal; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiography; Splenic Diseases; Typhlitis

Randomized controlled trials suggest that prophylactic administration of antifungal agents reduce the rate of colonization and invasive Candida infection in a subgroup of high-risk very low birth weight (VLBW) neonates. The extent of antifungal prophylaxis use in the United Kingdom and Ireland is unknown.. A postal questionnaire was administered to neonatologists practicing in the United Kingdom and Ireland caring for VLBW infants. Information was requested on the prophylactic agents used, dosing schedules and duration of therapy. The rationale for reported practices was also ascertained.. The response rate was 55% (125/228). Antifungal prophylaxis use was reported by 66 (53%) respondents. First-line agents utilized included oral nystatin (53%) and intravenous fluconazole (41%). The most frequent indications for antifungal prophylaxis included antibiotic administration in 45 (68%) and decreased birth weight in 33 (50%) respondents. The majority of respondents who did not use antifungal prophylaxis felt that the perceived rate of invasive fungal disease within their unit was not high enough to justify its use.. A small majority of clinicians caring for VLBW neonates routinely use antifungal prophylaxis. This reflects the wide variation in the incidence of invasive disease, lack of guidelines supporting a role for prophylaxis and concerns related to emergence of resistant strains.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Fluconazole; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Very Low Birth Weight; Nystatin; Practice Patterns, Physicians'

Here we report on two isolates of Candida glabrata recovered from urine samples collected from of an Intensive Care Unit patient. D1/D2 and ITS 1+2 rDNA sequence analysis confirmed its identification. The isolates were cholesterol dependent and resistant to Amphotericin B.

Topics: Amphotericin B; Candida; Candida glabrata; Candidiasis; Cholesterol; DNA, Fungal; DNA, Ribosomal Spacer; Drug Resistance, Fungal; Female; Humans; Intensive Care Units; Middle Aged; Urine

The objective of the current retrospective study was to compare the epidemiology of candidemia and its risk factors in patients who had hematologic malignancies(HM) with those in patients who had solid tumors (ST).. The medical and electronic records of all patients with cancer who had candidemia at the authors' institution from 1993 to 2003 were reviewed for demographic data and clinical information, including the use of prophylactic fluconazole, the infecting Candida species, and the source of candidemia (catheter-related vs other apparent sources).. Six hundred thirty-five patients with candidemia were analyzed. C. glabrata and C. krusei were the leading causes of candidemia in 31% and 24% of patients with HM, respectively, and in 18% and 2% of patients with ST, respectively (P < .001). A catheter was the source of candidemia in 36% of the patients with ST and in 12% of the patients with HM (P < .001). Response to antifungal therapy occurred in 73% of the ST group compared with 49% of the HM group (P < .001). Multivariate logistic regression analysis revealed that fluconazole prophylaxis was a risk factor for both C. glabrata and C. krusei candidemia. The analysis also identified neutropenia as a risk factor for all candidemia and catheter-related infection as a risk factor for C. parapsilosis candidemia.. The results of this study indicated that C. glabrata and C. krusei were the leading causes of candidemia in patients with HM. Neutropenia was the leading risk factor for all candidemia, whereas the catheter was the leading risk factor for C. parapsilosis candidemia.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Catheterization, Central Venous; Cohort Studies; Drug Resistance, Fungal; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia; Retrospective Studies; Risk Factors

Long-term dialysis in children with multiple handicaps has become easier with the advent of continuous ambulatory peritoneal dialysis (PD). Due to the widespread use of PD and the long survival of patients with spina bifida, an increasing number of patients with spina bifida are on PD. The viability and safety of PD in spina bifida patients with a ventriculoperitoneal shunt (VPS) have been a matter of concern. Some authors consider the presence of a VPS a relative contraindication for PD, but more recent reports suggest that PD under close monitoring is not contraindicated. We report a 17-year-old girl born with meningomyelocele, hydrocephalus and neurogenic bladder who was maintained on VPS. She reached end-stage renal failure 17 years later and was put on PD based on family and patient preference. She had an uneventful course in the initial 9 months, but later developed fungal peritonitis which was successfully managed with catheter withdrawal and an intravenous antifungal agent (amphotercin 0.75 mg/kg). Simultaneous ventricle-aspirated cerebrospinal fluid was sterile. To our knowledge, this is the first report of fungal infection in such a patient. Although we share the view that PD is not an absolute contraindication in patients with a functioning VPS, its likely complications, especially infectious complications in developing countries, should be kept in mind before initiating PD in such patients.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Female; Growth Disorders; Humans; Hydrocephalus; Kidney Failure, Chronic; Meningomyelocele; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Recurrence; Spina Bifida Cystica; Urinary Bladder, Neurogenic; Urinary Catheterization; Urinary Tract Infections; Ventriculoperitoneal Shunt

The aim of this study was to investigate the in vitro interaction of amphotericin B in combination with fluconazole or voriconazole against Candida albicans clinical isolates by using a broth microdilution checkerboard assay and E-test. A total of 30 C. albicans strains isolated from blood, urine, sputum and pus samples were included to the study and the minimum inhibitory concentrations (MICs) of amphotericin B (AMB), fluconazole (FLU) and voriconazole (VOR) were determined by broth microdilution method and E-test. All strains tested for susceptibility were interpreted as susceptible by both methods (FLU MICs < 8 microg/ml, VOR and AMB MICs < 1 microg/ml). The rates of MIC agreement between two methods were as follows: AMB, 83%; FLU, 97%; VOR, 97%. AMB+ FLU and AMB+VOR combinations were tested by checkerboard broth microdilution and E-test methods. The combination test results were determined by using the fractional inhibitory concentration (FIC) index as synergistic, indifferent or antagonistic. AMB+FLU combination tested by checkerboard broth microdilution revealed synergy in one strain (3.3%) and antagonism in none, while the same combination tested by E-test revealed synergy in two (6.6%) and antagonism in four (13.3%) strains. The strains which exhibited synergy were different from eachother in two assays. This combination led to indifferent results in 23 (76.6%) of the strains. On the other hand AMB+VOR combination yielded synergistic results in two (6.6%) strains by both of the methods, however, these two strains were again different from eachother. No antagonism was detected by AMB+VOR combination while the combination was indifferent in 26 (86.6%) of the strains. Agreement between the checkerboard and E-test results was 87%. Although significant synergy was not detected in AMB+azole combinations, it was yet hopeful to obtain no antagonism. However, multi-center, large-scale, well standardized in-vitro and clinical studies about AMB and azole interaction which is a matter of debate, are necessary.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Drug Interactions; Fluconazole; Humans; Microbial Sensitivity Tests; Pyrimidines; Reproducibility of Results; Triazoles; Voriconazole

To investigate if combination therapy with liposomal amphotericin B (LAmB), and caspofungin (CAS) is superior to monotherapies in an experimental model with azole-resistant Candida albicans.. This study was carried out between October 2006 and August 2007 in Celal Bayar University, Manisa, Turkey. A total of 144 mice were included in the study, and divided into 4 groups as: control (n=36), CAS treatment group n=36, LAmB treatment group (n=36), and combination therapy group (n=36). Treatment efficacy was assessed by determining survival, as well as, the decrease in tissue fungal densities.. The fungal densities in tissues were significantly reduced, and the survival rates were prolonged with either CAS only, or LAmB only, or with combination therapy compared to those of controls (p<0.05). There was no significant difference between monotherapy groups. Decrease in tissue fungal densities were significant in CAS and LAmB (1mg/kg) combination group, compared to CAS (1mg/kg) and LAmB (1mg/kg) groups (p=0.004 for CAS, p=0.009 for LAmB). Survival rates were similar in both treatment groups.. The combination treatment was superior with 1mg/kg of doses of LAmB and CAS in terms of reducing the tissue fungal burden. Although with combination therapy the survival rates prolonged in all subgroups, no significant difference between the combination and monotherapies could be shown. Additional studies with a large number of cases are warranted to investigate the superiority of combination therapy.

Topics: Amphotericin B; Animals; Candidiasis; Caspofungin; Drug Therapy, Combination; Echinocandins; Lipopeptides; Mice; Statistics, Nonparametric; Survival Rate

This study analyzed the correlation between the results obtained through two microdilution methods: Clinical and Laboratory Standard Institute (CLSI) (M27-A2) and European Committee on Antibiotic Susceptibility Testing (EUCAST) (document E. Dis. 7.1) and an agar base method Etest for determining minimmun inhibitory concentration (MIC) for amphotericin B and fluconazole against 30 clinical isolates of Candida spp. The agreement between Etest, CLSI and EUCAST MICs within +/- 2 log2 dilutions was higher for amphotericin B than for fluconazole However, Pearson correlation demonstrated a greater agreement for fluconazole. The categorical agreement between MICs provided by the Etest/ CLSI and Etest/EUCAST methodologies was high for both amphotericin B (100%) and fluconazole (> or = 96.66%). This study demonstrated the adequacy of Etest method using Mueller Hinton agar to evaluate amphotericin B and fluconazole susceptibility of clinical isolates of Candida spp.

Topics: Agar; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Culture Media; Diffusion; Fluconazole; Microbial Sensitivity Tests

Candida parapsilosis is an extremely rare cause of meningitis. We report the case of a neonate born at 26+4 weeks of gestation who was admitted to the neonatal intensive care unit at our institution due to respiratory immaturity. During the course of a 3-month hospitalization, the neonate developed fever and lethargy. A lumbar puncture revealed milky-white, turbid cerebrospinal fluid which contained many nucleated cells, mostly neutrophils. Microscopic examination of the cerebrospinal fluid revealed marked acute inflammation and fungal yeast forms, and cultures of the cerebrospinal fluid and peripheral blood yielded C. parapsilosis. Imaging studies subsequently revealed a subdural empyema related to epidural migration of a central venous catheter (CVL). The neonate received extended therapy with amphotericin B and fluconazole. He responded favorably to therapy and was discharged 3 months after birth. This case underscores the clinical importance of the recognition and treatment of a potentially lethal fungal pathogen of the central nervous system and the need for awareness of complications resulting from CVL malposition.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Catheterization, Central Venous; Empyema; Epidural Space; Fluconazole; Foreign-Body Migration; Humans; Infant, Newborn; Male; Meningitis, Fungal; Radiography

To investigate the economic impact of micafungin (MICA) for treatment of invasive candidiasis and candidaemia (systemic Candida infections), a health economic analysis was conducted comparing MICA with liposomal amphotericin B (L-AMB).. The model was based on a phase III, randomised, double-blind, clinical trial which compared MICA with L-AMB. The model entailed a period of 14-20 weeks starting from initiation of treatment and was analysed from a German hospital perspective.. The main outcome measures were defined as the percentage of patients achieving clinical and mycological response after initial treatment and who were alive at the end of the study (EOS), and the total treatment-associated costs over the study period.. The health economic analysis shows that with MICA, 52.9% of patients are successfully treated and were alive at EOS compared to 49.1% for L-AMB. In addition, MICA has, on average, lower treatment-associated costs than L-AMB with euro43 243 and euro49 216 per patient, respectively. Because the costs are lower and the effectiveness is higher for MICA in comparison with L-AMB, MICA is more cost-effective than L-AMB. However, the results of the probabilistic sensitivity analysis show that the differences cannot be considered significant due to a large variance, although MICA remained the most cost-effective option throughout the one-way sensitivity analyses.. The lower costs and higher effectiveness reported for MICA versus L-AMB in this analysis indicate that MICA may be a more cost-effective therapy in the treatment of invasive candidiasis and candidaemia when compared with L-AMB.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cost-Benefit Analysis; Double-Blind Method; Echinocandins; Germany; Humans; Lipopeptides; Lipoproteins; Micafungin; Models, Economic; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic

Little information is available about the molecular mechanisms responsible for polyene resistance in pathogenic yeasts. A clinical isolate of Candida glabrata with a poor susceptibility to polyenes, as determined by disk diffusion method and confirmed by determination of MIC, was recovered from a patient treated with amphotericin B. Quantitative analysis of sterols revealed a lack of ergosterol and an accumulation of late sterol intermediates, suggesting a defect in the final steps of the ergosterol pathway. Sequencing of CgERG11, CgERG6, CgERG5, and CgERG4 genes revealed exclusively a unique missense mutation in CgERG6 leading to the substitution of a cysteine by a phenylalanine in the corresponding protein. In addition, real-time reverse transcription-PCR demonstrated an overexpression of genes encoding enzymes involved in late steps of the ergosterol pathway. Moreover, this isolate exhibited a pseudohyphal growth whatever the culture medium used, and ultrastructural changes of the cell wall of blastoconidia were seen consisting in a thinner inner layer. Cell wall alterations were also suggested by the higher susceptibility of growing cells to Calcofluor white. Additionally, complementation of this isolate with a wild-type copy of the CgERG6 gene restored susceptibility to polyenes and a classical morphology. Together, these results demonstrated that mutation in the CgERG6 gene may lead to a reduced susceptibility to polyenes and to a pseudohyphal growth due to the subsequent changes in sterol content of the plasma membrane.

Topics: Antifungal Agents; Candida glabrata; Candidiasis; DNA Primers; Genes, Fungal; Genetic Complementation Test; Methyltransferases; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation, Missense; Phenotype; Polyenes; Reverse Transcriptase Polymerase Chain Reaction; RNA, Fungal; RNA, Messenger; Sterols

Candida parapsilosis has emerged as an important nosocomial pathogen. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of caspofungin (CAS) in combination with amphotericin B (AMB) against three clinical isolates of C. parapsilosis. Although there was a significant reduction of the MIC of one or both drugs used in combination, an indifferent interaction (fractional inhibitory concentration index greater than 0.50 and less than or equal to 4.0) was observed in 100% of cases. This finding was confirmed by killing curve studies. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were often significantly greater than those produced by each drug alone. Antagonism was never observed. In a murine model of systemic candidiasis, CAS at either 0.25 or 1 mg/kg/day combined with AMB at 1 mg/kg/day was significantly more effective than each single drug at reducing the colony counts in kidneys. Higher doses of the echinocandin (i.e., 5 and 10 mg/kg/day) combined with the polyene did not show any advantage over CAS alone. Overall, our study showed a positive interaction of CAS and AMB against C. parapsilosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candidiasis; Caspofungin; Colony Count, Microbial; Drug Combinations; Echinocandins; Kidney; Lipopeptides; Male; Mice; Microbial Sensitivity Tests; Peptides, Cyclic

Amphotericin B and flucytosine (5FC) have an additive effect when used for disseminated candidiasis. Here, we bridge the results of an experimental pharmacodynamic study to humans and demonstrate that a 5FC dosage of 25 mg/kg of body weight/day in four divided doses in combination with amphotericin B produces near-maximal effect.

Topics: Algorithms; Amphotericin B; Antifungal Agents; Area Under Curve; Candidiasis; Child; Drug Interactions; Flucytosine; Humans; Models, Statistical; Monte Carlo Method

Novel 2-aminotetralin derivatives were synthesized as antifungal agents. The 2-aminotetralin scaffold was chemically designed to mimic the tetrahydroisoquinoline ring of the lead molecule described before. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 10a, 12a, 12c, 13b, and 13d are more potent than fluconazole against seven testing human fungal pathogens. Compound 10b exhibits much higher antifungal activities against all of the four fluconazole-resistant clinic Candida albicans strains than the control drugs including amphotericin B, terbinafine, ketoconazole, and itraconazole. The mode of action of some compounds to the potential receptor lanosterol 14alpha-demethylase (CYP51) was investigated by molecular docking. The studies presented here provide a new structural type for the development of novel antifungal compounds. Furthermore, 10b was evaluated in vivo by a rat vaginal candidiasis model, and it was found that 10b significantly decreases the number of fungal colony counts.

Topics: Administration, Intravaginal; Animals; Antifungal Agents; Binding Sites; Candida albicans; Candidiasis; Cytochrome P-450 Enzyme System; Drug Resistance, Fungal; Female; Fluconazole; Microbial Sensitivity Tests; Models, Molecular; Oxidoreductases; Protein Binding; Rats; Sterol 14-Demethylase; Structure-Activity Relationship; Tetrahydronaphthalenes; Vaginal Diseases

Disseminated candidiasis is associated with a high rate of morbidity and mortality. The presence of neutrophils and the timely administration of antifungal agents are likely to be critical factors for a favorable therapeutic outcome of this syndrome. The effect of neutropenia on the temporal profile of the burden of Candida albicans in untreated mice and those treated with amphotericin B was determined using a pharmacodynamic model of disseminated candidiasis. A mathematical model was developed to describe the rate and extent of the C. albicans killing attributable to neutrophils and to amphotericin B. The consequences of a delay in the administration of amphotericin B, flucytosine, or micafungin were studied by defining dose-response relationships. Neutrophils caused a logarithmic decline in fungal burden in treated and untreated mice. The combination of amphotericin B and neutrophils resulted in a high rate of Candida killing and a sustained anti-C. albicans effect. In neutropenic mice, 5 mg/kg of body weight of amphotericin B was required to prevent progressive logarithmic growth. An increased delay in drug administration resulted in a reduction in the maximum effect to a point at which no drug effect could be observed. Neutrophils and the timely initiation of antifungal agents are critical determinants in the treatment of experimental disseminated candidiasis.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Disease Models, Animal; Dose-Response Relationship, Drug; Echinocandins; Flucytosine; Kidney; Lipopeptides; Lipoproteins; Male; Micafungin; Mice; Microbial Sensitivity Tests; Neutropenia; Neutrophils; Peptides, Cyclic; Time Factors

Although exposure of Candida albicans cells to high-dose (4 mM) methylprednisolone stimulated microbial growth, germination rate in serum and phospholipase release, it also promoted the recognition of C. albicans cells by polymorphonuclear leukocytes. Pretreatment of C. albicans cells with methylprednisolone did not result in any increase in the pathogenicity of the fungus in intraperitoneal and intravenous mouse assays. Therefore, the virulence of C. albicans is unlikely to increase in patients treated with comparably high-dose methylprednisolone on skin and mucosal membranes. Methylprednisolone treatments also increased the production of conjugated dienes and thiobarbituric acid-reactive substances, and the menadione sensitivity of C. albicans cells, which can be explained by a significant decrease in the specific activities of several antioxidant enzymes. The combination of methylprednisolone with oxidants, e.g. in topical applications, may be of clinical importance when the predisposition to candidiasis is high. Methylprednisolone treatments negatively affected membrane fluidity and decreased the antifungal effects of both the polyene antibiotic nystatin and the ergosterol biosynthesis inhibitor lovastatin, and also enhanced the deleterious effects of the polyene antimycotic amphotericin B on C. albicans cells. These corticosteroid-polyene drug interactions should be considered in the treatment of C. albicans infections in patients with prolonged topical application of corticosteroids.

Topics: Amphotericin B; Animals; Antifungal Agents; Antioxidants; Candida albicans; Candidiasis; Cell Membrane Permeability; Drug Interactions; Female; Glucocorticoids; Lipid Peroxidation; Methylprednisolone; Mice; Microbial Sensitivity Tests; Oxidative Stress; Virulence; Vitamin K 3; Vitamins

In this work, we collect data from surveys of bloodstream Candida isolates performed in Brazil from 1996 to 2004. Besides, we analyzed the species distribution of bloodstream Candida isolates together with potential risk factors for candidemia and the susceptibility profile of these isolates in patients from Hospital das Clínicas in Goiânia city, Brazil. Blood samples were collected in the admission day and on every 7 days, in the intensive care unit (ICU) of a tertiary hospital. Candida isolates were identified by standard protocols that included germ tube formation, chlamydoconidia production on cornmeal agar and sugar fermentation and assimilation tests. Data of patients were recorded and analyzed according to age at the time of diagnosis, gender and presence of potential risk factors. Statistical analysis was used to determine if the time of hospital permanence increased Candida colonization in ICU patients' blood. The antifungal susceptibility testing was performed by broth microdilution method according to document NCCLS/CLSI M27-A2. Among the 345 blood samples cultured, candidemia was recovered in 33 patients, which were isolated 51.5% of Candida non-albicans. Fungemia was associated with long-term hospitalization. Fluconazole, itraconzole, voriconazole and amphotericin B exhibited a potent activity against all isolates of Candida. Voriconazole MICs were much low for all isolates tested. This work confirms data of increase of Candida non-albicans species in bloodstream in ICU and shows that voriconazole in vitro activity was higher than those of itraconazole, fluconazole and amphotericin B.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Brazil; Candida; Candidiasis; Drug Resistance, Fungal; Female; Fluconazole; Hospitals; Humans; Intensive Care Units; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Pyrimidines; Risk Factors; Triazoles; Voriconazole

To evaluate the efficacy of newly developed antifungal agents caspofungin and voriconazole in Candida albicans endophthalmitis in rabbit eyes.. Thirty New Zealand white rabbits were divided into four treatment groups and one control group. One eye of each rabbit was infected by inoculation of 1 x 10(4) CFU/ml of C. albicans. Seventy-two hours after the inoculation, caspofungin 100 microg/0.1 ml in group 1 (n = 6), voriconazole 50 microg/0.1 ml in group 2 (n = 6), amphotericin B 10 microg/0.1 ml in group 3 (n = 6), itraconazole 10 microg/0.1 ml in group 4 (n = 6), and 0.1 ml NaCl 0.9% in control group (n = 6) were injected into the vitreous cavity. Clinical and histopathologic examination scores and microbiological analysis of vitreous aspirates were compared.. There was statistically significant difference in the clinical scores, histopathologic scores, and mean CFU/ml between the treatment and control groups (p < 0.05). In caspofungin and voriconazole groups, histopathologic scores and mean CFU were lower than other treatment groups and control group.. Intravitreal injection of caspofungin and voriconazole was effective against C. albicans endophthalmitis in this experimental rabbit model.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Caspofungin; Colony Count, Microbial; Cornea; Disease Models, Animal; Echinocandins; Endophthalmitis; Eye Infections, Fungal; Itraconazole; Lipopeptides; Peptides, Cyclic; Pyrimidines; Rabbits; Triazoles; Voriconazole

The evolution of the incidence and the epidemiology of ocular candidiasis in our hospital during the past 12 y, as well as the factors associated with poor functional outcome were analysed. A retrospective study of all cases of ocular candidiasis admitted to a university hospital between 1993 and 2004 was performed. Epidemiological, clinical and final outcome data were recorded. 37 episodes of ocular candidiasis in 36 patients were studied. 28 (75%) episodes occurred between 1993 and 1998 (13.09 episodes/100,000 admissions/y), and all of these patients were intravenous drug users. In contrast, only 9 episodes of ocular candidiasis were recorded between 1999 and 2004 (4.42 episodes/100,000 admissions/y; p<.0001) and 3 (33%) patients were not drug users (p<0.01). 19 (57%) cases had final visual acuity <0.1. Treatment with conventional amphotericin B instead of other newer antifungal drugs was associated with poor visual prognosis in the univariate (p = 0.03) and multivariate (p = 0.03) analysis. In conclusion, the incidence of ocular candidiasis has decreased significantly in recent y and the epidemiology has changed. Currently, one-third of patients are immunocompromised non-drug users. Therapy with conventional amphotericin B instead of newer antifungal drugs appears to be associated with a poorer functional outcome.

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Eye Infections, Fungal; Female; Fluconazole; Humans; Incidence; Male; Prognosis; Retrospective Studies; Spain; Substance Abuse, Intravenous; Treatment Outcome; Visual Acuity

To study the relation between serum and peritoneal levels of amphotericin B and flucytosine during intravenous treatment in patients with abdominal sepsis due to a perforated gut.. Included were consecutive patients with abdominal sepsis due to a perforated gut, who were treated intravenously with amphotericin B and/or flucytosine after surgery if an abdominal drain was present. Amphotericin B and flucytosine were measured from simultaneously collected serum and abdominal fluid samples.. Twenty-one consecutive patients were included. Five repeated samples were taken from three patients. The time interval between the start of the medication and the first sampling was median 4.0 days (range 2-7 days). The correlation coefficient (r(2)) between serum and peritoneal levels of amphotericin B was 0.79. In nine patients (43%) with a maximum serum level of 0.28 mg/L, amphotericin B in the peritoneal fluid was undetectable. The lowest serum level that was present with a detectable peritoneal level was 0.16 mg/L. A short duration of treatment (2 days) was associated with low serum and undetectable peritoneal levels. In seven patients, flucytosine levels were measured. Peritoneal flucytosine levels did not differ significantly from serum levels. Serum and peritoneal flucytosine levels correlated well with r(2)=0.88. Peritoneal amphotericin B level was inversely correlated with C-reactive protein level on the same day (r(2)=0.30).. It is shown, during continuous infusion, that peritoneal levels of amphotericin B are lower than serum levels. The amphotericin B serum levels should exceed 0.5 mg/L to obtain peritoneal levels above MIC values. Flucytosine levels in the abdominal fluid are comparable to serum levels and within MIC ranges.

Topics: Aged; Amphotericin B; Ascitic Fluid; Candidiasis; Critical Care; Female; Flucytosine; Fungemia; Humans; Male; Middle Aged; Peritonitis; Prospective Studies

We hypothesized that effective prophylactic treatment of fungal infections would require adequate drug penetration and retention at potential infection sites. Using a mouse model, we examined liposomal amphotericin B (L-AmB) biodistribution, cell localization and retention in kidneys, lungs, liver and spleen to evaluate effective dosing regimens for prophylaxis of Candida glabrata and Candida albicans infections.. Following treatment of mice with cumulative doses of L-AmB (60-225 mg/kg), a bioassay was done to determine tissue drug concentrations 12 h to 6 weeks post-treatment. Immunohistochemical staining with anti-amphotericin B antibodies was used for cellular drug localization. Mice were treated prophylactically with 15-90 mg/kg L-AmB and challenged intravenously 1-7 days later with C. glabrata or they were given a total of 60 mg/kg as daily or intermittent dosing followed by intravenous challenge with C. albicans 3 or 6 weeks later.. On the basis of microg/g tissue, the relative amount of drug was in the order spleen > liver > kidneys > lungs. Amphotericin B levels were maintained above the MIC for many fungi for 1 week in lungs and for as long as 6 weeks in kidneys and spleen. Drug localized in kidney tubular epithelial cells and in macrophages of liver and spleen. In prophylactic models, fungal burden was reduced by several 1000-fold or was undetectable within target tissues (kidneys, spleen).. These observations underscore the importance of including drug tissue levels to obtain a better understanding of L-AmB efficacy. The sustained concentrations of bioactive AmB in many tissues provide a further rationale for investigating L-AmB prophylactic regimens.

Topics: Amphotericin B; Animals; Antibiotic Prophylaxis; Antifungal Agents; Candida albicans; Candida glabrata; Candidiasis; Female; Kidney; Liposomes; Mice; Mice, Inbred DBA; Spleen

The first outbreak of Candida haemulonii fungemia is described. The seven isolates from the blood of four neonates were identified by DNA sequencing of the ribosomal DNA. They were all resistant to amphotericin B, fluconazole, and itraconazole. This report highlights the emergence of C. haemulonii as an opportunistic pathogen in immunocompromised patients.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Disease Outbreaks; Drug Resistance, Fungal; Female; Fluconazole; Fungemia; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Itraconazole; Male; Microbial Sensitivity Tests; Molecular Sequence Data; Sequence Analysis, DNA

A 74-y-old male receiving haemodialysis presented with right-sided otalgia, otorrhoea and diffuse swelling on the right external auditory canal. Following an initial successful treatment with prolonged intravenous antibiotics, the patient relapsed with a secondary infection in the same site due to Candida glabrata. We report an unusual case of malignant otitis externa caused by the fungus C. glabrata.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Fluconazole; Gallium Radioisotopes; Humans; Male; Otitis Externa; Radiography; Recurrence; Renal Dialysis; Tomography, Emission-Computed, Single-Photon

In recent years, the incidence of systemic infections due to Candida increased, but the incidence of spondylodiscitis remained low, and epidural involvement during such infection was seldom reported. The purpose of this study was to report the cases of 2 young male heroin addicts who developed spondylodiscitis due to Candida sp., with epidural involvement. In one case, a microbiological diagnosis was obtained after biopsy. In the other case, the diagnosis was based on serological data and Candida antigenemia. In both cases, an oral fluconazole based therapy was administered at first (because of a poor peripheral venous system), but proved to be inefficient. A secondary therapy by liposomal amphotericin B proved efficient allowing a favourable evolution. This pathology raised a number of problems concerning diagnosis and treatment. The clinical data was non-specific the paraclinical diagnosis required MRI, and biopsy. When microbiological assessment is negative, serology and the antigenemia can be useful. The treatment pattern suggested for the management of bone and joint infections is: intravenous amphotericine B for 2-3 weeks, followed by oral administration of fluconazole or voriconazole for 6-12 month. Surgical treatment is recommended only to patients ay risk of neurological disorders or severe epidural abscess.

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Discitis; Fluconazole; Humans; Magnetic Resonance Imaging; Male; Spine

A patient with Candida albicans thrush and oesophagitis was treated with high doses of caspofungin but treatment eventually failed. Four C. albicans isolates were serially recovered before and after caspofungin treatment. A microbiological study was performed to characterize these four isolates.. In vitro antifungal susceptibility testing was performed by the EUCAST reference method in RPMI and AM3 and by Etest. Molecular typing of the four isolates was done by sizing three polymorphic microsatellite markers. To look for specific mutations, sequencing of a region of the gene encoding the 1-3-beta-D-glucan synthase was performed for the four isolates.. In vitro antifungal susceptibility testing showed an increase in both caspofungin and micafungin MICs for the two isolates recovered after caspofungin treatment failure. The best discrimination between the pre-treatment and post-treatment isolates was obtained with Etest. Molecular typing of the four isolates showed that the post-treatment isolates with reduced susceptibility were identical to a susceptible pre-treatment isolate, suggesting the acquisition of caspofungin resistance. Sequencing of the gene encoding the 1-3-beta-D-glucan synthase showed a mutation responsible for an amino acid change at Phe-641 that could confer reduced susceptibility to both echinocandins.. Our results indicate that is it useful to perform in vitro susceptibility testing in the cases of clinical failure during caspofungin therapy.

Topics: Adult; Amino Acid Sequence; Amino Acid Substitution; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Caspofungin; Drug Resistance, Fungal; Echinocandins; Fluconazole; Genotype; HIV Infections; HIV-1; Humans; Lipopeptides; Lipoproteins; Male; Micafungin; Microbial Sensitivity Tests; Molecular Sequence Data; Peptides, Cyclic; Pyrimidines; Treatment Failure; Triazoles; Voriconazole

To characterize the clinical features and therapeutic outcome of Candida keratitis.. Retrospective, observational case series.. We reviewed 26 patients treated for Candida keratitis, including two with recurrent keratitis and one with bilateral infection.. Of 29 keratitis episodes resulting from Candida albicans (n = 20) or Candida parapsilosis (n = 9), 16 (55%) complicated chronic ocular surface disease, and nine (31%) followed previous keratoplasty. Only two were clinically suspected to have keratomycosis at initial presentation, and 21 (72%) used antibacterial therapy before corneal scrapings. Reconstructive keratoplasty occurred more often in previously grafted eyes (P = .03). Visual outcome was 20/60 or better in six (100%) medically treated eyes with good presenting visual acuity but in only five eyes (24%) with worse initial vision (P = .002).. Candida keratitis is an opportunistic infection of a compromised cornea that often is misdiagnosed initially and, despite antifungal therapy, occasionally requires corneal grafting.

Topics: Administration, Topical; Amphotericin B; Antifungal Agents; Candidiasis; Corneal Transplantation; Corneal Ulcer; Eye Infections, Fungal; Female; Humans; Male; Middle Aged; Recurrence; Retrospective Studies; Risk Factors; Treatment Outcome; Visual Acuity

Topics: Adult; Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Endocarditis; Female; Heart Valve Diseases; Humans; Infusions, Intravenous; Nephrotic Syndrome; Tricuspid Valve

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Candidiasis; Cryptococcosis; Drug Combinations; Fungemia; Humans; Phosphatidylcholines; Phosphatidylglycerols; Viscera

We report one case of severe Candida glabrata chorioamnionitis and septicemy occurring in a twin pregnancies achieved by in vitro fertilization techniques which resulted in pregnancy loss after preterm rupture of the membrane at 22 weeks of gestation despite a treatment with amphotericin B.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Candida glabrata; Candidiasis; Chorioamnionitis; Female; Fertilization in Vitro; Fetal Death; Fetal Membranes, Premature Rupture; Humans; Pregnancy; Pregnancy, Multiple; Sepsis; Twins

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Biofilms; Candidiasis; Catheterization; Erythromycin; Female; Humans; Short Bowel Syndrome; Staphylococcal Infections

In recent years, the incidence of Candida albicans infections tends to decrease, at least in some centers other Candida species have emerged as opportunistic pathogens. Among non-albicans Candida species, C. glabrata is one of the most frequently isolated species. In this study, the in vitro activities of amphotericin B, itraconazole and fluconazole were tested against 134 clinical C. glabrata strains. The isolation and identification of the isolates were done by standard mycological methods. Microbroth susceptibility tests were done in accordance with CLSI microdilution method (M27A-2). MICs were read at both 24 and 48 hours. At 24 h, MIC range, MIC50 and MIC90 values for amphotericin B were 0.5-4 micorg/ml, 2 microg/ml and 4 microg/ml, respectively. At 48 h, MIC range, MIC50 and MIC90 values for amphotericin B were 2-4 microg/ml, 4 microg/ml and 4 microg/ml respectively. At 24 h, 97% of the isolates were susceptible (S) and 3% were dose-dependent susceptible (S-DD) to fluconazole. None of the isolates were resistant (R) to fluconazole at this time point. At 48 h, 94% of the isolates were S, 5.2% were S-DD and 0.8% were R to fluconazole. At 24 h, 20.9% of the isolates were S, 73.1% were S-DD and 6% were R to itraconazole. At 48 h, 0.8% of the isolates were S, 62.7% were S-DD and 36.5% were R to itraconazole. These results suggest that although C.glabrata strains that were isolated in our hospital were rarely resistant to fluconazole, resistance rate to itraconazole is relatively high. Most of the isolates that are resistant to itraconazole remain susceptible to fluconazole.

Topics: Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Fluconazole; Humans; Itraconazole; Microbial Sensitivity Tests

Biofilm producing Candida species are known to be more resistant to immune response and antimicrobial agents which leads to treatment failure. The aim of this study was to investigate the biofilm production among Candida species that were isolated from hospitalized patients and to compare the in vitro activities of antifungal agents with biofilm production. A total of 116 Candida spp. (79 C. albicans and 37 non-albicans Candida spp.) isolated from various specimens (blood, sterile body fluids, mucosal and skin lesion samples) were included to the study. Fluconazole, itraconazole, amphotericin B and caspofungin susceptibilities of the isolates were determined by broth microdilution method according to CLSI M27-A2 standards. Biofilm production of Candida spp. was determined by microplate method, using brain heart infusion broth supplemented with 0.25% glucose as a growth medium. Biofilm formation was detected in 33 of 116 isolates (28%) and 11 of them (33%) were the strains isolated from hemocultures. Biofilm production was determined more commonly in blood isolates than the strains isolated from other samples (p < 0.05). The biofilm production rate of non-albicans Candida species (41%) was found higher than C. albicans (23%), which the difference was statistically significant (p < 0.05). Amphotericin B and caspofungin were found the most effective antifungals with the MIC90 values of 0.06 microg/ml and 0.5 microg/ml for C. albicans, and 0.5 microg/ml and 1 microg/ml for non-albicans Candida species respectively. The observed positive correlation between the biofilm production and amphotericin B MIC values were found significant (p < 0.05). In conclusion, high biofilm production rates of Candida species may explain the increase in the rate of catheter-related Candida infections.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida; Candidiasis; Caspofungin; Drug Resistance, Fungal; Echinocandins; Fluconazole; Fungemia; Humans; Itraconazole; Lipopeptides; Microbial Sensitivity Tests

A case of arthritis of the right knee caused by Candida lusitaniae in a 29-year-old intravenous drug abuser is described. The diagnosis was based on the isolation of C. lusitaniae from synovial fluid and was supported by the presence of C. lusitaniae-specific DNA and high levels of (1-3)-beta-d-glucan (122 pg ml-1) in the same specimen. While the isolate was susceptible to amphotericin B and fluconazole in vitro, treatment with amphotericin B was not very effective. The patient achieved complete cure with fluconazole therapy only after undergoing synovectomy. To the best of our knowledge, this is the first report of arthritis caused by C. lusitaniae in an intravenous drug user.

Topics: Adult; Amphotericin B; Arthritis, Infectious; Blood Sedimentation; Candida; Candidiasis; Fluconazole; Heroin; Humans; Injections, Intra-Articular; Knee Joint; Male; Protein C; Substance Abuse, Intravenous; Synovial Fluid; Treatment Outcome

To report the clinical, histopathologic, microbiologic, and confocal microscopic features of Candida keratitis after deep anterior lamellar keratoplasty (DALK).. We performed clinical, confocal scan, microbiologic and histopathologic examinations on two corneas from 2 young patients who underwent DALK for keratoconus.. The first patient presented with asymptomatic white to cream-colored interface deposits 2 months after DALK. The confocal scan disclosed clusters of hyperreflective, fine granular deposits at the region of interface, with no evidence of inflammation or hyphaelike structures. The clinical presumption of possible "epithelial downgrowth" was suggested, and because of the progression of these lesions, irrigation of the interface was considered. Finally, penetrating keratoplasty was performed because of a rupture in the Descemet membrane. Histopathologic examination of the cornea disclosed yeastlike structures within the interface area. The microbiologic results of the irrigation fluid showed Candida glabrata. The second patient presented with a symptomatic infiltration of the inferior interface close to the suture site 2.5 months after DALK. The confocal scan showed foci of inflammation with clusters of hyperreflective round-shaped structures that resembled epithelial cells. Clinically, there was a suggestion of epithelial downgrowth, and subsequently, penetrating keratoplasty was performed because of the progression of the lesion. Histopathologic examination of the cornea disclosed an acute and chronic granulomatous keratitis caused by yeastlike structures. The microbiologic results revealed infection with Candida albicans.. These are the first reported occurrences of interface Candida keratitis after DALK and with different confocal features. The clinical and the confocal features of interface Candida keratitis may be similar to those seen in epithelial downgrowth, which may postpone correct diagnosis and treatment. Candida keratitis should be considered in cases of interface deposits after any form of lamellar keratoplasty.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida albicans; Candida glabrata; Candidiasis; Cornea; Corneal Transplantation; Drug Therapy, Combination; Eye Infections, Fungal; Humans; Keratitis; Keratoconus; Keratoplasty, Penetrating; Ketoconazole; Male; Microscopy, Confocal; Natamycin; Postoperative Complications

In the present study, we investigated synergic anticandidal effect of epigallocatechin-O-gallate (EGCG) in a murine model of disseminated candidiasis caused by Candida albicans. In addition, its mechanism was examined. In the animal system, EGCG-given BALB/c mice group intraperitoneally (i.p.) before intravenous (i.v.) inoculation with viable C. albicans yeast cells survived longer than diluent-received (control) mice group (p<0.05). EGCG treatment inhibited the hyphal formation from the yeast form of C. albicans, causing growth-inhibition of the candidal cells. In experiments determining synergic effect, mice given diluent (control), Amp B (amphotericin B; 0.5 mg/kg of body weight), or EGCG (2 mg/kg) had mean survival times (MST) of approximately 10.9, 11.7, and 13.9 d, respectively. However, mice administered combination of Amp B (0.5 mg/kg) plus EGCG (2 mg/kg) had a MST value of 42.1 d, surviving an average of app. 30 d longer than the Amp B alone-received mice groups. The MST value from the combination-treated mice groups was much greater than MST value from mice groups that received four times the Amp B dose. These results indicate that EGCG, which has anticandidal activity causing blockage of the hyphal formation, has the synergism combined with Amp B against disseminated candidiasis.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Catechin; Drug Synergism; Female; Hyphae; Mice; Mice, Inbred BALB C

The objectives of this study were to contrast risk factors, microbiology, and outcomes in patients with invasive candidiasis treated in an intensive care unit (ICU) with those in patients with invasive candidiasis treated outside an ICU and to describe therapeutic results with caspofungin in ICU patients.. We retrospectively identified patients with documented invasive candidiasis who received their first dose of the study drug in the ICU as part of a double-blind randomized trial. Participants were not stratified at entry by their ICU status. Patients received caspofungin (50 mg/d after a 70-mg loading dose) or conventional amphotericin B (0.6-1.0 mg/kg per day) for 10 to 14 days. A favorable response required resolution of signs and symptoms as well as eradication of Candida pathogens.. Of the 224 patients, 97 (43%) received their first dose of the study drug in the ICU. Most patients had well-recognized risk factors for invasive candidiasis, including broad-spectrum antibiotics, central venous catheters, and hyperalimentation. Recent surgery was more common whereas malignancy, neutropenia, and immunosuppression were less common among ICU patients than among non-ICU patients. Candidemia was demonstrated in 81% of ICU patients and in 84% of non-ICU patients. Favorable response rates in the ICU patients vs the non-ICU patients were 68% (95% confidence interval [CI] = 53%, 82%) vs 77% (95% CI = 67%, 87%) for caspofungin and 56% (95% CI = 43%, 69%) vs 67% (95% CI = 55%, 79%) for amphotericin B. After accounting for differences in APACHE (Acute Physiology and Chronic Health Evaluation) II score, neutropenia status, and geographic region, we found that patients initiating the study therapy in an ICU were still more likely to die than patients initiating study therapy outside an ICU. For ICU patients, all-cause mortality rates were 45% (95% CI = 30%, 60%) for caspofungin recipients and 40% (95% CI = 28%, 53%) for amphotericin B recipients, whereas candidiasis-attributable mortality rates were 5% (95% CI = 0%, 12%) for caspofungin recipients and 11% (95% CI = 3%, 19%) for amphotericin B recipients. Overall, drug-related adverse events were reported less often among the ICU patients than among the non-ICU patients.. In ICU patients treated with antifungal therapy, invasive candidiasis is associated with substantial mortality, but most deaths cannot be directly attributed to this infection.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Drug-Related Side Effects and Adverse Reactions; Echinocandins; Female; Fungemia; Humans; Intensive Care Units; Lipopeptides; Logistic Models; Male; Middle Aged; Recurrence; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome; United States

Amphotericin B (AmB) is a drug of choice for treatment of disseminated fungal infections, but its use is often associated with severe adverse effects. Our observation that generic formulations of AmB contain multiple polyene components led us to propose that removal of other polyenes would yield a high purity AmB (AmBHP) with an improved therapeutic index.. To test that premise, AmBHP was first isolated from generic AmB by semi-preparative reverse phase high-pressure liquid chromatography and then its effects were compared in vitro and in vivo with those of commercial AmB formulations.. AmBHP proved to be as active as generic AmB against Candida albicans in vitro and as efficacious as both generic and lipid-complexed AmB in a Candida-infected mouse model. AmBHP appeared to be less toxic to human THP-1 monocytic cells than was generic AmB at low concentrations (<2 microM), as indicated by exclusion of Trypan Blue and incorporation of [(3)H]thymidine. At higher concentrations, effects of AmBHP and generic AmB (Pharma-Tek AmB, PTAmB) on thymidine incorporation and cytosolic calcium concentration were similar. General toxicity to AmBHP in vivo, as indicated by its apparent LD(50) and survival of Candida-infected mice, was roughly twofold less than that to generic or lipid-complexed AmB. Likewise, AmBHP decreased mean glomerular filtration rate about half as much as did a 10-fold lower dose of PTAmB.. Taken together, these data indicate that AmBHP may represent a refinement of currently marketed AmB formulations, offering equal, if not better, efficacy with less toxicity.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Cell Line; Chromatography, High Pressure Liquid; Drugs, Generic; Female; Humans; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Monocytes; Polyenes; Rats; Rats, Sprague-Dawley; Specific Pathogen-Free Organisms

Systemic candidiasis is a rare but life threatening complication in immunosuppressed patients undergoing allogeneic SCT. Combination of new antifungal agents may improve outcome in this patient population. Here, triple anti-mycotic therapy is described in an relapsed ALL patient in urgent need of allogeneic bone marrow transplantation. The patient with T-cell acute lymphoblastic leukemia of thymic differentiation achieved remission after treatment according to the German ALL protocol 07/03. Two months after the consolidation therapy relapse occurred requiring high dose chemotherapy with allogeneic stem cell transplantation. One day after start of the conditioning regimen the patient showed skin manifestations typical for septic mycosis and blood cultures became positive for Candida krusei while on fluconazole prophylaxis. Because of the limited sensibility of fluconazole resistant candida species to liposomal amphotericin B and the high mortality rate in patients with systemic candidiasis, voriconazole was added immediately to liposomal amphotericin B. Since fever did not resolve and the conditioning therapy for allogeneic transplantation was not yet completed caspofungin was added. Skin manifestation responded to this triple anti-mycotic combination and peripheral blood stem cells from an unrelated donor were transplanted. With the triple antifungal therapy the patient finally became afebrile, skin manifestations showed complete resolution and blood cultures became negative. Three months after the onset of systemic candidiasis the patient was fully active with no signs of fungal infection and in haematological and molecular remission. Mycotic sepsis at the start of myeloablative conditioning therapy in heavily pretreated acute leukemia patients is usually considered as not allowing successful allogeneic transplantation. Thus this case demonstrates, that allogeneic stem cell transplantation is feasible in patients presenting with systemic candidiasis if combined antifungal therapy with liposomal amphotericin B, caspofungin and voriconazole is given.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Candidiasis; Caspofungin; Drug Therapy, Combination; Echinocandins; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Leukemia-Lymphoma, Adult T-Cell; Lipopeptides; Liposomes; Male; Peptides, Cyclic; Pyrimidines; Transplantation Conditioning; Transplantation, Homologous; Triazoles; Voriconazole

The aim of this study was to compare the pharmacodynamics of the azole antifungal drugs fluconazole, itraconazole and ketoconazole, and the polyene antifungal amphotericin B, in a mouse model of disseminated Candida albicans infection. In order to directly compare effective serum concentrations of these antifungals, drug concentrations were assayed microbiologically by measuring inhibition of C. albicans mycelial growth (mMIC) in a mouse serum-based assay (serum antifungal titer). Efficacy in the mouse infection model was determined using an organ-based (kidney burden) endpoint. For all four drugs, the serum antifungal titers, 8 hr after administration of single doses of drugs at a range of drug concentrations, correlated closely with C. albicans kidney fungal burden in the mouse model. The results showed that determining serum antifungal titer may be used to accurately represent kidney fungal burden in a mouse model of disseminated candidiasis and allowed direct comparison of the pharmacodynamics of differing classes of antifungal drugs.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Disease Models, Animal; Fluconazole; Itraconazole; Kidney; Mice; Microbial Sensitivity Tests

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Endophthalmitis; Eye Infections, Fungal; Humans; Immunocompromised Host; Postoperative Complications; Pyrimidines; Recurrence; Triazoles; Voriconazole

The in vitro activity of the peptide IB-367, alone or combined with either fluconazole (FLU) or amphotericin B (AMB), was investigated against 25 Candida isolates belonging to five species. IB-367 minimum inhibitory concentrations (MICs) ranged from 2.0 to 32 microg/ml and it was active against both FLU-susceptible and - resistant isolates. A rapid fungicidal activity was observed. Synergism was documented in 41.6% and 44% of IB-367/FLU and IB-367/AMB interactions, respectively. Antagonism was never observed. The broad antifungal activity and the positive interactions with AMB and FLU suggest that IB-367 represents a promising candidate against infections due to Candida spp.

Topics: Amphotericin B; Antifungal Agents; Antimicrobial Cationic Peptides; Candida; Candidiasis; Drug Resistance, Fungal; Drug Synergism; Drug Therapy, Combination; Fluconazole; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Peptides

Topics: Abscess; Amphotericin B; Antifungal Agents; Candidiasis; Dermatomycoses; Extremities; Face; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Culture Media; Fluconazole; Humans; Microbial Sensitivity Tests

Lysosomotropic composition of dialdehyde dextran and amphotericin B had a greater therapeutic effect in mice with systemic candidiasis compared to free amphotericin B. This composition normalized glucocorticoid function of the adrenal glands and decreased the severity of liver destruction at late terms of granulomatous inflammation.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Dextrans; Disease Models, Animal; Drug Therapy, Combination; Granuloma; Liver Diseases; Male; Mice; Mice, Inbred C57BL

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Echinocandins; Female; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Liver Diseases; Peptides, Cyclic; Splenic Diseases

Topics: Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Caspofungin; Drug Therapy, Combination; Echinocandins; Follow-Up Studies; Humans; Kidney Failure, Chronic; Lipopeptides; Male; Peptides, Cyclic; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Risk Assessment; Severity of Illness Index; Treatment Outcome

The polyene antibiotic amphotericin B (AMB) is an effective antifungal agent whose therapeutic potential is limited by poor aqueous solubility and toxicity toward host tissues. Addition of apolipoprotein A-I to a multilamellar phospholipid vesicle dispersion containing 20% (w/w) AMB induces the formation of reconstituted high density lipoprotein (rHDL), with solubilization of the antibiotic. Density gradient ultracentrifugation resulted in flotation of the complexes to a density of 1.16 g/ml, and negative stain electron microscopy revealed a population of disk-shaped particles. Native gradient polyacrylamide gel electrophoresis indicated a particle diameter of approximately 8.5 nm. Absorbance spectroscopy provided evidence for AMB integration into the lipid milieu. AMB-rHDLs were potent inhibitors of Saccharomyces cerevisiae growth, yielding 90% growth inhibition at <1 microg/ml yeast culture. In studies with pathogenic fungal species, similar growth inhibition characteristics were observed. Compared with AMB-deoxycholate micelles, AMB-rHDL displayed greatly attenuated red blood cell hemolytic activity and decreased toxicity toward cultured hepatoma cells. In in vivo studies in immunocompetent mice, AMB-rHDLs were nontoxic at 10 mg/kg, and they showed efficacy in a mouse model of candidiasis at concentrations as low as 0.25 mg/kg. These results indicate that AMB-rHDLs constitute a novel formulation that effectively solubilizes the antibiotic and elicits strong in vitro and in vivo antifungal activity with no observed toxicity at therapeutic doses.

Topics: Amphotericin B; Animals; Antifungal Agents; Apolipoprotein A-I; Aspergillus fumigatus; Candida albicans; Candidiasis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Centrifugation, Density Gradient; Cryptococcus neoformans; Drug Carriers; Erythrocytes; Female; Humans; Lipoproteins, HDL; Mice; Mice, Inbred BALB C; Microscopy, Electron; Phospholipids; Saccharomyces cerevisiae; Spectrophotometry; Spectrophotometry, Ultraviolet; Survival Analysis

To demonstrate the potential value of obtaining routine fungal cultures of donor rims at the time of corneal transplantation and instituting prophylactic therapy in culture-positive cases, even in the absence of clinical evidence of established microbial keratitis or endophthalmitis.. Interventional case report and literature review.. A 69-year-old Saudi man underwent penetrating keratoplasty with donor tissue that was culture-positive for Candida glabrata. The postoperative course was complicated by slight override of the graft associated with an associated epithelial defect, but there was no evidence of microbial keratitis or significant anterior chamber inflammation. Following repair of the graft override on postoperative day 42, the epithelial defect healed. The subsequent clinical course was unremarkable until postoperative day 146, when a deep stromal infiltrate was present at the graft-host junction, associated with a dense endothelial plaque. Cultures of the anterior chamber were positive for Candida glabrata. Treatment with topical and intracameral amphotericin B and systemic fluconazole, along with topical corticosteroids and intracameral t-PA, was successful in eradicating the corneal infiltrate and resolving intraocular inflammation. Four months after treatment was initiated, there was no evidence of recurrent fungal keratitis or endophthalmitis.. This case provides support for the practice of obtaining routine fungal cultures of donor rims at the time of corneal transplantation and for the implementation of prophylactic antifungal therapy in culture-positive cases.

Topics: Aged; Amphotericin B; Anterior Chamber; Candida glabrata; Candidiasis; Cornea; Corneal Ulcer; Disease Transmission, Infectious; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Fungal; Fluconazole; Humans; Keratoplasty, Penetrating; Male; Tissue Donors; Tissue Plasminogen Activator

Reported here is the case of a 72-year-old renal transplant recipient with stenosis of the neo-ureter requiring stents, who was admitted to hospital with pyonephrosis caused by fungus balls. Fluconazole-resistant Candida sake was grown. Treatment with external drainage of the renal pelvis and intravenous and local administration of caspofungin resulted in relief of the obstruction. Eradication of the infection was achieved by surgical removal of the ureter with all stents and construction of a cysto-pyelostomy.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Device Removal; Drug Therapy, Combination; Echinocandins; Fluconazole; Humans; Kidney Transplantation; Lipopeptides; Male; Microbial Sensitivity Tests; Peptides, Cyclic; Reoperation; Stents; Therapeutic Irrigation; Treatment Outcome; Urography

Candidal endocarditis is an uncommon and serious complication of invasive Candida infection in neonates. The aim of this study was to further characterise candidal endocarditis in neonates. Between 1995 and 2000, 56 patients were diagnosed with Candida bloodstream infections (CBSI) in the Neonatal Intensive Care Unit of Schneider Children's Medical Center of Israel. Five of them (9%) developed mycetoma of the right atrium. None of the patients had congenital heart disease or a central venous catheter in the right heart at the time of diagnosis. All were treated with amphotericin B alone or in combination with other antifungals, without surgical intervention. One patient died of the disease and one died later of polymicrobial sepsis and necrotizing enterocolitis. A review of the literature since 1980 yielded an additional 25 cases of candidal endocarditis. For the whole sample (n = 30) survival rate was 73.1%. Six of the 10 patients treated with antifungal agents and surgery survived (60%), compared with 13 of the 20 patients treated only medically (65%) (P = 1.0). Candida endocarditis in neonates differs from fungal endocarditis in adults in risk factors, clinical presentation and outcome. As the outcome of surgical and medical treatment are comparable, antifungal therapy alone may be a valid therapeutic option in high-risk cases.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Drug Therapy, Combination; Endocarditis; Enterocolitis; Fatal Outcome; Female; Fungemia; Heart Atria; Humans; Infant, Newborn; Mycetoma; Premature Birth; Review Literature as Topic; Risk Factors; Sepsis; Thinness; Thoracic Surgery; Treatment Outcome

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Drug Therapy, Combination; Female; Humans; Itraconazole; Kidney Transplantation; Liver Diseases

Recent open label studies have suggested that dosing amphotericin B (AMB) by continuous infusion (CI) may reduce drug-associated infusion reactions and nephrotoxicity. In vitro and in vivo pharmacodynamic (PD) data, however, do not consistently support the concept of CI dosing based on the concentration-dependent activity of this agent and in vitro studies with AMB rarely account for the drug's high degree of protein binding. Therefore, we compared the PD activity of simulated continuous versus rapid infusion strategies of AMB in killing of AMB-susceptible and -resistant Candida species using an in vitro pharmacodynamic model.. Time-kill curves were performed with Candida albicans (Etest MIC 0.38 mg/L) and Candida lusitaniae (MIC 1.5 mg/L) at AMB concentrations between 0 and 16 mg/L in the absence and presence of 4 and 8% human serum albumin (HSA). A one-compartment in vitro pharmacodynamic model was used to simulate the steady-state PK parameters of bolus and CI AMB.. The fungicidal activity of AMB was attenuated by the presence of HSA for both Candida species tested. The EC50 for each isolate significantly increased in the presence of 4% HSA (P<0.05), and fungicidal activity was completely abated for C. lusitaniae when HSA concentrations were increased to 8%. No substantial differences in the rate or extent of AMB killing were observed between rapid infusion or CI dosing and neither regimen produced fungicidal activity in the presence of HSA.. The presence of HSA changes the in vitro PD of AMB. In our model, CI and rapid infusion dosing of AMB exhibited similar activity when attempts were made to correct for protein binding that is likely to occur in vivo.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Combinations; Half-Life; Humans; In Vitro Techniques; Infusions, Intravenous; Microbial Sensitivity Tests; Models, Biological; Serum Albumin

The antifungal activity of the essential oil from Cinnamomum cassia, alone or combined with amphotericin B, a drug widely used for most indications despite side-effects was investigated. The composition of the oil was analysed by GC/MS and characterized by its very high content of cinnamaldehyde (92.2%). The minimal inhibitory concentration (MIC 80%), used to evaluate the antifungal activity against Candida albicans, was determined by a macrobroth dilution method followed by a modelling of fungal growth. The essential oil of Cinnamomum cassia exhibited strong antifungal effect (MIC 80% = 0.169 microL/mL and K(aff) = 18,544 microL/mL). A decrease of the MIC 80% of amphotericin B was obtained when the culture medium contained essential oil concentrations ranging from 0.08 to 0.1 microL/mL. The strongest decrease (70%) was obtained when the medium contained 0.1 microL/mL of essential oil. This potentiation of amphotericin B obtained in vitro may show promise for the development of less toxic and more effective therapies especially for the treatment of HIV infection.

Topics: Acrolein; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Cinnamates; Cinnamomum aromaticum; Drug Synergism; Gas Chromatography-Mass Spectrometry; Microbial Sensitivity Tests; Oils, Volatile; Phytotherapy; Plant Extracts; Regression Analysis

Anidulafungin, an echinocandin, is in late stage development for the treatment of fungal infections. We investigated the activity of anidulafungin in combination with other antifungal agents (fluconazole, itraconazole, ketoconazole, amphotericin B and 5-fluorocytosine) against four isolates each of Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis, and two isolates of Candida krusei using a macrobroth chequerboard method with interactions evaluated by fractional inhibitory concentration indices (FICIs). Additive activity (FICI > 0.5 to 1) or indifference (FICI > 1 to < 4) was observed in 85 of 90 interactions of anidulafungin with another antifungal agent. Synergy with itraconazole (FICIor=4), a drug rarely used systemically, was noted for four strains of C. tropicalis. The combination of anidulafungin and amphotericin B demonstrated additive activity for each of the 18 isolates of Candida tested. These results suggest additional studies are warranted, for example in animal models, to evaluate further the potential of combination antifungal therapy with anidulafungin for Candida infections.

Topics: Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candida tropicalis; Candidiasis; Drug Interactions; Echinocandins; Flucytosine; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Peptides, Cyclic

It is generally accepted that the lipid formulations of amphotericin B (AMB) are not as potent as conventional AMB on a milligram-per-kilogram basis. We used a neutropenic murine disseminated candidiasis model to compare the in vivo potencies of AMB, liposomal AMB (L-AMB), and AMB lipid complex (ABLC) pharmacodynamically. The pharmacokinetics of the antifungals were examined in serum and in three organs commonly seeded in disseminated candidiasis (kidneys, liver, and lung). Both single-dose time-kill studies and multiple-dosing-regimen studies were used with each of the compounds. Determinations of the numbers of CFU in the kidneys were performed following the administration of three escalating single doses of the polyenes at various times over 48 h. The areas under the time-kill curves (AUTKs) for each dose level of the drugs were compared by analysis of variance (ANOVA). In the multiple-dosing-regimen studies with five Candida isolates, AMB, L-AMB, and ABLC were administered daily for 72 h. The organism burdens in the mouse kidneys were similarly used as the treatment end point. Additional multiple regimen-dosing-studies were performed with a single Candida albicans isolate, and the microbiologic outcomes in four internal organs (kidneys, liver, spleen, and lung) were examined at the end of therapy (48 h). The relationship between the dose and the drug exposure expressed by the pharmacokinetics of the dosing regimens in serum and organ tissue were analyzed by using a maximum-effect model. ANOVA was used to compare the drug exposures necessary to achieve the 25% effective dose (ED25), ED50, ED75, and 1 log10 killing. Comparison of AUTKs suggested that AMB was 4.3- to 5.9-fold more potent than either ABLC or L-AMB. The time-kill curves for both lipid formulations were very similar. In the multiple-dosing-regimen studies, AMB was 5.0- to 8.0-fold more potent than each of the lipid formulations against five Candida isolates in the kidneys. Similar differences in potency (5.1- to 7.2-fold) were observed in the other end organs. The difference in pharmacokinetics in serum accounted for much of the difference in potency between AMB and ABLC (ratio of serum ABLC area under the curve of effective doses to serum AMB area under the curve of effective doses, 1.2). The differences in the kinetics in the various end organs between AMB and L-AMB were better at explaining the disparate potencies at these infection sites (ratio of organ L-AMB area under the curve of eff

Topics: Amphotericin B; Animals; Antifungal Agents; Area Under Curve; Candida; Candidiasis; Disease Models, Animal; Female; Lipids; Liposomes; Mice; Mice, Inbred ICR

To determine the efficacy of oral amphotericin B for the prevention of Candida bloodstream infection in the pediatric intensive care unit.. Retrospective, nonrandomized, historic-control study.. Multidisciplinary pediatric intensive care unit at a university-affiliated children's medical center.. Study group included all patients admitted to the pediatric intensive care unit from January 1, 1998, to December 31, 1999, who required mechanical ventilation and who were admitted for >7 days. The control group included all patients admitted for >7 days who needed mechanical ventilation from January 1, 1994, to December 31, 1997.. Oral amphotericin B suspension, 50 mg every 8 hrs, administered to all study group patients soon after initiation of mechanical ventilation and terminating after weaning.. The rates of Candida bloodstream infection were compared between the study and control groups.. Candida species were isolated from blood cultures in 5 of 185 (2.1%) and 21 of 196 (10.7%) patients in the study and control groups, respectively (p= .0038). There was also a statistically significant (p= .017) decrease in Candida bloodstream infection rate in all patients admitted to the pediatric intensive care unit for >7 days during the study period compared with the Candida bloodstream infection rate during the control period.. Prophylactic administration of oral amphotericin B may lead to a significant decrease in the rate of Candida bloodstream infection in ventilated pediatric intensive care unit patients.

Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Candidiasis; Child; Critical Illness; Cross Infection; Fungemia; Humans; Intensive Care Units, Pediatric; Respiration, Artificial; Retrospective Studies

Consecutive Candida glabrata isolates recovered from a patient in an intensive care unit were resistant to amphotericin B (minimum inhibitory concentration, up to 32 mu g/mL; determined by Etest [AB Biodisk]). Analyses at the national reference laboratory showed that some isolates were also resistant to azoles and caspofungin. In this study, 4 isolates were studied thoroughly using susceptibility assays and a mouse model and to determine clonality.. Different broth microdilution tests, Etests, and time-kill studies for antifungals were performed in different media. Three of the 4 isolates were examined in an in vivo experiment, in which mice were challenged intravenously with 1 of 3 isolates and treated daily with amphotericin B, caspofungin, or saline. For the clonality studies, arbitrarily primed polymerase chain reaction (PCR) was performed with the 4 isolates, 8 isolates obtained from nonrelated patients, and a reference strain.. The murine model indicated that 1 isolate was resistant to amphotericin B, 1 had intermediate susceptibility, and 1 was fully susceptible. Two of the 3 isolates were resistant to caspofungin. Microdilution methods did not reliably differentiate between amphotericin B-susceptible and -resistant isolates. All assays identified caspofungin-susceptible and -resistant isolates. Arbitrarily primed PCR showed that the 4 isolates probably were of clonal origin.. We have documented the emergence of amphotericin B-resistant and caspofungin-resistant C. glabrata isolates during treatment of a critically ill liver transplant recipient. Only the Etest predicted amphotericin B resistance in the isolates. We recommend that important fungal strains recovered from patients who are receiving antifungal therapy should be tested for susceptibility to the antifungal drug used, because resistance can be present initially or may occur during treatment.

Topics: Aged; Amphotericin B; Animals; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Critical Illness; Echinocandins; Female; Humans; Lipopeptides; Mice; Microbial Sensitivity Tests; Peptides, Cyclic; Polymerase Chain Reaction

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Catheterization, Central Venous; Equipment Contamination; Humans; Pyrimidines; Triazoles; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Child; Fungemia; Humans; Intensive Care Units, Pediatric; Respiration, Artificial

One hundred seven Candida bloodstream isolates (51 C. albicans, 24 C. glabrata, 13 C. parapsilosis, 13 C. tropicalis, 2 C. dubliniensis, 2 C. krusei, and 2 C. lusitaniae strains) from patients treated with amphotericin B alone underwent in vitro susceptibility testing against amphotericin B using five different methods. Fifty-four isolates were from patients who failed treatment, defined as death 7 to 14 days after the incident candidemia episode, having persistent fever of >or=5 days' duration after the date of the incident candidemia, or the recurrence of fever after two consecutive afebrile days while on antifungal treatment. MICs were determined by using the Clinical Laboratory Standards Institute (formally National Committee for Clinical Laboratory Standards) broth microdilution procedure with two media and by using Etest. Minimum fungicidal concentrations (MFCs) were also measured in two media. Broth microdilution tests with RPMI 1640 medium generated a restricted range of MICs (0.125 to 1 microg/ml); the corresponding MFC values ranged from 0.5 to 4 microg/ml. Broth microdilution tests with antibiotic medium 3 produced a broader distribution of MIC and MFC results (0.015 to 0.25 microg/ml and 0.06 to 2 microg/ml, respectively). Etest produced the widest distribution of MICs (0.094 to 2 microg/ml). However, none of the test formats studied generated results that significantly correlated with therapeutic success or failure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Child; Child, Preschool; Female; Fungemia; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Middle Aged; Treatment Failure

We describe a 9-yr-old boy who received the highest cumulative dose so far reported of liposomal amphotericin B. The patient underwent an allogeneic bone marrow transplantation (BMT) for adrenoleucodystrophy, after a conditioning regimen with busulfan, thiothepa and cyclophosphamide. Rabbit antithymoglobulin, cyclosporin and prednisone were used as prophylaxis against graft vs. host disease (GVHD). Post-transplant Epstein-Bar-virus-related lymphoma was diagnosed on day +68 and was treated with donor-derived lymphocytes. The patient developed a severe form of GVHD, and a progressive worsening of his neurological status because of progression of his underlying disease. Death from septic shock occurred 23 months after BMT. During prolonged hospitalization, 19,750 mg of liposomal amphotericin B, about 1000 mg/kg, were given for prophylactic or empirical therapeutic purposes without significant nephrotoxicity. This case suggests that liposomal amphotericin B is safe and well-tolerated even if is administered for long periods and a cumulative dose fivefold greater than the nephrotoxic threshold of amphotericin B deoxycholate is achieved.

Topics: Adrenoleukodystrophy; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Candidiasis; Child; Creatinine; Disease Progression; Epstein-Barr Virus Infections; Fatal Outcome; Graft vs Host Disease; Humans; Kidney; Kidney Diseases; Liposomes; Lymphoma; Male; Pseudomonas Infections; Shock, Septic; T-Lymphocytes, Cytotoxic; Transplantation Conditioning

Candida lusitaniae is an opportunistic yeast pathogen that has the ability to develop resistance to amphotericin B (AmB). The mechanism(s) for this resistance is not well understood, although there are data supporting mutations in sterol pathways and other data supporting phenotypic switching (PS). The goal of this study was to determine whether C. lusitaniae has a PS system and to characterize any phenotypes, including any changes in AmB MICs. When 10(4) CFU of an AmB-resistant (MIC of 16 to 32 microg/ml) clinical strain was plated on yeast-peptone-dextrose (YPD) agar with 1 mM CuSO(4), three colony colors were observed: light brown (LB) >> dark brown (DB) > white (W), similar to the result for Candida glabrata. Switching did occur with high AmB resistance (MIC of 256 microg/ml) being associated with W, whereas LB and DB colonies had MICs of 2 to 8 microg/ml and 2 to 16 microg/ml, respectively. Filamentation (pseudohyphae) was associated with DB colonies. All phenotypes occurred spontaneously with greater frequency ( approximately 10(-2) to 10(-4)) than spontaneous mutations, and all phenotypes were reversible, fulfilling the two PS criteria. High AmB MICs were always associated with W colonies but not with all W colonies. Detection of PS on YPD-CuSO(4) is also similar to that in Candida glabrata, and we hypothesize that this is due to similarities in metallothionein gene expression. Phenotypic switching represents a key strategy in C. lusitaniae that confers a selective advantage during environmental challenges, including the ability to switch to AmB resistance.

Topics: Agar; Amphotericin B; Candida; Candidiasis; Copper Sulfate; Culture Media; Drug Resistance, Fungal; Gene Expression Regulation, Fungal; Microbial Sensitivity Tests; Phenotype

Bloodstream infections due to Candida spp. are associated with significant mortality and morbidity. This study analysed the epidemiology and outcome of candidemia cases in a teaching hospital in central Taiwan.. We retrospectively studied the clinical characteristics and antifungal susceptibility of isolates and risk factors for mortality in 91 cases of candidemia treated from January 1, 2001 to June 30, 2003.. The mean age of the patients was 67 years (range, 30-90 years). Three episodes (3%) were community acquired. Adequate antifungal therapy was given to 78 patients (78%). Cancer (38.5%) and diabetes mellitus (36.3%) were the 2 most common underlying diseases. The most frequent risk factors identified for candidemia were prior broad-spectrum antibiotic use (84.6%), central venous catheterization (83.5%) and Candida colonization (79.5%). The most frequent isolates were Candida albicans (64.8%) and Candida tropicalis (19.8%). All of the C. albicans and C. tropicalis isolates were sensitive to fluconazole (minimal inhibitory concentration

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; APACHE; Candida; Candidiasis; Catheterization, Central Venous; Community-Acquired Infections; Cross Infection; Diabetes Complications; Female; Fluconazole; Fungemia; Hospitals; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Neoplasms; Prognosis; Retrospective Studies; Risk Factors; Shock; Statistics as Topic; Taiwan

Blood stream infections caused by Candida glabrata are difficult to manage. We describe a patient who underwent an allogeneic peripheral stem cell transplantation for acute myeloid leukaemia. The patient developed C. glabrata fungaemia that was refractory to liposomal amphotericin B therapy. After changing the therapy to caspofungin, blood cultures became sterile within two days and the patient recovered clinically. The patient died shortly after due to graft-versus-host disease and at autopsy there was no evidence of residual or persistent Candida infection. Caspofungin was effective in liposomal amphotericin-B refractory C. glabrata fungaemia and proved to rapidly clear the infection. Treatment options for candidaemia are discussed.

Topics: Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Echinocandins; Female; Humans; Lipopeptides; Liposomes; Middle Aged; Peptides, Cyclic; Stem Cell Transplantation; Treatment Failure

Topics: Amphotericin B; Antibodies, Monoclonal; Antifungal Agents; Candidiasis; HSP90 Heat-Shock Proteins; Humans; Recombinant Proteins

A 62-year-old man with amphotericin B-resistant Candida krusei spondylodiscitis, following an episode of candidemia caused by the same strain, was successfully treated with caspofungin plus voriconazole. Amphotericin B fungicidal concentrations were better predictors of the clinical outcome than were MICs. This is the first case of C. krusei spondylodiscitis reported in the literature.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Discitis; Drug Resistance, Fungal; Echinocandins; Humans; Lipopeptides; Magnetic Resonance Imaging; Male; Microbial Sensitivity Tests; Middle Aged; Peptides, Cyclic; Pyrimidines; Triazoles; Voriconazole

In the present study we evaluated the pharmacokinetics and toxicity of amphotericin B in immunomodulator tuftsin-loaded liposomes in a murine model.. Stability of amphotericin B liposomes was tested by incubating one volume of liposomal formulations of amphotericin B with nine volumes of serum. The pharmacokinetics of amphotericin B in Candida albicans-infected mice treated with conventional and tuftsin-loaded amphotericin B liposomes was evaluated over a period of 24 h. In vitro toxicity of amphotericin B deoxycholate, as well as amphotericin B liposomes, was tested by incubation with human erythrocytes for 1 h at 37 degrees C. To assess amphotericin B-induced in vivo toxicity, BALB/c mice were injected with three doses of amphotericin B deoxycholate, as well as amphotericin B liposomal formulations on days 1, 2 and 3 post C. albicans infection. Blood from treated mice was taken by retro-orbital puncture to test renal function parameters such as serum creatinine and urea.. In vitro stability studies revealed that tuftsin-bearing amphotericin B liposomes released only 11% of the total liposomal amphotericin B in the serum, while it was found to be 19% from identical tuftsin-free amphotericin B liposomes. Both tuftsin-loaded as well as tuftsin-free liposomal formulations of amphotericin B induced approximately 20% haemolysis of erythrocytes at a dose of 40 mg/L, while the same amount of drug in amphotericin B deoxycholate caused 100% lysis of the erythrocytes. Pharmacokinetic studies revealed that subsequent to administration of various formulations of amphotericin B, there was 32 mg/L amphotericin B in the systemic circulation of mice treated with tuftsin-bearing amphotericin B liposomes, while it was 25 mg/L for amphotericin B liposomes, 4 h post drug administration. In vivo toxicity studies demonstrated that the amphotericin B deoxycholate formulation induced elevations in serum creatinine (approximately 300% of control) and blood urea (approximately 380% of control) values, while these values were substantially less (blood urea approximately 150% of control and serum creatinine approximately 210% of control) in the animals treated with the tuftsin-loaded amphotericin B liposomal formulation. Further, the administration of amphotericin B deoxycholate (1 mg/kg) in BALB/c mice at a dose of 1 mg/kg body weight led to the accumulation of 18.6 +/- 5.25 g/kg (of amphotericin B) in kidneys. On the other hand, administration of liposomal amphotericin B and tuftsin-bearing liposomal amphotericin B at a dose of 5 mg/kg body weight resulted in accumulation of 8.8 +/- 2.0 and 4.0 +/- 1.6 g/kg of amphotericin B, respectively, in the kidneys of treated animals.. Co-administration of immunomodulator tuftsin along with liposomal formulations of amphotericin B successfully minimizes toxicity, as well as other side effects of the drug. Interestingly, tuftsin also increased the stability of liposomal amphotericin B. Superior efficacy, reliable safety and favourable pharmacodynamics of tuftsin-loaded amphotericin B liposomes suggest their potential therapeutic value in the management of fungal infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Combinations; Drug Stability; Immunologic Factors; Liposomes; Mice; Mice, Inbred BALB C; Tuftsin

The in vitro activity of the novel triazole antifungal agent posaconazole (Noxafil; SCH 56592) was assessed in 45 laboratories against approximately 19,000 clinically important strains of yeasts and molds. The activity of posaconazole was compared with those of itraconazole, fluconazole, voriconazole, and amphotericin B against subsets of the isolates. Strains were tested utilizing Clinical and Laboratory Standards Institute broth microdilution methods using RPMI 1640 medium (except for amphotericin B, which was frequently tested in antibiotic medium 3). MICs were determined at the recommended endpoints and time intervals. Against all fungi in the database (22,850 MICs), the MIC(50) and MIC(90) values for posaconazole were 0.063 microg/ml and 1 mug/ml, respectively. MIC(90) values against all yeasts (18,351 MICs) and molds (4,499 MICs) were both 1 mug/ml. In comparative studies against subsets of the isolates, posaconazole was more active than, or within 1 dilution of, the comparator drugs itraconazole, fluconazole, voriconazole, and amphotericin B against approximately 7,000 isolates of Candida and Cryptococcus spp. Against all molds (1,702 MICs, including 1,423 MICs for Aspergillus isolates), posaconazole was more active than or equal to the comparator drugs in almost every category. Posaconazole was active against isolates of Candida and Aspergillus spp. that exhibit resistance to fluconazole, voriconazole, and amphotericin B and was much more active than the other triazoles against zygomycetes. Posaconazole exhibited potent antifungal activity against a wide variety of clinically important fungal pathogens and was frequently more active than other azoles and amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Candida; Candidiasis; Cryptococcosis; Cryptococcus; Drug Resistance, Fungal; Fluconazole; Fungi; Humans; In Vitro Techniques; Itraconazole; Microbial Sensitivity Tests; Mycoses; Pyrimidines; Triazoles; Voriconazole

To evaluate the efficacy and toxicity of sustained intravitreal amphotericin B drug delivery system (DDS) on experimental rabbit fungal endophthalmitis of Candida albicans.. Fifty New Zealand rabbits received central vitrectomy were followed by Candida albicans suspension (10(4) colony forming unit, cfu) injection. Rabbits were grouped randomly into five with ten in each as follows: Group A, endophthalmitis control group; Group B, DDS of vehicle alone; Group C, topical treatment with amphotericin B eyedrop; Group D, 5 microg of amphotericin B intravitreal injection every week for two weeks; Group E, DDS contained 1 mg of amphotericin B. Slit-lamp and indirect-ophthalmoscope were performed at different time for two months and vitreous opacity was compared between each group. The intraocular drug concentration was measured with high performance liquid chromatography (HPLC). Light and electron microscope were conducted to evaluate the toxicity of DDS and the effect of vehicle on intraocular structure. Electroretinography (ERG) was employed to evaluate the function of retina before and after the implantation of DDS.. Endophthalmitis was obviously inhibited in group E while vitreous was still opacity in other groups. The drug concentration in vitreous cavity was stable and remained for two months in group E while rapidly went down two weeks later in group D. No toxic evidence was found in ocular, liver and kidney tissue and retinal ultrastructure was normal. There was no difference in ERG study before and after the DDS was implanted.. Sustained intravitreal amphotericin B DDS can significantly suppress the formation of fungal colony and inhibit the development of infection with long and stable intraocular drug concentration maintenance. The vehicle and amphotericin B DDS are safe to intraocular structure.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Drug Delivery Systems; Endophthalmitis; Polyesters; Rabbits; Random Allocation

Topics: Aged; Amphotericin B; Antifungal Agents; Anxiety Disorders; Arthritis, Infectious; Candida glabrata; Candidiasis; Chest Pain; Diagnosis, Differential; Dyspnea; Female; Humans; Infusions, Intravenous; Knee Prosthesis; Liposomes; Prosthesis-Related Infections; Recurrence; Syndrome

This is the first report to investigate the antifungal susceptibility of 21 clinical isolates of seven Candida species to epigallocatechin 3-O-gallate (EGCg) and to compare with six antifungal agents, amphotericin B (AMPH), fluconazole (FLCZ), flucytosin (5FC), itraconazole (ITCZ), micafungin (MCFG), and miconazole (MCZ), using a method following the National Committee for Clinical Laboratory Standards (NCCLS) M27-A guidelines. Among the tested species, Candida glabrata exhibited the highest susceptibility to EGCg (MIC50, 0.5-1 microg/ml and MIC90, 1-2 microg/ml) compared favorably with FLCZ, although they were slightly less susceptible than to AMPH, 5FC, MCFG, ITCZ, and MCZ. Candida guilliemondii and Candida parapsilosis (MIC50, 1-4 microg/ml and MIC90, 2-16 microg/ml) were also susceptible to EGCg, although they appear to be slightly less susceptible to EGCg than C. glabrata and the other antifungal agents tested. Moreover, the susceptibility of Candida krusei strains (MIC50, 2 microg/ml and MIC90, 4-8 microg/ml) to EGCg was approximately 2- to 8-fold higher than those of 5FC and FLCZ. Our data indicate that EGCg can inhibit clinically pathogenic Candida species, although the concentrations of EGCg for antifungal susceptibility were slightly higher than those of tested antifungal agents on the whole. Based on these results, we suggest that EGCg may be effectively used as a possible agent or adjuvant for antifungal therapy in Candidiasis.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Catechin; Dose-Response Relationship, Drug; Echinocandins; Fluconazole; Flucytosine; Humans; Itraconazole; Lipopeptides; Lipoproteins; Micafungin; Miconazole; Microbial Sensitivity Tests; Peptides, Cyclic; Species Specificity

Matrix material was extracted from biofilms of Candida albicans and Candida tropicalis and analysed chemically. Both preparations contained carbohydrate, protein, hexosamine, phosphorus and uronic acid. However, the major component in C. albicans matrix was glucose (32%), whereas in C. tropicalis matrix it was hexosamine (27%). Biofilms of C. albicans were more easily detached from plastic surfaces by treatment with the enzyme lyticase (beta-1,3-glucanase) than were those of C. tropicalis. Biofilms of C. albicans were also partially detached by treatment with proteinase K, chitinase, DNase I, or beta-N-acetylglucosaminidase, whereas C. tropicalis biofilms were only affected by lipase type VII or chitinase. To investigate a possible role for the matrix in biofilm resistance to antifungal agents, biofilms of C. albicans were grown under conditions of continuous flow in a modified Robbins device (MRD). These biofilms produced more matrix material than those grown statically, and were significantly more resistant to amphotericin B. Biofilms of C. tropicalis synthesized large amounts of matrix material even when grown statically, and such biofilms were completely resistant to both amphotericin B and fluconazole. Mixed-species biofilms of C. albicans and a slime-producing strain of Staphylococcus epidermidis (RP62A), when grown statically or in the MRD, were also completely resistant to amphotericin B and fluconazole. Mixed-species biofilms of C. albicans and a slime-negative mutant of S. epidermidis (M7), on the other hand, were completely drug resistant only when grown under flow conditions. These results demonstrate that the matrix can make a significant contribution to drug resistance in Candida biofilms, especially under conditions similar to those found in catheter infections in vivo, and that the composition of the matrix material is an important determinant in resistance.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida albicans; Candida tropicalis; Candidiasis; Drug Resistance, Fungal; Fluconazole; Humans; Polymers; Polyvinyl Chloride; Staphylococcus epidermidis

The aim of this study was to determine the in vitro susceptibility of amphotericin B, fluconazole and itraconazole, to several Candida spp recovered from blood cultures on hospitalized patients at the University Hospital of Maracaibo, Venezuela. The determination of the antifungal susceptibility was carried out according to the microdilution method in broth developed by The European Committee for Antimicrobial Susceptibility Testing (EUCAST). The profile of susceptibility of the 74 isolates showed that all the studied species were susceptible to amphotericin B, and 97.2% and 89.2% to fluconazole and itraconazole, respectively.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Fluconazole; Fungemia; Hospitals, University; Humans; Itraconazole; Microbial Sensitivity Tests; Venezuela

Amphotericin B (AMB), micafungin, and caspofungin MICs, minimal fungicidal concentrations, and time-killing curves were determined in the presence and absence of 10% inactivated serum. AMB was the only agent with consistent killing activity (time required to achieve 99.9% of growth reduction was 2.1 to 3.2 h). The presence of serum enhanced caspofungin activity but lowered those of micafungin and AMB.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Echinocandins; Kinetics; Lipopeptides; Lipoproteins; Micafungin; Microbial Sensitivity Tests; Peptides, Cyclic

A 53-year-old woman with an intraabdominal infection secondary to Candida albicans experienced hyperbilirubinemia after receiving amphotericin B in two different formulations--amphotericin B deoxycholate and amphotericin B lipid complex. Only a few case reports of amphotericin B-induced hyperbilirubinemia have been documented in the literature, each with different patterns of corresponding abnormalities in liver function tests. The unpredictable nature of this adverse effect warrants monitoring of bilirubin levels and liver function at baseline and potentially during therapy with amphotericin B, regardless of formulation, dosage, or duration of therapy.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Carcinoma, Non-Small-Cell Lung; Deoxycholic Acid; Drug Combinations; Female; Humans; Hyperbilirubinemia; Liver; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols

We describe a case of recurrent Candida glabrata fungemia that became unresponsive to fluconazole treatment. Posttreatment isolates from blood and vaginal cultures of the immunocompetent patient were azole resistant and exhibited upregulated expression of CgCDR1/CgCDR2 efflux pumps compared to the original isolates. Amphotericin B therapy eradicated the infection.

Topics: Adult; Amphotericin B; Antifungal Agents; Azoles; Blood; Candida glabrata; Candidiasis; Drug Resistance, Fungal; Female; Fungemia; Gene Expression Regulation, Fungal; Genes, Fungal; Humans; Recurrence; Vagina

A liposomal formulation of Amphotericin B (AmBisome), with small unilamellar vesicles containing amphotericin B, shows characteristic pharmacokinetics as liposomes, and in consequence, has different pharmacological activity and toxicity from amphotericin B deoxycholate (Fungizone). In this study, we evaluated the antifungal pharmacodynamic characteristics of AmBisome against Candida albicans using the in vitro time-kill method and murine systemic infection model. A time-kill study indicated that the in vitro fungicidal activities of AmBisome and Fungizone against C. albicans ATCC 90029 increased with increasing drug concentration. For in vivo experiments, leucopenic mice were infected intravenously with the isolate 4 hr prior to the start of therapy. The infected mice were treated for 24 hr with twelve dosing regimens of AmBisome administered at 8-, 12-, 24-hr dosing intervals. Correlation analysis between the fungal burden in the kidney after 24 hr of therapy and each pharmacokinetic/pharmacodynamic parameter showed that the peak level/MIC ratio was the best predictive parameter of the in vivo outcome of AmBisome. These results suggest that AmBisome, as well as Fungizone, has concentration-dependent antifungal activity. Furthermore, since AmBisome can safely achieve higher concentrations in serum than Fungizone, AmBisome is thought to have superior potency to Fungizone against fungal infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Disease Models, Animal; Dose-Response Relationship, Drug; Kidney; Leukopenia; Male; Mice; Microbial Sensitivity Tests

In order to determine the local epidemiology of candidemia, Candida strains isolated between 1994 and 2000 were identified to species level; antifungal resistance patterns and DNA fingerprints were analyzed. Identification of Candida strains (n: 140) was performed with germ tube test and carbohydrate assimilation reactions. Minimal inhibitory concentrations were determined using a commercial test for 5-flucytosine and the broth macrodilution method according to NCCLS for fluconazole and amphotericin B. Molecular relatedness was determined by restriction endonuclease analysis of genomic DNA followed by probe hybridization. C. albicans (37.2%), C. parapsilosis (32.2%), and C. tropicalis (12.2%) comprised 114 (81.4%) of 140 isolates. Susceptibility tests did not reveal resistance to amphotericin B in any of the Candida isolates. Fluconazole resistance was detected in one isolate of C. krusei, and 5-flucytosine resistance in two C. tropicalis isolates and one C. albicans isolate. Significantly higher frequency of clusters with identical strains in C. parapsilosis and C. tropicalis was detected compared to C. albicans. Pediatric wards are particularly important in the nosocomial transmission of non-albicans candida species.

Topics: Amphotericin B; Antifungal Agents; Blotting, Southern; Candida; Candidiasis; Cross Infection; DNA Fingerprinting; Drug Resistance, Fungal; Fluconazole; Flucytosine; Fungemia; Hospital Units; Humans; Microbial Sensitivity Tests; Turkey

Candidemia is often fatal, especially in patients with persistent neutropenia. New therapies are needed. We performed 24-h pharmacodynamic studies to compare the efficacies of anidulafungin, fluconazole, and amphotericin B in neutropenic mice with disseminated candidiasis caused by one of three strains of Candida glabrata. Anidulafungin produced a maximal fungal kill (E(max)) of 1.4 to 1.9 log(10) CFU/g in kidneys and was not influenced by resistance to either fluconazole or amphotericin B. Fluconazole produced an E(max) of 1.3 log(10) CFU/g in mice infected with fluconazole-susceptible C. glabrata, but the E(max) was 0 for mice infected with a C. glabrata strain that had a fluconazole MIC of >/=32 mg/liter. Amphotericin B achieved an E(max) of 4.2 log(10) CFU/g in mice infected with amphotericin B-susceptible C. glabrata, but the E(max) was 0 for mice infected with a C. glabrata strain with an amphotericin B MIC of 2 mg/liter. In all instances, anidulafungin's maximal microbial kill was superior to that of fluconazole. Next, we performed a 96-h anidulafungin pharmacokinetic-pharmacodynamic study. Anidulafungin exhibited delayed peak concentrations in kidneys compared to those in serum, after which the concentrations declined, with a serum terminal half-life of 21.6 (+/-4.6) h. This was accompanied by a persistent 96-h decrease in the kidney fungal burden after treatment with a single anidulafungin dose of >/=8 mg/kg of body weight. This pharmacokinetic-pharmacodynamic picture of anidulafungin persistence in tissues and the resultant persistent fungal decline should be exploited to improve the efficacy of anidulafungin therapy for candidemia.

Topics: Algorithms; Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Area Under Curve; Candida glabrata; Candidiasis; Colony Count, Microbial; Dose-Response Relationship, Drug; Echinocandins; Female; Fluconazole; Mice; Microbial Sensitivity Tests; Neutropenia; Peptides, Cyclic

Topics: Amphotericin B; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Candidiasis; Drug Combinations; HSP90 Heat-Shock Proteins; Humans; Phosphatidylcholines; Phosphatidylglycerols; Recombinant Proteins; Research Design; Survival Analysis

A severe case of Candida albicans panophthalmitis, probably prompted by an underlying diabetes mellitus, is reported. The course was prolonged (more than 16 weeks), although favourable after treatment with several antifungal agents, all with a predictable activity in this ocular complication and with proven susceptibility in the present case: fluconazole, liposomal amphotericin B, caspofungin, and voriconazole.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Caspofungin; Echinocandins; Fluconazole; Humans; Lipopeptides; Male; Middle Aged; Panophthalmitis; Peptides, Cyclic; Pyrimidines; Triazoles; Voriconazole

To develop proper treatments for patients who do not respond to current antifungal treatments, we tested new combinations of antifungal drugs for treating disseminated infections by Candida glabrata in a murine model.. Mice were rendered neutropenic by intraperitoneal cyclophosphamide and intravenous 5-fluorouracil administration. The animals were infected intravenously with 2 x 10(8) cfu of C. glabrata. The efficacies of micafungin combined with amphotericin B, fluconazole or flucytosine, and of amphotericin B combined with fluconazole were evaluated by survival and tissue burden reduction.. Micafungin plus amphotericin B was the most effective combination at reducing tissue burden. Micafungin at 10 mg/kg combined with amphotericin B at 0.75, 1.5 or 3 mg/kg prolonged survival with respect to the monotherapies, but only the second combination showed a synergistic effect in reducing fungal load in spleen and kidney. Amphotericin B at 1.5 mg/kg combined with micafungin at 5, 10 or 20 mg/kg reduced tissue burden with respect to the monotherapies, but the effects of the three combinations were very similar. These results suggest that amphotericin B in combination with micafungin is promising for the treatment of disseminated C. glabrata infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida glabrata; Candidiasis; Colony Count, Microbial; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Echinocandins; Fluconazole; Flucytosine; Immunocompromised Host; Kidney; Lipopeptides; Lipoproteins; Micafungin; Mice; Peptides, Cyclic; Spleen; Survival Analysis

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Humans; Infant; Leukocyte Count; Male; Recurrence; Ultrasonography; Urinalysis; Urinary Tract; Urinary Tract Infections

Topics: Amphotericin B; Antifungal Agents; Brain Neoplasms; Candida; Candida albicans; Candida glabrata; Candidiasis; Caspofungin; Child, Preschool; Drug Resistance, Fungal; Echinocandins; Humans; Immunocompromised Host; Lipopeptides; Male; Neuroectodermal Tumors; Neutropenia; Peptides, Cyclic; Time Factors

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Child, Preschool; Female; Fungemia; Humans; Immunocompromised Host; Microbial Sensitivity Tests; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

We report a leukemic patient with C. krusei fungemia who failed to respond to liposomal amphotericin B therapy alone. The addition of caspofungin eradicated infection and was well tolerated. Our report is the first to describe successful treatment of a patient with invasive C. krusei infection using this combination of antifungals. Combination therapy could be a useful treatment option for invasive candidosis, particularly when caused by more resistant species such as C. krusei.

Topics: Adult; Amphotericin B; Candida; Candidiasis; Caspofungin; Drug Therapy, Combination; Echinocandins; Fungemia; Humans; Leukemia; Lipopeptides; Male; Peptides, Cyclic; Treatment Outcome

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Drug Resistance, Fungal; Echinocandins; Female; Humans; Lipopeptides; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Peptides, Cyclic; Postoperative Complications; Recurrence; Reoperation

Candida glabrata is a rare cause of endophthalmitis after penetrating keratoplasty. Adequate therapy is still under discussion. With respect to severe complications and side effects of antifungal therapy, a substantial knowledge of sensitivity and resistance of the organism is necessary.. We report on a 26-year-old man with a hyperacute onset of the infection only 10 hours after surgery. A combined therapy for fluconazole and steroids administered over 3 months had shown no effect on intraocular infection.. After topical and intracameral application of amphotericin B in combination with topical prednisolone 3 months after the onset of the endophthalmitis, the infection disappeared within 14 days, and the graft remained clear for 2 months. No toxic effects were noticed.. In the case presented here, topical and intracameral application of amphotericin B was sufficient and safe in the therapy for C. glabrata endophthalmitis after penetrating keratoplasty. Although typically the intraocular infection is first noticed within the first 2 weeks, a hyperacute onset has to be considered.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Fungal; Glucocorticoids; Humans; Keratoplasty, Penetrating; Male; Postoperative Complications; Prednisolone

Caspofungin, an echinocandin, is approved for use in invasive candidiasis. Few cases of break-through candidal infections during caspofungin therapy have been reported and none have involved Candida parapsilosis. Here, we report a patient who developed multiple post-operative complications after pancreaticoduodenectomy for a pancreatic mass, including fungemia due to C. parapsilosis, while on caspofungin for treatment of Candida glabrata peritonitis. The fungemia resolved after a central venous catheter was removed and therapy was switched from caspofungin to amphotericin B lipid complex. Studies of C. parapsilosis susceptibility and the pharmacodynamics and drug interactions of caspofungin that may contribute to breakthrough fungemia are discussed.

Topics: Aged; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Catheters, Indwelling; Cross Infection; Drug Combinations; Drug Resistance, Fungal; Echinocandins; Fungemia; Humans; Lipopeptides; Male; Pancreaticoduodenectomy; Peptides, Cyclic; Phosphatidylcholines; Phosphatidylglycerols; Postoperative Complications

Topics: Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candidiasis; Cataract Extraction; Endophthalmitis; Eye Infections, Fungal; Humans; Male; Postoperative Complications

The interaction of posaconazole and amphotericin B was evaluated in concomitant treatment of Candida albicans systemic infections in immunocompetent mice by using four strains of C. albicans with different susceptibilities to fluconazole. Posaconazole and amphotericin B were each tested at four dose levels alone and in all possible combinations against each C. albicans strain. Survival curves of mice treated with combinations of posaconazole and amphotericin B were statistically compared with those of mice treated with the component monotherapies. Of the 64 total combinations evaluated against the C. albicans strains (16 combinations per strain), 20.3% were more effective in prolonging mouse survival than both of the monotherapies, 45.3% were more effective than one of the monotherapies, and 32.8% were similar to both monotherapies. No evidence of antagonism was observed between posaconazole and amphotericin B in this mouse model, consistent with in vitro results against the same strains.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Drug Interactions; Male; Mice; Survival Analysis; Triazoles

To identify potential risk factors associated with Candida infections and compare these risk factors between patients who both died and survived.. A group of patients with positive Candida spp. blood cultures admitted to a neonatal intensive care unit (NICU) in Costa Rica between January 1994 and December 1998. Cases were identified through a computerized search of the microbiology laboratory's database on blood cultures.. One hundred and ten newborns were identified. Sixty-six patients (60%) were male; 46 (62%) were preterm infants. Thirty-seven (34%) patients died. Twenty (54%) of them died within three days of the candidemia diagnosis and 17 had disseminated Candida infection on autopsy. Candida albicans and Candida tropicalis were isolated in 90% and 10% of blood cultures, respectively. Mean +/- SD (range) number of days from admission to NICU to the initial positive blood culture were 13.5 +/- 8.5 (1-30) days. Most patients had at least two positive blood cultures (range 1-8). Median (range) days for the sterilization of blood culture were four (1-25) days. Significant differences in survival were identified in patients with axillary-inguinal lesions, apnea and seizures.. Invasive fungal infections are frequent in NICU. Future case-control prospective studies should be carried out to confirm the findings from this report.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Costa Rica; Fluconazole; Flucytosine; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Retrospective Studies; Risk Factors

Drug delivery technology has brought additional benefits to pharmaceuticals such as reduction in dosing frequency and side effects, as well as the extension of patient life. To address this need, cochleates, a precipitate obtained as a result of the interaction between phosphatidylserine and calcium, have been developed and proved to have potential in encapsulating and delivering small molecule drugs. This chapter discusses the molecules that can be encapsulated in a cochleate system and describes in detail the methodology that can be used to encapsulate and characterize hydrophobic drugs such as amphotericin B, a potent antifungal agent. Some efficacy data in animal models infected with candidiasis or aspergillosis are described as well.

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Aspergillosis; Calcium; Candidiasis; Drug Compounding; Drug Delivery Systems; Freeze Fracturing; Humans; Hydrogels; Hydrogen-Ion Concentration; Lipid Bilayers; Liposomes; Mice; Phosphatidylserines

Polyene antibiotics (i.e., amphotericin B and nystatin) have been incorporated into lipid-based delivery systems to decrease their toxicity and enhance their therapeutic index, the most common being liposomes. This chapter describes the protocols for preparing liposomal amphotericin B and determining the efficacy and toxicity of the formulations in animals. Furthermore, methods for determining the pharmacokinetics and drug distribution after administration of amphotericin B in lipid-based delivery systems are discussed. Procedures for comparing the toxicity of different amphotericin B formulations in cell culture studies are also elucidated.

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Candidiasis; Cell Line; Drug Carriers; Liposomes; Mice; Nystatin; Rabbits

Candida spp. has been the leading microorganism isolated from the urine specimens of patients hospitalized at the Anesthesiology and Reanimation intensive care unit (ICU) of Dokuz Eylul University Hospital, Izmir, since 1998. This study was undertaken to investigate the clonal relationship of Candida urine isolates in order to find the mode of spread among the patients. Epidemiological surveillance of 38 Candida albicans, 15 Candida tropicalis and 12 Candida glabrata recovered from the urine specimens of patients who were hospitalized in the ICU between June 11, 2000 and October 15, 2001 was carried out by antifungal susceptibility testing and randomly amplified polymorphic DNA (RAPD) analysis. Two short primers [Cnd3 (5'-CCAGATGCAC-3') and Cnd4 (5'-ACGGTACACT-3')] were used for RAPD. None of the isolates had high minimal inhibitory concentration (MIC) values (>1 microg ml(-1)) against amphotericin B with MIC50 values of 0.5 microg ml(-1), 0.5 microg ml(-1) and 0.125 microg ml(-1) for C. albicans, C. tropicalis and C. glabrata isolates, respectively. However, three C. glabrata isolates were resistant and one C. albicans and five C. glabrata isolates were dose-dependent susceptible (D-DS) to fluconazole. Among C. albicans isolates 19 and 20 patterns were detected with primers Cnd3 and Cnd4, respectively. When primers Cnd3 and Cnd4 were evaluated together, three and four genotypes were identified for C. tropicalis and C. glabrata isolates, respectively. Our results suggest that the source of C. albicans isolates was mostly endogenous. It is difficult to interpret the mode of spread of C. tropicalis and C. glabrata urine isolates as we obtained insufficient banding patterns for these species.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; DNA Fingerprinting; DNA, Fungal; Drug Resistance, Fungal; Fluconazole; Genotype; Humans; Intensive Care Units; Microbial Sensitivity Tests; Molecular Epidemiology; Random Amplified Polymorphic DNA Technique; Turkey; Urine

In present study, we investigated the synergic effect of berberine against disseminated candidiasis caused by the pathogenic fungus, Candida albicans. Berberine inhibited the growth of C. albicans under in-vitro condition. The broth susceptibility revealed the synergic effect of berberine with amphotericin B (Amp B). To confirm these results under the in-vivo condition, the effect was examined in mice against disseminated candidiasis. Results showed mice that were given diluent (negative control), Amp B (0.5 mg/kg of body weight), or berberine (1 mg/kg of body weight) had mean survival times (MST) of approximately 12, 14, and 17 d, respectively. On the contrary, mice that were treated using a combination of the two agents at the same concentrations resulted in a MST value of 36 d, surviving at an average of 22 d longer than the mice group treated only with the Amp B. This MST value was almost same as MST value from the mice that were given four times the Amp B dose. These data indicate that the combination of Amp B and berberine could reduce approximately 75% of the Amp B dose, implying that berberine indeed has synergy with Amp B against the disseminated disease.

Topics: Amphotericin B; Animals; Berberine; Candidiasis; Drug Synergism; Female; Mice; Mice, Inbred BALB C

Endogenous Candida endophthalmitis is a rare disease with increasing frequency and poor prognosis.. The course of endogenous Candida endophthalmitis in 7 eyes of 5 patients (age 2 months to 76 years) was evaluated. Underlying general diseases were diagnosed as colon cancer, diverticulitis, pancreatic insufficiency (with subclavian catheter), ileus and diabetes mellitus. Diagnosis was based on the very typical ocular feature combined with a positive blood or vitreous culture. Intensive antimycotic drug therapy was initiated and pars plana vitrectomy performed as soon as possible.. The delay between onset of ocular symptoms and diagnosis amounted to one week and 2 months. In 3 eyes of 2 patients no vitrectomy could be done because of the very impaired state of health. These patients died of their general diseases one week and 2 months, respectively, later. During follow-up (4 weeks to 51 months) three eyes reached visual acuity of 5/10, 4/10 and 1/10. One eye reached 1/20 after additional surgery because of retinal detachment. In all vitrectomized eyes the diagnosis was substantiated by a positive culture of vitreous fluid. No recurrence of ocular inflammation was observed.. Early vitrectomy seems to be mandatory in each case which is suspected of Candida endophthalmitis. Only with this option it is possible to fix the diagnosis and initiate adequate therapy in due time in order to improve the original poor prognosis.

Topics: Aged; Amphotericin B; Anterior Chamber; Antifungal Agents; Candidiasis; Endophthalmitis; Female; Fungemia; Gentamicins; Humans; Infant, Newborn; Infant, Premature, Diseases; Injections; Male; Ophthalmic Solutions; Opportunistic Infections; Prednisone; Risk Factors; Treatment Outcome; Vitrectomy; Vitreous Body

We report a case of candidal liver abscesses and concomitant candidal cholecystitis in a diabetic patient, in whom differences were noted relative to those found in patients with hematologic malignancies. In our case, the proposed entry route of infection is ascending retrograde from the biliary tract. Bile and aspirated pus culture repeatedly tested positive, and blood negative, for Candida albicans and Candida glabrata. Cholecystitis was cured by percutaneous gallbladder drainage and amphotericin B therapy. The liver abscesses were successfully treated by a cumulative dosage of 750 mg amphotericin B. We conclude that in cases involving less immunocompromised patients and those without candidemia, a lower dosage of amphotericin B may be adequate in treating candidal liver abscesses.

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Cholecystitis; Humans; Liver Abscess; Liver Neoplasms; Male

Candida albicans is the most frequent cause of fungal keratitis in temperate regions. Caspofungin has potent activity against Candida spp. in a variety of clinical settings. Little is known, however, about its activity against fungal keratitis. We compared the efficacy of topical caspofungin with that of topical amphotericin B (AMB) in a rabbit model of experimental keratomycosis. Keratitis was induced with a standardized inoculum of Candida albicans (SC 5314) placed on the debrided cornea. Twenty-four hours after infection, animals were randomly assigned to treatment with 0.15% caspofungin, 0.5% caspofungin, 0.15% AMB, and a saline control (n = 12 rabbits in each group). For the first 12 h, treatment was repeated every 30 min and, after a 12-h pause, was resumed at hourly intervals for another 12 h. The animals were examined and killed 12 h after administration of the last dose. Treatment effects were evaluated by clinical assessment, fungal culture, and histopathology. Drug treatment significantly reduced corneal fungal recovery from 3.78 log10 CFU in saline-treated animals to 2.97, 1.76, and 1.18 log10 CFU in animals treated with 0.15% caspofungin, 0.5% caspofungin, and 0.15% AMB, respectively. By histopathology, the mean hyphal density was significantly lower in the corneas of treated animals than in those of the controls; there was no difference in hyphal densities between the different treatment groups. The depth of corneal invasion was not significantly reduced by the antifungal treatments. By clinical assessment, keratitis progressed in animals treated with saline, whereas disease progression was inhibited by all drug treatment regimens. In our rabbit model, 0.5% caspofungin was as effective as 0.15% AMB for the topical treatment of Candida keratitis. The potential clinical efficacy of caspofungin awaits further investigation.

Topics: Administration, Topical; Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Caspofungin; Disease Models, Animal; Echinocandins; Eye Infections, Fungal; Humans; Keratitis; Lipopeptides; Male; Peptides, Cyclic; Rabbits; Treatment Outcome

The efficacy and renal safety of amphotericin B lipid complex (ABLC) were assessed in >900 patients with candidiasis. Overall, a favorable clinical response (cured or improved) was observed in 61% of patients infected with Candida species only, in 62% of patients infected with C. albicans, and in 61% of patients infected with a non-albicans Candida species. Clinical responses were similar in patients infected with invasive C. albicans and non-albicans Candida species (63% and 62%, respectively). Similarly, response rates of 60% and 59% were observed in patients infected with noninvasive C. albicans and non-albicans Candida species, respectively. Compared with patients who received lower doses of ABLC, patients who required higher doses of ABLC because of more-virulent infections did not demonstrate significant renal impairment, as assessed by end-of-therapy changes in serum creatinine level from baseline (median, 0.1 mg/dL; range, -3.9 to 2.4 mg/dL), incidence of serum creatinine doubling (16%), and need for new dialysis (7%). These data indicate the safety and efficacy of ABLC in treating candidiasis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Drug Combinations; Female; Humans; Infant; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols; Registries; Treatment Outcome

Susceptibilities to amphotericin B and fluconazole of 628 clinical yeast strains collected from 22 hospitals in Taiwan were determined. A total of 53 isolates (8.4%) were resistant to fluconazole. Each hospital had different resistance rate to fluconazole ranging from 0% to 24%. None of the 186 isolates from eight of the 22 hospitals was resistant to fluconazole. In contrast, isolates from nine of the remaining 14 hospitals had greater than 10% resistance rate to fluconazole. Consistently, 88.9% (8/9) fluconazole-resistant C. albicans isolates were from hospitals having a high resistance rate to fluconazole. The prevalence of various Candida spp. in each hospital was different. A positive association was found between the prevalence of C. tropicalis and the resistance rate to fluconazole for individual hospitals. Although only three isolates (0.5%) were resistant to amphotericin B, a co-resistance to both amphotericin B and fluconazole was observed, which highlights the emerging problem of drug resistance.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida tropicalis; Candidiasis; Drug Resistance, Microbial; Fluconazole; Hospitals; Humans; Microbial Sensitivity Tests; Prevalence; Taiwan

Aspiration of oropharyngeal bacteria and fungi is occasionally suspected in patients with pneumonia. A patient with oral carcinoma underwent chemoradioimmunotherapy and, about 4 weeks from the start of the therapy, the patient suffered from severe oral mucositis induced by chemoradiotherapy, and candidal pneumonia was subsequently induced. The candidal pneumonia was insufficiently improved by potent antifungal drugs, taking a lethal course. Randomly amplified polymorphic DNA analysis and DNA sequence examination of strains isolated from the oral cavity 1 week before the onset of pneumonia and autopsied lung revealed the identity of both strains as Candida albicans, and the DNA analysis supported aspiration of oral Candida. These results indicate that the pathogen of the pneumonia, C. albicans, was aspirated from the oral cavity and that oral Candida is easily aspirated and becomes the pathogen of pneumonia.

Topics: Aerosols; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Base Sequence; Candida albicans; Candidiasis; Candidiasis, Oral; Carcinoma, Squamous Cell; DNA, Fungal; Fatal Outcome; Female; Fluconazole; Humans; Miconazole; Mouth Neoplasms; Pneumonia, Aspiration; Random Amplified Polymorphic DNA Technique

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Chorioretinitis; Eye Infections, Fungal; Fluconazole; Fluorescein Angiography; Humans; Male; Visual Acuity

We investigated the in vitro activity of caspofungin compared to amphotericin B, fluconazole, and itraconazole against clinical strains of Candida spp. (n =239). Antifungal susceptibility tests were done in accordance with NCCLS M27-A2 microdilution method and the results were read after 24 and 48 h. In general, 24 h MIC readings were similar to those at 48 h for most isolates and all antifungal agents. Caspofungin was active against all species tested. Caspofungin MICs of Candida parapsilosis were slightly higher than those for other Candida spp. Caspofungin MIC (microg/ml) ranges at 24 h for C. albicans, C. glabrata, C tropicalis, C. parapsilosis, C kefyr, C krusei, C. lusitaniae, C. norvegensis, C. guilliermondii and C. lipolytica were 0.06-2, 0.125-2, 0.125-2, 1-4, 0.125-2, 1-2, 0.5-2, 0.5-1, 0.5-2 and 1-2, respectively. Eagle (paradoxical) effect was observed in 31 and 8% of the isolates at highest concentrations of caspofungin and itraconazole, respectively. The activity of caspofungin against fluconazole- and/or itraconazole-resistant isolates was similar to that detected for the susceptible ones. We conclude that caspofungin appears as a promising antifungal agent with enhanced activity against Candida, including the azole-resistant strains.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Echinocandins; Fluconazole; Hospitals, University; Itraconazole; Lipopeptides; Microbial Sensitivity Tests; Peptides, Cyclic; Turkey

Amphotericin B is the primary antifungal agent used for candida sepsis in neonates. Breakthrough candidemia was not reported in neonates during either amphotericin B or liposomal amphotericin B (AmBisome) treatment. We describe a case of a premature infant with congenital cutaneous candida infection, who had two episodes of breakthrough infection, from Candida albicans and Candida parapsilosis, while he was treated with amphotericin B and AmBisome, respectively. We discuss the pathogenesis of breakthrough infections, and the relevance of antifungal resistance and sensitivities testing.

Topics: Amphotericin B; Antifungal Agents; Bacteremia; Candidiasis; Candidiasis, Cutaneous; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Microbial Sensitivity Tests; Pregnancy

We report two patients, who developed dilated cardiomyopathy and subsequent congestive heart failure after treatment with amphotericin B (AmB). The echocardiographic findings and the symptoms of heart failure resolved after the discontinuation of the drug. The clinical data from our cases and two similar cases reported in the literature suggest that the presence of other factors predisposing to cardiac dysfunction may facilitate the occurrence of this rare side effect.

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Cardiomyopathies; Female; Female Urogenital Diseases; Fever; Humans; Injections, Intravenous; Male; Male Urogenital Diseases; Middle Aged; Withholding Treatment

Over the last few decades, the incidence of invasive candidal infections in neonatal intensive care units has increased dramatically. Various complications, such as arthritis, endocarditis, meningitis, and endophthalmitis, have been reviewed. We present the case of a premature infant with systemic candidemia. Arthritis was discovered 6 months after completion of amphotericin B therapy, and was successfully treated with oral fluconazole for 6 weeks. We conclude that long-term follow-up is particularly important in patients with treated candidemia. To prevent complications, prolonged treatment with high-dose amphotericin B is suggested for systemic fungal infection, and oral fluconazole is an effective alternative for candidal arthritis.

Topics: Amphotericin B; Antifungal Agents; Arthritis; Candidiasis; Diabetes, Gestational; Female; Fluconazole; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Knee; Magnetic Resonance Imaging; Male; Pregnancy; Radiography; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Critical Illness; Fluconazole; Humans; Male; Middle Aged

In the past few years, we have detected in the United Kingdom and in the United States several isolates of Candida glabrata that grew poorly unless bile was available. Cholesterol, a component of bile, stimulated equivalent growth of the bile-dependent isolates. The bile-dependent C. glabrata isolates appeared resistant to amphotericin B, but their resistance to fluconazole was unclear. These results demonstrate that occasional isolates of C. glabrata require cholesterol to grow, they may not be detected in specimens set up on standard primary plating media, and they may be difficult to eradicate in patients with antifungal agents directed against ergosterol and its synthetic pathway.

Topics: Aged; Amphotericin B; Antifungal Agents; Bile; Candida glabrata; Candidiasis; Cholesterol; Culture Media; Drug Resistance, Fungal; Humans; Male; Microbial Sensitivity Tests

To present a series of neonates with renal fungus balls diagnosed by ultrasonography, urine culture and/or by the detection of Candida pseudomycelium in urine.. We revised the clinical records of neonates for whom the diagnosis of renal fungus ball was established by ultrasound and laboratory studies; these patients had been hospitalized at the National Institute of Pediatrics in Mexico between January 1st, 1999 and December 31st, 2002.. During the study period, 9 neonates were diagnosed with renal fungus ball. In 7 cases, the ethiologic agent was Candida albicans; whereas it was C. tropicalis in one case and C. parapsilosisin the other. Urine culture was positive (> or =10,000 UFC/ml) in 8 cases, whereas the fungal density was only 2400 UFC/ml in the last sample. Pseudohyphae were present in all cases and ultrasonography showed fungus ball in every case. All patients received a single antifungal drug, either amphotericin B or fluconazole. All the patients recovered and none of them required surgical treatment. Control postreatment by ultrasound studies showed that the fungus balls had disappeared in every case.. The diagnosis of Candida renal fungus balls based on the ultrasound study and urine culture is also substantiated by the detection of pseudomycelium in the centrifugation pellet of urine samples, which is a fast diagnostic method. This approach permitted an early diagnosis and treatment of Candida renal fungus balls.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Female; Fluconazole; Humans; Infant, Newborn; Male; Microbial Sensitivity Tests; Mycelium; Ultrasonography; Urinary Bladder; Urinary Tract Infections; Urine

The effects of caspofungin combined with amphotericin B were investigated with Candida glabrata. Although in vitro experiments showed an indifferent interaction, the combination regimen was the only therapeutic approach yielding organ sterilization in a murine candidemia model.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Colony Count, Microbial; Drug Therapy, Combination; Echinocandins; Fungemia; Lipopeptides; Male; Mice; Microbial Sensitivity Tests; Peptides, Cyclic; Treatment Outcome

Minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) were determined for 38 oils of plant origin against Candida albicans. Four strains including one standard strain were used in this study. The antifungal agents, Fluconazole and Amphotericin B were used as positive controls. The standard strain (ATCC10231) used in this study was found to be highly resistant to Fluconazole: 3000 microg ml(-1) of Fluconazole was required to inhibit the growth of this strain partially, and complete inhibition could not be achieved. Other Candida strains were sensitive to 5 microg ml(-1) of Fluconazole. All the strains used were sensitive to Amphotericin B. Of the 38 oils tested, 23 were found effective and fifteen were ineffective. Based on their MFCs, effective oils were categorized into three categories. Seven oils, which exerted fungicidal effect at less than 0.15% concentration of oils, were grouped into the most effective class. The oils exhibiting MFCs in the range of 0.16-1.5% concentration were considered moderately effective. Nine oils, which required more than 1.5% concentration, were regarded as less effective. The Fluconazole-resistant strain (MTCC 227) was sensitive to at least 23 of the plant oils. Results of this study indicate that oils of plant origin may find use as potential anti-Candida agents.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Fluconazole; Humans; Microbial Sensitivity Tests; Plant Oils

A preterm infant younger than 3 months developed a disseminated fluconazole-resistant Candida albicans infection that was treated with liposomal amphotericin B for 52 days, followed by the combination of intravenous voriconazole and liposomal amphotericin B for an additional 19 days. The infant received concomitant phenobarbital throughout the hospital stay. The infection resolved after addition of voriconazole to the treatment regimen. Intravenous voriconazole was begun at a high dosage, 6 mg/kg every 12 hours, for anticipated developmental and drug-induced changes in volume of distribution and clearance. On day 4 of therapy, serum concentrations of voriconazole were 3.27 microg/ml immediately after infusion and 0.33 microg/ml 6 hours after infusion. These levels were significantly lower than those achieved in adult pharmacokinetic and safety studies. After the infant's dosage was increased to 6 mg/kg every 8 hours, serum concentrations were 5.33 microg/ml 30 minutes after infusion and 2.67 microg/ml 6 hours after infusion. These levels were similar to those observed in adults. Intravenous voriconazole 6 mg/kg every 8 hours was administered safely, with concomitant phenobarbital therapy, in this preterm infant with developmentally diminished renal function.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Humans; Infant, Newborn; Infant, Premature; Infusions, Intravenous; Pyrimidines; Triazoles; Voriconazole

The incidence of endocarditis produced by the so-called "opportunists" as a complication of prosthetic valve surgery is progressively increasing in frequency and gradually transforming the clinical picture habitually associated with this disease. Candida endocarditis is an unusual but severe complication caused by Candida albicans or other fungal species. This case and a review of the literature indicate that Candida endocarditis treated with amphotericin B and prosthetic valve replacement may recur months after treatment, and that late recurrent Candida endocarditis, which is difficult to diagnose and treat, may be best prevented by lifelong antifungal suppressive therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Bioprosthesis; Candida tropicalis; Candidiasis; Endocarditis; Female; Heart Valve Prosthesis; Humans; Mitral Valve; Review Literature as Topic

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Carcinoma, Non-Small-Cell Lung; Catheters, Indwelling; Fatal Outcome; Humans; Liposomes; Lung Neoplasms; Male; Osteomyelitis; Recurrence; Thoracic Surgical Procedures; Thoracic Vertebrae; Treatment Outcome

In the present study the effect of the indole alkaloid ibogaine on the in vitro lipolytic activity and adherence to epithelial cells of Candida albicans was investigated. The substance was administered intraperitoneally at a dose of 5 mg kg(-1) day(-1) in mice with disseminated and gastrointestinal C. albicans infections. Ibogaine significantly decreased the rate of mortality and the number of C. albicans c.f.u. recovered from the kidney, liver and spleen. Ibogaine interfered with the early stages of both disseminated and gastrointestinal C. albicans infections but did not reduce the number of C. albicans c.f.u. in the organs at the late phase of infections. The development of a specific immune response was not influenced by ibogaine, since the delayed-type hypersensitivity reaction to C. albicans and the production of interferon (IFN)-gamma were similar in control and ibogaine-treated mice. The combined use of amphotericin B plus ibogaine in the treatment of mice with gastrointestinal infection reduced organ colonization more strongly than each substance alone.

Topics: Adhesiveness; Amphotericin B; Animals; Antifungal Agents; Brain; Candida albicans; Candidiasis; Drug Therapy, Combination; Enzyme Inhibitors; Female; Gastrointestinal Diseases; Hypersensitivity, Delayed; Ibogaine; Injections, Intraperitoneal; Kidney; Lipase; Liver; Male; Mice; Mice, Inbred BALB C; Spleen

Candida endophthalmitis represents the most serious ocular complication of candidemia. The pharmacokinetics and pharmacodynamics of fluconazole, amphotericin B, and flucytosine are fairly well established in endophthalmitis therapy. There remains a paucity of clinical data regarding the utility of new antimycotic agents in the treatment of fungal chorioretinitis and endophthalmitis. We report a case of clinical failure of caspofungin in the management of Candida albicans endophthalmitis associated with poor vitreous penetration.

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Drug Combinations; Echinocandins; Endophthalmitis; Humans; Lipopeptides; Male; Peptides, Cyclic; Phosphatidylcholines; Phosphatidylglycerols; Treatment Failure

To report an outbreak of Pichia anomala fungemia that occurred in a Brazilian pediatric intensive care unit (ICU) from October 2002 to January 2004.. Unmatched case-control study.. We randomly selected four control-patients for each case-patient from a list of all patients admitted to the ICU for at least 48 hours during the outbreak. A second control group was composed of all consecutive patients with nosocomial candidemia in the ICU during the outbreak. An environmental study was performed, and genetic relatedness among the clinical isolates was characterized by randomly amplified polymorphic DNA assay.. During the study period, 1,046 children were admitted to the pediatric ICU, 17 of whom developed P. anomala fungemia (attack rate, 1.6%). The median age was 1.1 years, and the main underlying conditions were congenital malformations (35.3%) and neoplastic diseases (11.8%). The overall mortality rate was 41.2%. Two patients received no antifungal treatment; all of the others were treated with amphotericin B. On multivariate analysis, only the presence of a central venous catheter was significantly associated with P. anomala fungemia. The yeast was not found on healthcare workers' hands or in the environment. Molecular studies showed that the outbreak was caused by a single strain. The distribution of risk factors was similar between patients with P. anomala fungemia and control-patients with candidemia.. This study highlights the importance of P. anomala as an emerging nosocomial fungal pathogen. Patients with P. anomala fungemia seem to have risk factors in common with those who have candidemia.

Topics: Age Distribution; Amphotericin B; Antifungal Agents; Brazil; Candidiasis; Case-Control Studies; Catheterization, Central Venous; Communicable Diseases, Emerging; Cross Infection; Disease Outbreaks; DNA, Fungal; Female; Fungemia; Hospital Mortality; Humans; Infant; Intensive Care Units, Pediatric; Male; Microbial Sensitivity Tests; Multivariate Analysis; Pichia; Random Amplified Polymorphic DNA Technique; Risk Factors; Seasons

The strategy of combining antifungal drugs in a treatment regimen may improve the outcome of invasive candidiasis. Using a well-validated pharmacodynamic murine model of invasive candidiasis, we defined the effect of the combination of amphotericin B deoxycholate (AmB) and 5-fluorocytosine (5FC) by use of the Greco model of drug interaction. The combination was additive, meaning that the experimental effect did not deviate in a statistically significant manner from the null reference model (or additive surface) of the combined effect. From a clinical perspective, the addition of 5FC to a regimen of AmB may enable the near-maximum effect to be reached in circumstances in which the administration of a given dose of AmB alone produces a submaximum effect but an increase in the dose is not possible, because of dose-related toxicity. Our methods provide a way in which some of the complex issues surrounding antifungal combination treatment can be addressed.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Drug Therapy, Combination; Flucytosine; Male; Mice; Microbial Sensitivity Tests; Models, Biological

To compare the activity of aminocandin (IP960), a new echinocandin with broad-spectrum in vitro activity against Aspergillus and Candida spp., with that of amphotericin B and fluconazole in a temporarily immunocompromised murine model of disseminated candidiasis.. Mice were rendered neutropenic with cyclophosphamide and infected intravenously 3 days later with a fluconazole-resistant Candida tropicalis strain. Mice were treated with intraperitoneal amphotericin B (5 mg/kg/dose), oral fluconazole (50 mg/kg/dose), intravenous aminocandin (0.1--5 mg/kg/dose) or solvent control for 9 days. Mice were observed for survival and survivors were sacrificed 11 days post-infection. Kidneys, liver, brain and lungs were removed for semi-quantitative culture.. Control mice had 90--100% mortality. After infection with C. tropicalis, aminocandin 2.5 and 5 mg/kg/day and amphotericin B yielded 80% survival; aminocandin 1 mg/kg/day yielded 70% survival; aminocandin 0.25 and 0.1 mg/kg/day yielded 30% and 20% survival, respectively; and fluconazole 50 mg/kg/day and control regimens yielded 10% and 0--10% survival, respectively. Aminocandin 2.5 and 5.0 mg/kg/day and amphotericin B were superior in reducing mortality compared with aminocandin 0.25 and 0.1 mg/kg/day, fluconazole and controls (P<0.047). The only regimen to reduce organ burdens below detectable levels was amphotericin B, which cleared 40% of mice. All organ burdens in the aminocandin 1.0, 2.5 and 5.0 mg/kg/day and amphotericin B regimens were significantly lower than other groups (P<0.02).. The data demonstrate that aminocandin at doses of >or=1.0 mg/kg/day is as effective as amphotericin B at improving survival and reducing organ burdens in this murine model of disseminated C. tropicalis.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida tropicalis; Candidiasis; Cyclophosphamide; Disease Models, Animal; Drug Resistance, Fungal; Fluconazole; Immunocompromised Host; Lipopeptides; Lipoproteins; Male; Mice; Mice, Inbred Strains; Neutropenia; Survival Rate; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Catheterization, Central Venous; Catheters, Indwelling; Fungemia; Humans; Infant; Liposomes

For the first time in the literature to date, we report 2 cases of transplantation of yeast-infected cardiac allografts. In both cases, endocardial vegetations were observed before graft implantation. Microbiologic samples grew yeasts: Rhodotorula glutinis was found close to the left atrial appendage in the first case and Candida parapsilosis was identified in a vegetation located at the base of the tricuspid valve in the second case. We discuss the possible routes of donor organ infection and management of these 2 unusual cases.

Topics: Adult; Amphotericin B; Candida albicans; Candidiasis; Fluconazole; Follow-Up Studies; Graft Survival; Heart Failure; Heart Transplantation; Humans; Male; Middle Aged; Mycoses; Risk Assessment; Severity of Illness Index; Tissue Donors; Transplantation, Homologous; Transplants; Treatment Outcome; Yeasts

In a randomized, comparative, clinical trial, caspofungin was found to be as effective as amphotericin B deoxycholate (ampho B) for treating candidemia (favorable outcomes in 71.7% and 62.8% of patients, respectively) and exhibited a generally better safety profile, particularly with respect to impaired renal function (IRF) (P = 0.02).. The goal of this study was to examine whether cost savings generated from the reduced rates of IRF observed in the clinical trial would be enough to offset the higher acquisition cost of caspofungin relative to ampho B.. We developed an economic model in which 100 hypothetical patients with candidemia were treated with caspofungin or ampho B. Rates of IRF and duration of drug therapy were taken from the clinical trial. Information on the cost of treating IRF was obtained through a search of MEDLINE using the terms amphotericin and cost, amphotericin and resource, amphotericin and hospital, and amphotericin and toxicity; and the medical subject headings kidney failure, acute/drug therapy; kidney failure, acute/epidemiology; kidney failure, acute/etiology; kidney/drug effects; cost of illness; costs and cost analysis; kidney failure, acute, and economics; and kidney failure, acute/economics. In addition, the Web site was searched for relevant references, and the Merck publication alert system was used. Antifungal drug costs were estimated using data from IMS Health. Costs were reported in year-2003 US dollars.. In the base case, the model projected that using caspofungin instead of ampho B would result in substantially lower treatment costs for IRF, which would more than offset the higher drug acquisition cost (cost-offset percentage, 122%), leading to a net mean savings of 758.60 US dollars per patient. These results were not very sensitive to the difference in daily drug cost, but were sensitive to the mean cost attributable to treating IRF. As that varied, the cost-offset percentage varied from 61% (substantial cost offset) to 183% (cost savings).. The results of this economic model suggest that, based only on differences in drug acquisition cost and renal toxicity, the use of caspofungin instead of ampho B in patients with candidemia may be a cost-saving strategy from the perspective of a hospital.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Cost-Benefit Analysis; Echinocandins; Economics, Pharmaceutical; Female; Humans; Lipopeptides; Male; Middle Aged; Models, Economic; Peptides, Cyclic; Randomized Controlled Trials as Topic; Renal Insufficiency

Although voriconazole shows an advantageous microbiological and pharmacological profile with respect to amphotericin B and other antifungals, the cumulative experience with the use of voriconazole in patients intolerant to other antifungals or with refractory invasive fungal infections is still limited. We performed a retrospective analysis of the charts of 48 patients in 26 Spanish hospitals who were diagnosed with invasive fungal infections due to filamentous fungi or yeasts and had received voriconazole (between 1999 and 2002) as part of a compassionate use program for a mean of 59.2 days (range 1-748 days). The favorable response rate in patients with invasive, refractory aspergillosis who were treated exclusively with voriconazole was 8/12 (66%). This response rate increased to 10/12 (83%) when two other cases treated with a combination of voriconazole plus caspofungin were included. In patients with invasive candidiasis the response rate was 66% (6/9). A favorable response was achieved in 12/17 (70%) patients with invasive fungal infections due to other difficult to treat fungi (Scedosporium spp., Fusarium spp., Blastoschizomyces spp.). The tolerability and safety profile of voriconazole was good; only four patients required discontinuation of treatment due to side effects. Voriconazole is a well-tolerated, effective antifungal for the treatment of patients with refractory invasive fungal infections due to Aspergillus spp., Candida spp. and fungi resistant or refractory to other treatments.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Child; Child, Preschool; Drug Resistance, Fungal; Female; Humans; Male; Middle Aged; Mycoses; Pyrimidines; Retrospective Studies; Spain; Treatment Outcome; Triazoles; Voriconazole

To evaluate the species distribution and antifungal susceptibility of Candida isolates in a tertiary institution in Israel, all consecutive isolates of Candida spp. recovered from blood during the last 2 years were studied. The isolates were identified by the germ tube test and the API ID 32C test (bioMérieux, Marcy l'Etoile, France). MICs of antifungal agents were determined by the E test. Candida albicans was the most commonly isolated species, accounting for 44% (63/142) of the isolates, followed by Candida tropicalis (25%; 35/142), Candida parapsilosis (20%; 29/142), Candida glabrata (10%; 14/142), and Candida krusei (0.7%; 1/142). All isolates were sensitive to amphotericin B and voriconazole. Resistance to fluconazole (using a high MIC of >/=256 microg/ml) was found in 1.6% of C. albicans isolates, in 3.4% of C. parapsilosis isolates, and in 21.4% of C. glabrata isolates. Resistance to itraconazole was detected in 3.2% of C. albicans isolates, in 2.9% of C. tropicalis isolates, in 3.4% of C. parapsilosis isolates, and in 93% of C. glabrata isolates. Disparities in species distribution and antifungal susceptibility of Candida isolates from the institute studied versus Candida isolates from other centers and countries are described. The findings emphasize the need for continuous surveillance and further clinical investigational studies.

Topics: Academic Medical Centers; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candida tropicalis; Candidiasis; Drug Resistance, Fungal; Fluconazole; Fungemia; Humans; Israel; Itraconazole; Pyrimidines; Species Specificity; Triazoles; Voriconazole

Molecular epidemiology revealed 5 distinct clades among clinical isolates of Candida albicans, using DNA fingerprinting with the complex Ca3 probe. Certain clades were found to be highly enriched in particular geographical areas (e.g., clade E in Europe and clade SA in South Africa, whereas clade II is completely absent in the southwest United States). From fingerprinting data, it is concluded that little interclade recombination takes place, and therefore, it would not be unusual to expect clade-specific phenotypic characteristics. The first clade-related phenotypic difference was found with 5-flucytosine resistance being almost exclusively restricted to clade I. When in vitro antifungal susceptibility testing revealed 8.4% of South African oral yeast isolates to be naturally resistant to amphotericin B, it was decided to investigate a possible clade relationship for this relatively high resistance. Thirty-eight amphotericin B-resistant C. albicans isolates were fingerprinted, and a mixed dendrogram was constructed, including previously fingerprinted isolates of known clade affiliation. With the exception of clade III, resistant isolates occurred in all clades (clade I=3; clade II=3; clade NG=3; and clade SA=29), except clade III. However, the higher number of resistant isolates that clustered in clade SA was statistically significant (P

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; DNA Fingerprinting; DNA, Fungal; Drug Resistance, Fungal; Humans; South Africa

We present a full-term female infant with congenital candidiasis characterized by extensive vesicular and pustular skin lesions associated with pneumonia and severe respiratory distress that appeared during the first hours after birth. The patient was born by cesarean section with no history of rupture of membranes. The mother had a vaginal discharge 3 weeks before delivery. The diagnosis was made by culture of pustular fluid, which grew Candida albicans. Systemic cultures were negative. The infant required a very brief course of conventional mechanical ventilation in spite of impressive and extensive lung infiltrates on the chest radiograph. She made a very quick clinical recovery although it is remarkable that antifungal treatment with amphotericin B was begun very late in her clinical course at the time when she was showing obvious signs of major improvement. Current management guidelines strongly recommend specific therapy for infants with invasive congenital candidiasis or with burn-like extensive dermatitis even without lung involvement. We are not suggesting any change in these recommendations; however, at least in our patient, when amphotericin B was started, she was clearly recovering; it seems possible that her disease although extensive might have experienced an unusual spontaneous regression. This case can provide further insights into this unusual neonatal infection.

Topics: Amphotericin B; Candidiasis; Candidiasis, Cutaneous; Female; Humans; Infant, Newborn; Lung Diseases, Fungal; Pneumonia; Remission, Spontaneous

To review our experience of caspofungin in the treatment of persistent candidemia in the neonatal intensive care unit.. This was a retrospective chart review on 13 infants in whom caspofungin was added to conventional antifungals (amphotericin B and/or fluconazole or flucytosine) for the treatment of refractory candidemia.. A total of 12 infants were preterm (gestational age, 24 to 28 weeks) and one was term; the median birth weight was 800 g (range, 530 to 5600 g). Candidemia (Candida albicans in five, C. parapsilosis in six, C. albicans and C. parapsilosis in one and C. tropicalis in one) persisted despite 6 to 30 days of conventional antifungal therapy. After the addition of caspofungin, sterilization of blood cultures was achieved in 11 infants at the median time of 3 days (range, 1 to 21 days). Adverse events included thrombophlebitis (one patient), hypokalemia (two patients) and elevation of liver enzymes (four patients). Three infants had a second episode of candidemia and seven patients died.. Caspofungin may be an efficacious addition for treatment of candidemia refractory to conventional antifungal therapy. This drug should be further investigated in neonates.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Drug Therapy, Combination; Echinocandins; Female; Fluconazole; Flucytosine; Fungemia; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Intensive Care, Neonatal; Lipopeptides; Male; Peptides, Cyclic; Retrospective Studies

Candidal vertebra osteomyelitis is a rare condition which occurs primarily in immunocompromised patients. We report a 14-year-old girl with factor X deficiency who developed candida vertebra osteomyelitis during home therapy. The microorganism was probably from a contaminated peripheral cannula used for infusion of factor concentrate. This is the first such case in bleeding disorders to our knowledge.

Topics: Adolescent; Amphotericin B; Candidiasis; Factor X Deficiency; Female; Humans; Liposomes; Lumbar Vertebrae; Magnetic Resonance Imaging; Osteomyelitis; Treatment Outcome

Systemic maternal-fetal Candida albicans infections are uncommon diseases with a poor outcome. An associated cerebromeningeal infection increases morbidity. We present a case of neuromeningeal candidiasis following systemic neonatal infection in a premature infant. Management and therapeutic difficulties are outlined.. The patient was a male infant born preterm at 30 weeks gestation. During his first week of life, he developed a systemic infection with an associated symptomatic hydrocephalus. Systemic candidaisis with neuromeningeal complication was diagnosed five weeks later. Despite treatment including cerebrospinal fluid (CSF) shunting and antimycotic medications (flucytosin and amphotericin B), the candidal infection did not resolve. Infectious and mechanical complications of the CSF drainage were treated by several surgical interventions during the following months. At 10 months of life, there was clinical and laboratory evidence of active persistent neuromeningeal candidaisis. Finally, candidal infection was eradicated with intravenous administration of fluconazole. After five year follow-up, the intellectual and psychological status of the patient was quite satisfactory, and no neurological deficits were found on clinical examination.. Management of neuromeningeal candidaisis in premature infants is a challenging task particularly because of delayed diagnosis. Candida infection should routinely be suspected in cases of systemic infection with neurological impairment in premature infants. Fluconazole may constitute an efficient therapeutic option.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Drug Therapy, Combination; Flucytosine; Humans; Hydrocephalus; Infant, Newborn; Infant, Premature; Magnetic Resonance Imaging; Male; Meningitis, Bacterial; Radiography

We compared the efficacies of amphotericin B, fluconazole, flucytosine, and micafungin in a systemic murine infection by three isolates of Candida glabrata. Amphotericin B showed the best results, although none of the drugs dramatically reduced mortality or tissue burden in liver or spleen.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida glabrata; Candidiasis; Echinocandins; Fluconazole; Flucytosine; Lipopeptides; Lipoproteins; Male; Micafungin; Mice; Microbial Sensitivity Tests; Peptides, Cyclic

While Candida albicans remains the most common Candida isolate, Candida glabrata accounts for approximately 15 to 20% of all Candida infections in the United States. In this study we used immunosuppressed mice infected with C. glabrata to investigate the efficacy of liposomal amphotericin B alone or in combination with the echinocandin caspofungin or micafungin. For monotherapy, mice were given six daily doses of liposomal amphotericin B (3 to 20 mg/kg of body weight), caspofungin (1 to 5 mg/kg), or micafungin (2.5 to 10 mg/kg). With concomitant therapy, mice received liposomal amphotericin B (7.5 mg/kg) in addition to caspofungin (2.5 mg/kg) or micafungin (2.5 mg/kg) for 6 days. For sequential therapy, liposomal amphotericin B was administered on days 1 to 3 and caspofungin or micafungin was given on days 4 to 6; conversely, caspofungin or micafungin was administered on days 1 to 3 and liposomal amphotericin B was given on days 4 to 6. Efficacy was based on the number of CFU per gram of kidney 21 days postchallenge. Monotherapy with liposomal amphotericin B (7.5 to 20 mg/kg) was significantly more effective than no drug treatment (control group) (P < 0.05) and demonstrated a dose-dependent response, with 20 mg/kg lowering the CFU/g from 6.3 to 4.2 (significantly different from the value for the control group [P < 0.001]). Monotherapy with all echinocandin doses lowered the CFU/g from 6.0 to 6.4 to 2.7 to 3.3 (significantly different from the value for the control group [P < 0.001]) with no dose-dependent response. Complete clearance of infection could be achieved only when liposomal amphotericin B was given either concomitantly with caspofungin or micafungin or if liposomal amphotericin B was given sequentially with caspofungin. In conclusion, the combination of liposomal amphotericin B with an echinocandin markedly improved the therapeutic outcome in murine C. glabrata systemic infection.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candidiasis; Caspofungin; Disease Models, Animal; Drug Therapy, Combination; Echinocandins; Immunocompromised Host; Lipopeptides; Lipoproteins; Liposomes; Micafungin; Mice; Peptides, Cyclic

Penetrating keratoplasty carries an infectious risk. Its requirement for topical corticosteroid therapy facilitates fungal growth with resulting keratitis. Although progression of fungal keratitis to intraocular infection is uncommon, endophthalmitis resulting from keratitis usually has a poor visual prognosis. Fungal infection under these circumstances remains a diagnostic and therapeutic challenge. We report a complicated case of recurrent fungal keratitis with endophthalmitis following a contaminated penetrating keratoplasty that ultimately was controlled with a new treatment modality. Intrastromal corneal injections combined with intravitreal injection of amphotericin B led to the eradication of the corneal fungal plaques and the intraocular infection. Intrastromal corneal injections of amphotericin B may offer a less invasive, in-office alternative to repeat penetrating keratoplasty.

Topics: Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Corneal Stroma; Corneal Ulcer; Disease Transmission, Infectious; Endophthalmitis; Eye Infections, Fungal; Female; Humans; Injections; Keratoplasty, Penetrating; Recurrence; Tissue Donors; Vitreous Body

Fungal sepsis is becoming more frequent in neonatal intensive care units (NICU) and has a high mortality rate due to the invasive nature of the disease and to the insufficiency of low doses and high incidence of renal problems with effective doses of amphotericin B. New generation lipid formulated amphotericin B preparations may be more efficient because they are less toxic to be applied in target doses. However, there is limited experience in neonates and preterm infants.. The charts of 917 patients admitted to NICU between 2001 and 2003 were reviewed and the data of 21 patients with systemic Candida infection, requiring different amphotericin B therapy, were analyzed.. Infants with fungal septicemia were treated with amphotericin B lipid complex (Abelcet)(n = 10) and liposomal amphotericin B (AmBisome)(n = 9) for a mean duration of 21 and 18 days. The mean gestational age of the patients was 30.9 +/- 4.2 weeks and mean birth weight was 1536 +/- 714 g. Two patients in the Abelcet group and one patient in the AmBisome group died during therapy. Fungal eradication was achieved in 16 surviving infants and mean eradication time was 8.1 +/- 2.6 days and mean duration of therapy was 19.2 +/- 4.1 days. Mortality rates related to treatment failure were similar being 20% in the Abelcet group and 11% in the AmBisome group. No patient showed severe side-effects from the antifungal therapy; the incidence of minimal side-effects were similar in both groups and they were elevated serum transaminase levels in six patients, increased serum creatinine in one patient and hypokalemia in one patient.. Both preparations have the same benefits for the treatment of neonatal fungal sepsis and they can be used safely in neonates including very low birth weight infants. However, the clinician must keep in mind the cost of treatment.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Drug Combinations; Fungemia; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Phosphatidylcholines; Phosphatidylglycerols; Retrospective Studies; Treatment Outcome

Mortality from invasive candidiasis is high. Low culture sensitivity and treatment delay contribute to increased mortality, but nonselective early therapy may result in excess costs and drug resistance.. To determine the cost-effectiveness of anti-Candida strategies for high-risk patients in the intensive care unit (ICU).. Cost-effectiveness decision model.. Published data to 10 May 2005, identified from MEDLINE and Cochrane Library searches, ICU databases, expert estimates, and actual hospital costs.. Patients in the ICU with suspected infection who have not responded to antibacterial therapy.. Lifetime.. Societal.. Fluconazole, caspofungin, amphotericin B, or lipid formulation of amphotericin B given as either empirical or culture-based therapy and no anti-Candida therapy.. Incremental life expectancy and incremental cost per discounted life-year (DLY) saved.. Ten percent of the target population will have invasive candidiasis. Empirical caspofungin therapy is the most effective strategy but is expensive (295,115 dollars per DLY saved). Empirical fluconazole therapy is the most reasonable strategy (12,593 dollars per DLY saved) and decreases mortality from 44.0% to 30.4% in patients with invasive candidiasis and from 22.4% to 21.0% in the overall target cohort.. Empirical fluconazole therapy is reasonable for likelihoods of invasive candidiasis greater than 2.5% or fluconazole resistance less than 24.0%. For higher resistance levels, empirical caspofungin therapy is preferred. For low prevalences of invasive candidiasis, culture-based fluconazole is reasonable. For prevalences exceeding 60%, empirical caspofungin therapy is reasonable. For caspofungin to be reasonable at a prevalence of 10%, its cost must be reduced by 58%.. Less severe illness and limited use of broad-spectrum antimicrobial agents, typical of smaller hospitals, could result in a lower risk for invasive candidiasis.. In patients in the ICU with suspected infection who have not responded to antibiotic treatment, empirical fluconazole should reduce mortality at an acceptable cost. The use of empirical strategies in low-risk patients is not justified.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Caspofungin; Cost-Benefit Analysis; Cross Infection; Decision Support Techniques; Echinocandins; Fluconazole; Humans; Intensive Care Units; Lipopeptides; Microbiological Techniques; Peptides, Cyclic; Prevalence; Risk Factors; Sensitivity and Specificity; Treatment Outcome

The spectrum of candidiasis has changed with the emergence of non-albicans Candida spp. and acquired antifungal resistance, especially in immunocompromised hosts. This changing scenario has necessitated routine antifungal susceptibility testing. In the present work, 102 Candida spp. isolates gathered during 2003 - 2004 were characterized by standard procedures, and antifungal susceptibility testing to amphotericin B, fluconazole and itraconazole was performed by broth macrodilution (BMD)-minimum inhibitory concentration (MIC) and disk diffusion (DD) methods. Among all isolates, 77.4% were from an ICU and 10.8% were obtained from a nursery. The majority of the isolates were C. tropicalis (48%), followed by C. parapsilosis (27.4%) and C. albicans (22.5%). Overall 6.9, 4.9 and 3.9% of all isolates were resistant to amphotericin B, fluconazole and itraconazole, respectively. Out of the 5 (4.9%) isolates resistant to fluconazole, 4 (3.9%) were from patients with AIDS on fluconazole prophylaxis. A discrepancy was observed between the results of susceptibility testing by DD and those by BMD-MIC: 15 (14.7%) isolates were reported to be resistant by DD despite having low MICs. Based on these results, it was concluded that initial antifungal screening of clinical isolates by the DD method followed by confirmation of resistant strains by the broth dilution method is desirable to optimize patient management.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Communicable Diseases, Emerging; Drug Resistance, Fungal; Female; Fluconazole; Hospitals; Humans; Itraconazole; Male

In an experiment conducted using male CBA mice, cellular events during granulomatous Candida-induced inflammation were studied both in untreated animals and in animals treated with a new lysosomotropic composition, consisting of amphotericin B in intracellularly prolonged dextran immunomodulating matrix. To induce systemic Candida granulomatous inflammation, mice were given a single 0.2 ml intraperitoneal injection of Candida albicans culture (2.5 x 10(9) microbial bodies) dissolved in 0.9% isotonic saline. The findings obtained indicate greater therapeutic effect of amphotericin B and dextran dialdehyde composition as compared with a free (unconjugated) form of amphotericin B, that was manifested by the disappearance of granulomas and the capacity to prevent the development of spontaneous destructive processes in granulomas. Independent antimycotic effect of dextran dialdehyde was also demonstrated.

Topics: Amphotericin B; Animals; Candida albicans; Candidiasis; Dextrans; Granuloma; Lymph Nodes; Lymphatic Diseases; Male; Mice; Mice, Inbred CBA

The aim of this study was to evaluate species distribution and antifungal susceptibility of Candida blood isolates in Japan.. In a 1 year surveillance programme, 535 Candida blood isolates were collected. Identification of species was followed by examination with the broth microdilution method, as described in NCCLS M27-A2, of antifungal susceptibility to six agents, including voriconazole and micafungin, with readings after 24 and 48 h of incubation.. The overall species distribution was: 41% Candida albicans, 23% Candida parapsilosis, 18% Candida glabrata, 12% Candida tropicalis and 2% Candida krusei. The concentrations of fluconazole necessary to inhibit 90% of the isolates (MIC(90)) at 24/48 h were 0.25/1 mg/L for C. albicans, 0.5/2 mg/L for C. parapsilosis, 4/32 mg/L for C. glabrata and 4/>128 mg/L for C. tropicalis. Percentages of fluconazole resistance were 1.8% for C. albicans, 0.8% for C. parapsilosis, 5.2% for C. glabrata and 3.2% for C. tropicalis, taking the tendency of trailing growth of C. tropicalis into account. MIC(90) of voriconazole was 0.5 mg/L, although 35% of isolates less susceptible (>/=16 mg/L) to fluconazole showed resistance (>/=2 mg/L). Micafungin was very active against all species (MIC(90), 0.03 mg/L) except for C. parapsilosis (MIC(90), 2 mg/L).. These data suggest that, in Japan, the species distribution of Candida bloodstream infections and the fluconazole resistance rate are similar to those reported previously in North America and Europe. Voriconazole and micafungin appear to have strong in vitro activity against Candida blood isolates, although continuing surveillance and further clinical research are needed.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Echinocandins; Flucytosine; Humans; Itraconazole; Japan; Lipopeptides; Lipoproteins; Micafungin; Microbial Sensitivity Tests; Peptides, Cyclic; Pyrimidines; Triazoles; Voriconazole

To report the unusual occurrence of a recurrent scleral abscess after uncomplicated cataract extraction.. Case report of a 77-year-old healthy woman.. Multiple cultures and antibiotic treatments failed to resolve presenting symptoms. Gram stain, Gomori methenamine silver (GMS) stain, and all cultures were negative. After drainage of the abscess, the patient's symptoms cleared briefly, then returned 6 months later showing a positive GMS stain consistent with Candida. The patient was treated with amphotericin, natamycin, and fluconazole at this time, and a return in visual acuity occurred along with a resolution of symptoms. No re-occurrence has been noted with 2.5 years of follow-up.. Cataract extraction, although generally a safe procedure, can still result in unusual complications such as scleral abscesses. Excellent outcomes are possible once the infections are identified and treated.

Topics: Abscess; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Cataract Extraction; Drug Therapy, Combination; Female; Fluconazole; Humans; Natamycin; Recurrence; Scleral Diseases

To determine the susceptibilities of Candida species isolated from Taiwan to amphotericin B and fluconazole.. Prospective surveillance study.. Each hospital was asked to submit up to 10 C. albicans and 40 non-albicans Candida species during the collection period, from April 15 to June 15, 1999. One isolate was accepted from each episode of infection. The broth microdilution method was used to determine susceptibilities to amphotericin B and fluconazole.. Only 3 of 632 isolates, one each of C. famata, C. krusei, and C. tropicalis, were resistant to amphotericin B. A total of 53 (8.4%) of 632 clinical yeast isolates, consisting of 4% C. albicans, 8% C. glabrata, 15% C. tropicalis, and 70% C. krusei, were resistant to fluconazole. In contrast, no C. parapsilosis isolate was resistant to fluconazole. Isolates from tertiary-care medical centers had higher rates of resistance to fluconazole than did those from regional and local hospitals (11.4% vs 6.6%). Isolates from different sources showed different levels of susceptibility to fluconazole. All of the isolates with the exception of C. tropicalis and C. krusei isolated from blood were susceptible to fluconazole. A pattern of co-resistance to both amphotericin B and fluconazole was observed.. Non-albicans Candida species had higher rates of resistance to fluconazole than did C. albicans (44 of 395 [11.2%] vs 9 of 237 [3.8%]; P = .002). The increasing rate of fluconazole resistance in C. tropicalis (15%) is important because C. tropicalis is one of the most commonly isolated non-albicans Candida species.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida tropicalis; Candidiasis; Cross Infection; Drug Resistance, Microbial; Fluconazole; Humans; Microbial Sensitivity Tests; Prospective Studies; Taiwan

Susceptibilities to amphotericin B and fluconazole of 383 Candida species isolated from blood were determined. Candida albicans was the most common species (55.6%), followed by Candida parapsilosis (17.5%), Candida tropicalis (16.5%), Candida glabrata (5.2%), Candida guilliermondii (2.3%), and others (2.9%). All but three isolates, Candida ciferrii, C. tropicalis, and C. glabrata, one each, were susceptible to amphotericin B. A total of 367 (95.8%) and 15 (4.2%) isolates were susceptible and susceptible-dose dependent to fluconazole, respectively. Only one isolate, a C. glabrata, was resistant to fluconazole. Few patients (13%) having prior fluconazole treatments may explain the low rate of resistance to fluconazole in this study.

Topics: Amphotericin B; Candida; Candidiasis; Drug Resistance, Fungal; Fluconazole; Fungemia; Humans; Microbial Sensitivity Tests; Retrospective Studies; Sampling Studies; Sensitivity and Specificity

The aim of the present study was to expand the MIC database for Candida lusitaniae in order to further determine its antifungal susceptibility pattern.. The activities of amphotericin B, fluconazole, itraconazole, voriconazole and flucytosine were determined in vitro against 80 clinical isolates of C. lusitaniae. A set of 59 clinical isolates of Candida albicans and of 51 isolates of Candida glabrata was included to compare the susceptibilities to amphotericin B. The MICs were determined by Etest with RPMI 1640 agar, and with both this medium and antibiotic medium 3 (AM3) agar for testing of amphotericin B.. All isolates were highly susceptible to fluconazole. The susceptibility to itraconazole was good; only 4% of isolates had dose-dependent susceptibility (MICs 0.25-0.5 mg/L). Voriconazole was very active in vitro (100% of isolates were inhibited at < or =0.094 mg/L). Flucytosine MICs ranged widely (0.004->32 mg/L). The set included 19% of flucytosine-resistant isolates. For amphotericin B, 100% of isolates were inhibited at < or =0.75 mg/L (MIC(50) 0.047 mg/L; MIC(90) 0.19 mg/L) and at < or =4 mg/L (MIC(50) 0.25 mg/L; MIC(90) 0.75 mg/L) on RPMI and on AM3, respectively. A single isolate was categorized as resistant to amphotericin B (MIC 0.75 and 4 mg/L on RPMI and on AM3, respectively). Amphotericin B thus appeared very active in vitro against C. lusitaniae. Whatever the test medium, the level of susceptibility of C. lusitaniae to amphotericin B did not differ much from those of C. albicans and C. glabrata.. C. lusitaniae appears to be susceptible to amphotericin B, azole antifungal agents, and, to a lesser extent, flucytosine.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Humans; Microbial Sensitivity Tests

Advances in medical therapy have greatly improved the survival of children suffering from cancer. Although progress has been made in the eradication of malignant disease there is growing concern for the development of fungal infections in patients treated with chemotherapy.. We reviewed all episodes of pediatric candidemia that occurred between January 1988 and December 2000. We analyzed the general characteristics of this population, risk factors, microbiology features, treatment, complications, and outcome.. Seventeen cases of candidemia were observed during the 12 years of the study at an estimated incidence of 0.4%. Neutropenia occurred at the onset of infection in 13/17 (76.5%) children. A central venous device was present in all cases. Seventy-seven percent of the infections were caused by Candida albicans and in 85% of patients, yeasts had colonized the gastrointestinal tract. In 9/17 patients visceral dissemination was documented. Overall, in 77% of the episodes the outcome was favorable.. Candidemia is a rare but severe complication in pediatric oncology. Even if the prognosis is better in children than in adults, Candida septicemia remains of great concern since a high percentage of these infections result in visceral dissemination and mortality is still elevated.

Topics: Adolescent; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Candidiasis; Child; Child, Preschool; Female; Humans; Incidence; Infant; Male; Neoplasms; Retrospective Studies; Risk Factors; Treatment Outcome

We determined the in vitro susceptibilities of 643 strains of Candida spp., representing 13 species rarely isolated from blood, to ravuconazole as well as three licensed systemic antifungal agents (amphotericin B, fluconazole, and flucytosine). The organisms included 234 isolates of C. krusei, 102 isolates of C. guilliermondii, 103 isolates of C. lusitaniae, 18 isolates of C. famata, 29 isolates of C. kefyr, 20 isolates of C. pelliculosa, 13 isolates of C. rugosa, 101 isolates of C. dubliniensis, 4 isolates of C. inconspicua, 11 isolates of C. lipolytica, 1 isolate of C. sake, and 2 isolates of C. lambica and 5 isolates of C. zeylanoides. MIC determinations were made by the National Committee for Clinical Laboratory Standards reference broth microdilution method and Etest (amphotericin B). Ravuconazole demonstrated excellent activity (98% susceptible at MIC < or = 1 microg/mL) against all species with the exception of C. inconspicua (75% [3 of 4]). By comparison, decreased susceptibility to fluconazole and/or amphotericin B was observed among isolates of C. krusei, C. guilliermondii, C. famata, C. rugosa, C. inconspicua, and C. lambica. These findings illustrate the fact that many of the less common species of Candida exhibit decreased susceptibility to one or more of the established systemically active antifungal agents. Ravuconazole is clearly an "extended-spectrum" triazole with potent in vitro activity against these rare and potentially "emerging" opportunistic pathogens.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Fluconazole; Flucytosine; Fungemia; Humans; Microbial Sensitivity Tests; Thiazoles; Triazoles

We describe the case of a patient with chronic monocytic leukemia who underwent total hip arthroplasty (THA) for hip arthrosis. The patient has a history of Candida albicans arthritis of the same joint 5 months before THA surgery. Seven months after the prosthetic joint surgery, the patient developed a C albicans prosthetic infection that was successfully treated with amphotericin B and prosthesis removal. At surgery, the patient was believed cured of the candidal infection. Risk of infection after prosthetic joint surgery in patients with previous fungal joint infections has not been fully investigated. A lengthy infection-free follow-up period is probably necessary but may not be sufficient to prevent the occurrence of postoperative infections in these patients.

Topics: Amphotericin B; Antifungal Agents; Arthritis, Infectious; Arthroplasty, Replacement, Hip; Candidiasis; Device Removal; Hip Joint; Hip Prosthesis; Humans; Male; Middle Aged; Prosthesis-Related Infections; Recurrence

To describe the response of a child with persistent fungemia to caspofungin, a member of the echinocandin class of antifungals.. Descriptive case report.. Pediatric intensive care unit at a university teaching hospital.. A 3-yr-old female with persistent candidemia.. After >5 wks of persistent candidemia, caspofungin was added to an antifungal regimen that included amphotericin B and flucytosine.. The addition of caspofungin resulted in rapid clearance of the candidemia. The child recovered without evidence of further fungal infection or overt toxicity.. Caspofungin was administered safely in this pediatric patient and possibly contributed to her clinical improvement. Caspofungin may be considered in children with severe persistent fungal infections that are not responsive to standard therapy. More study in pediatric patients is necessary before recommending its general use.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Child, Preschool; Drug Therapy, Combination; Echinocandins; Endocarditis; Female; Flucytosine; Fungemia; Humans; Lipopeptides; Peptides; Peptides, Cyclic

One month after penetrating keratoplasty, a male patient suffered recurrent abscess and endophthalmitis caused by mixed bacteria (Staphylococcus aureus and Candida Albicans).. Two samples of vitreous and aqueous were taken, and a combination of systemic Vancomycin and Amphotericin B were injected intravitreally. The patient was asymptomatic for a month, but the abscess reactivated and was treated with Vancomycin and Ciprofloxacin administered intravenously. Fifteen days after withdrawing the treatment endophthalmitis returned and was treated with vitrectomy and additional systemic/intravitreal antibiotics and antifungal therapy. The final visual acuity was 20/40.. The delayed vitrectomy proved to be necessary to remove established germs and to eliminate recurrent infections.

Topics: Abscess; Adult; Amphotericin B; Aqueous Humor; Candida albicans; Candidiasis; Ciprofloxacin; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Bacterial; Eye Infections, Fungal; Humans; Keratoplasty, Penetrating; Male; Postoperative Complications; Recurrence; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin; Vitreous Body

(1) Amphotericin B is the antifungal drug of choice for the treatment of invasive aspergillosis, severe candidiasis and Fusarium infection. Voriconazole is an antifungal azole sold in France for oral and intravenous treatment of these infections. (2) In 391 patients with established or probable invasive aspergillosis, combined analysis of two trials comparing voriconazole (intravenously then orally) with conventional amphotericin (intravenously) showed that the 12-week survival rate was significantly higher with voriconazole (70.8% versus 57.9%). Unfortunately, these results are undermined by methodological flaws such as the lack of blinding, the very different intravenous treatment periods in the two groups, and subsequent oral treatment with different antifungal drugs. Voriconazole has not been compared with liposomal amphotericin B. (3) In the treatment of severe candidiasis, and severe Scedosporium and Fusarium infections, we only have the (favourable) results of non comparative trials in small numbers of patients refractory to other antifungal drugs. (4) The main adverse effects were visual disturbances, elevated hepatic enzyme levels, acute renal failure, and sometimes serious cutaneous reactions. It lengthens the QT interval and can cause torsades de pointes. It inhibits the cytochrome P450 isoenzymes CY3A4, CYP2C9 and CYP2C19, hence a high risk of potentially serious drug interactions. (5) Voriconazole can be given by mouth or by IV infusion, whereas liposomal amphotericin B must be given intravenously. (6) In practice, another more rigorous trial is needed to confirm the favourable results obtained with voriconazole in invasive aspergillosis. Voriconazole is the first-line treatment for severe Scedosporium infections, despite limited experience. It is a last resort for severe candidiasis and severe Fusarium infection.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Drug Interactions; Fusarium; Humans; Immunocompromised Host; Mycetoma; Mycoses; Pyrimidines; Scedosporium; Treatment Outcome; Triazoles

Facial cellulitis caused by odontogenic bacterial infection is frequently encountered; however, facial cellulitis caused by Candida albicans infection is rarely found. A patient with oral submucous fibrosis (OSF) and unknown diabetes mellitus (DM) was treated in our out-patient dental clinic by biweekly submucosal injection of 40 mg triamcinolone acetonide into bilateral buccal mucosae plus forced mouth opening performed by the two hands of the clinician. The interincisal distance of the patient improved from 28 to 48 mm after four times of steroid injection. The symptoms and signs of OSF also improved markedly. Unfortunately, facial candidal cellulitis occurred 2 months after the last time of steroid injection treatment. The infection was cured by incision and drainage, intravenous administration of amphotericin B (100 mg once a day for a week), and an appropriate medical control of DM. No recurrence of facial cellulitis was found during the follow-up period of 18 months. To prevent the occurrence of facial cellulitis after a high-dose steroid therapy, some prophylactic procedures should be taken before the initiation of the steroid treatment.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cellulitis; Diabetes Complications; Drainage; Face; Follow-Up Studies; Glucocorticoids; Humans; Male; Middle Aged; Oral Submucous Fibrosis; Triamcinolone Acetonide

Catheter-related infections due to Candida albicans biofilms are a leading cause of fungal nosocomial bloodstream infection. In this paper, we describe the development of a model of catheter-associated infection with C. albicans biofilms and show that antifungal lock therapy with liposomal amphotericin B is an effective treatment strategy for these infections. Silicone catheters surgically placed in New Zealand White rabbits were infected with C. albicans, and the rabbits were randomized into three groups: (i) untreated controls, (ii) liposomal amphotericin B lock, and (iii) fluconazole lock. Upon completion of therapy, blood cultures were obtained and the catheters were removed for quantitative culture and scanning electron microscopic analyses. Quantitative cultures revealed that catheters treated with liposomal amphotericin B yielded 0 CFU, which was significant compared to the untreated controls (P < 0.001) and the fluconazole-treated group (P = 0.0079). Although fluconazole treatment tended to have lower CFU compared to untreated controls, there was no difference in mean colony counts between these two groups (1.128 +/- 0.764 and 1.841 +/- 1.141 log(10) CFU/catheter segment, respectively; P = 0.297). Scanning electron microscopy revealed abundant biofilm in the control and fluconazole groups, while the liposomal amphotericin B group was virtually cleared. These findings suggest a possible treatment strategy for the successful salvage of catheters infected with C. albicans biofilms and describe an animal model that may play an important role in the further study of C. albicans biofilm pathogenesis and evaluation of potential antibiofilm agents.

Topics: Amphotericin B; Animals; Antifungal Agents; Biofilms; Candidiasis; Catheterization, Central Venous; Colony Count, Microbial; Drug Carriers; Drug Resistance, Fungal; Liposomes; Microscopy, Electron, Scanning; Rabbits

(1) The reference treatment for invasive candidiasis in patients without neutropenia is standard amphotericin B. If this treatment fails or is too nephrotoxic, second-line alternatives are liposomal amphotericin B and fluconazole. Voriconazole is a third-line option. (2) Caspofungin, an antifungal drug belonging to the echinocandin class, is now approved for use in this indication in France. (3) The clinical evaluation dossier contains no data from comparative trials with fluconazole or voriconazole. It only gives the results of a double-blind trial in 239 patients, designed to show simply that caspofungin was not inferior to standard amphotericin B. Most of the patients did not have neutropenia. About one-third of the patients died. There was no difference in mortality between the two groups. No data are available from trials versus other forms of amphotericin B. (4) In this trial, caspofungin had fewer adverse effects (especially nephrotoxicity) than standard amphotericin B. However, in other trials in other indications, caspofungin had more adverse effects than fluconazole. (5) In France, caspofungin costs nearly 100 times more than standard amphotericin B. (6) In practice, caspofungin has no proven advantages over existing options for the treatment of invasive candidiasis in patients without neutropenia.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Fluconazole; France; Humans; Peptides; Pyrimidines; Triazoles

Greater use of invasive procedures and aggressive antimicrobial therapy predispose extremely low birth weight (ELBW) infants to systemic fungal sepsis. Despite its adverse effects (including renal and electrolyte disturbances), amphotericin B (amphoB) remains the preferred drug for fungal therapy. Multiple studies have indicated that sodium loading may prevent renal toxicity among animals and human adults. The effects of fluid and electrolyte management on amphoB-induced nephrotoxicity among ELBW infants have not been evaluated extensively. The purpose of this study was to examine the effects of fluid and electrolyte management on amphoB-induced nephrotoxicity among ELBW infants.. The medical records were reviewed for all ELBW infants (birth weights of < or =1250 g) who developed systemic fungal sepsis, requiring amphoB therapy, between January 1992 and December 2000. Demographic, clinical, and laboratory data were collected from the medical records for each patient.. Fungal sepsis requiring amphoB treatment developed for 4.4% of ELBW infants (25 of 573 infants), with a gestational age of 25 +/- 1 weeks and a birth weight of 738 +/- 37 g, at a postnatal age of 16 +/- 2 days. Renal compromise, as manifested by low urine output and high creatinine levels, occurred for 44% of those infants (11 of 25 infants). There was no difference between the infants who developed renal compromise (renal compromise group [RCG], n = 11) and those who did not (no-renal-compromise group [NCG], n = 14) with respect to birth weight, gestational age, and risk factors predisposing the infants to fungal sepsis. The RCG demonstrated a decrease in urine output by 3.4 +/- 2 days and an increase in serum creatinine levels by 3.9 +/- 2 days after the initiation of amphoB therapy. Infants in the RCG had a significantly higher incidence of hyponatremia, compared with infants in the NCG (7 of 11 infants vs 0 of 14 infants), with no significant difference in the incidences of hypokalemia (2 of 11 infants vs 0 of 14 infants). Infants in the RCG, compared with infants in the NCG, had significantly lower mean daily sodium intakes in the 4 days before the initiation of amphoB therapy (2.6-2.9 mEq/kg per day vs 4.2-4.7 mEq/kg per day) and in the first 4 days of amphoB treatment (2.7-3.1 mEq/kg per day vs 4.5-5.6 mEq/kg per day). Mean daily sodium intakes were not statistically significantly different between the 2 groups between day 5 and day 10 of amphoB therapy. Infants in the RCG tended to have lower mean daily potassium intakes in the 4 days before the initiation of amphoB therapy and during the first 4 days of amphoB therapy. Subsequently, the mean daily potassium intakes remained not statistically significantly different between the groups. Mean daily fluid intakes were not different between the groups.. Conventional amphoB combined with adequate hydration and higher sodium intakes of >4 mEq/kg per day may provide effective protection against amphoB-induced nephrotoxicity among ELBW infants. Our data confirm the published results of animal and human adult studies and suggest that higher sodium intakes may prevent renal compromise during amphoB therapy among ELBW infants.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Creatinine; Female; Fluid Therapy; Fungemia; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Kidney Diseases; Male; Potassium; Retrospective Studies; Risk Factors; Sodium; Water-Electrolyte Balance

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Humans; Infant, Newborn; Liposomes; Research Design

The aim was to evaluate the in vitro activity of voriconazole compared with those of amphotericin B, itraconazole and fluconazole against 132 bloodstream isolates of Candida non-albicans and Saccharomyces cerevisiae species. The minimal inhibitory concentrations (MICs) were determined by an adapted National Committee for Clinical Laboratory Standards (NCCLS) M27-A method using RPMI 1640 as test medium supplemented with 2% glucose. MIC end-points were determined with a spectrophotometer after incubation for 48 h at 35 degrees C. Optical density data were used for the calculation of the MIC end-points. For amphotericin B, the end-point was defined as the minimal antifungal concentration that exerts 90% inhibition compared with the control well growth. For the azoles, the end-points were determined at 50% inhibition of growth. Amphotericin B is highly active with 97% of isolates inhibited by < or =1 microg ml(-1). Decreased susceptibility or resistance to fluconazole was the rule among C. krusei, which is intrinsically resistant to fluconazole. For C. glabrata isolates, resistance to fluconazole and itraconazole was measured in 13% and 17% of the isolates respectively. Voriconazole was quite active in vitro against all the isolates with a MIC90% of < or =1 microg ml(-1) and we conclude that it may be useful in the treatment of non-albicans bloodstream infections.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Fluconazole; Humans; Itraconazole; Microbial Sensitivity Tests; Pyrimidines; Saccharomyces cerevisiae; Triazoles; Voriconazole

The aim of this study was to identify changes in the gene expression profile of Candida albicans associated with the acquisition of experimentally induced resistance to amphotericin B and fluconazole.. C. albicans SC5314 was passed in increasing concentrations of amphotericin B to generate isolate SC5314-AR. Susceptibility testing by Etest revealed SC5314-AR to be highly resistant to both amphotericin B and fluconazole. The gene expression profile of SC5314-AR was compared with that of SC5314 using DNA microarray analysis. Sterol composition was determined for both strains.. Upon examination of MICs of antifungal compounds, it was found that SC5314-AR was resistant to both amphotericin B and fluconazole. By microarray analysis a total of 134 genes were found to be differentially expressed, that is up-regulated or down-regulated by at least 50%, in SC5314-AR. In addition to the cell stress genes DDR48 and RTA2, the ergosterol biosynthesis genes ERG5, ERG6 and ERG25 were up-regulated. Several histone genes, protein synthesis genes and energy generation genes were down-regulated. Sterol analysis revealed the prevalence of sterol intermediates eburicol and lanosterol in SC5314-AR, whereas ergosterol was the predominant sterol in SC5314.. Along with changes in expression of these ergosterol biosynthesis genes was the accumulation of sterol intermediates in the resistant strain, which would account for the decreased affinity of amphotericin B for membrane sterols and a decreased requirement for lanosterol demethylase activity in membrane sterol production. Furthermore, other genes are implicated as having a potential role in the polyene and azole antifungal resistant phenotype.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Cytochrome P-450 Enzyme System; DNA Primers; DNA, Complementary; Drug Resistance, Fungal; Ergosterol; Fluconazole; Gene Expression Profiling; Genes, Fungal; Genome, Fungal; Humans; Microbial Sensitivity Tests; Oligonucleotide Array Sequence Analysis; Oxidoreductases; Phenotype; Protein Folding; Reverse Transcriptase Polymerase Chain Reaction; RNA, Fungal; Saccharomyces cerevisiae; Sterol 14-Demethylase; Sterols

In a previous study tolerance to amphotericin B (AMB) was found among Candida parapsilosis and C. dubliniensis strains by seeding the whole volumes of wells used for MIC determinations, and minimum fungicidal concentrations (MFC) for non-C. albicans Candida strains were demonstrated to be above the levels safely achievable in serum. As an extension of that study, we performed time-kill assays with 26 blood culture isolates (6 C. albicans, 5 C. parapsilosis, 5 C. krusei, 4 C. glabrata, 3 C. lusitaniae, and 3 C. tropicalis isolates), 3 oropharyngeal C. dubliniensis isolates, 3 AMB-susceptible isolates (ATCC 90028, ATCC 22019, ATCC 6254), and 6 AMB-resistant isolates (ATCC 200955, ATCC 200956, ATCC 200950, ATCC 200951, ATCC 200952, ATCC 200953) using RPMI 1640 medium and 0.12 to 32 microg of AMB per ml and determined the numbers of CFU per milliliter at 0, 2, 4, 8, 12, 24, and 48 h. MFCs and time-kill patterns were species specific (MFCs, < or =1 microg/ml for all C. dubliniensis and C. albicans isolates except AMB-resistant strain ATCC 200955; MFCs, 2 to >16 microg/ml for the other isolates). The times required to reach the fungicidal endpoint (99.9% killing) at four times the MIC were 2 h for C. albicans and C. dubliniensis, 16 h for C. glabrata, 24 h for C. parapsilosis and C. lusitaniae, and > or =40 h for C. tropicalis and C. krusei. The killing rate increased as the AMB concentration was increased up to 2 microg/ml. The highest killing rates were achieved for C. albicans, C. dubliniensis, and C. lusitaniae, while viable C. tropicalis, C. krusei, and C. parapsilosis cells were present after 48 h (MICs, < or =2 microg/ml) when AMB was used at 2 microg/ml. Time-kill curves and MFCs can detect viable cells after 48 h when AMB is used at > or =2 microg/ml. The failure of AMB treatment could be due to its poor killing activity against some species at the concentrations reached in patients' serum.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Humans; Microbial Sensitivity Tests; Models, Statistical; Time Factors

Amphotericin B failure is frequently seen in patients with candidaemia caused by Candida rugosa. We evaluated amphotericin B, fluconazole, posaconazole and voriconazole as alternative treatments against infection in mice with two isolates of C. rugosa.. Neutropenic mice were inoculated intravenously with C. rugosa. Amphotericin B, fluconazole, posaconazole and voriconazole were administered for 7 days after infection. Efficacy of the antifungal treatment was assessed by survival and tissue burden of C. rugosa.. All of the four drugs significantly prolonged survival over controls. With both isolates, kidney counts were reduced significantly below controls for amphotericin B, fluconazole and posaconazole. However, voriconazole was less effective than the other antifungals.. Despite poor clinical response to amphotericin B, in vivo data indicate that amphotericin B increases organ clearance and survival over untreated controls. However, although voriconazole improved survival over controls, increased tissue clearance was not seen. This discrepancy may be caused by rapid clearance of voriconazole in mice. These studies suggest fluconazole, posaconazole or voriconazole may be useful alternatives to amphotericin B in therapy of C. rugosa infection.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Colony Count, Microbial; Fluconazole; Kidney; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Neutropenia; Organ Size; Pyrimidines; Spleen; Survival Analysis; Triazoles; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Fungemia; Humans; Pyrimidines; Randomized Controlled Trials as Topic; Treatment Outcome; Triazoles; Voriconazole

Invasive fungal infections are more commonly found in patients who develop neutropenia after chemotherapy. A 4-year-old girl with diagnosis of acute lymphoid leukemia developed febrile neutropenia after chemotherapy. Broad spectrum antibiotics and antimycotic therapy were initiated. Candida albicans was isolated and Entamoeba histolytica was observed in stool examination. Chronic disseminated candidiasis had developed and was treated with amphotericin B, initially, and fluconazol. Computed tomography images were obtained that demonstrated a classic 'bull's eye' pattern; a concurrent histological study confirmed the diagnosis. Candida spp. is the major cause of opportunistic mycosis in immunosuppresed patients receiving chemotherapy for haematologic malignancies. An initial infection results in disseminated candidiasis, which persists and becomes chronic. In the 4-year-old patient, the identified risk factors consisted of a previous therapy with broad spectrum antibiotics, the gastrointestinal tract colonization with Candida albicans and prolonged neutropenia. Imaging diagnoses are made by ultrasonography, computed tomography and magnetic resonance. With ultrasound and tomography, 4 distinct patterns have been described. Pattern 1 ('wheels within wheels') and 2 ('bull's eye') are important, since they are characteristic of chronic disseminated candidiasis. The third pattern (hypoechoic image) is the most common finding with both techniques. In the current patient, patterns 2 and 3 were seen and the diagnosis was confirmed by histological study.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Child, Preschool; Drug Therapy, Combination; Entamoeba histolytica; Feces; Female; Fluconazole; Humans; Liver Abscess; Tomography, X-Ray Computed

Prosthetic valve endocarditis (PVE) caused by Candida species is associated with high morbidity and mortality. A combination of surgical resection and antifungal drug therapy is the golden standard for treatment, yet surgical intervention is not possible in all cases of Candida PVE. We report a case of PVE due to Candida albicans cured by medical treatment alone. This case suggests that, in some instances, Candida PVE can be managed medically with antifungal therapy. Such a conservative approach should be applied with caution and necessitates very close follow-up on a long-term basis.

Topics: Amphotericin B; Antifungal Agents; Aortic Valve; Candida albicans; Candidiasis; Endocarditis, Bacterial; Female; Fluconazole; Heart Valve Prosthesis; Humans; Middle Aged; Treatment Outcome

To present a case of Candida parapsilosis following laser in situ keratomileusis (LASIK).. Retrospective chart review.. A case report of a 51-year-old woman who underwent bilateral LASIK is presented. Two weeks after the procedure, the patient presented with epithelial ingrowth OD. The ingrowth was treated with flap lifting and scraping, followed by postoperative antibiotics. Four weeks later, the patient presented with numerous interface infiltrates. Smears were positive for yeast forms and cultures grew Candida parapsilosis. Administration of topical and systemic antifungal therapy resulted in clearing of the infection with partial visual recovery.. To our knowledge, this represents the first reported case of a post-LASIK Candida parapsilosis keratitis. A high degree of suspicion coupled with rapid and appropriate treatment can result in visual recovery.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Debridement; Drug Therapy, Combination; Epithelium, Corneal; Eye Infections, Fungal; Female; Fluconazole; Humans; Keratitis; Keratomileusis, Laser In Situ; Middle Aged; Ofloxacin; Postoperative Complications; Retrospective Studies; Surgical Flaps

The in vivo efficacy of a new amphotericin B (AmB) oil-in-water lecithin-based microemulsion delivery system (M-AmB) compared to deoxycholate-AmB (D-AmB) was studied in an immunocompetent and neutropenic murine model of systemic candidiasis. D-AmB was administered at the maximum tolerated dose of 1 mg/kg whereas M-AmB was given at the doses of 1, 2 and 3 mg/kg; doses were well tolerated due to their reduced toxicity. Both formulations were administered 24, 48 and 72 h after infection in immunocompetent mice, and 2, 6 and 24 h after infection in neutropenic mice. Kaplan-Meier survival curves showed that the M-AmB treated group had a better survival time than infected mice without treatment used as a control group (P = 4.66 x 10(-6)), and the Mann-Whitney W statistical test indicated that it reduced the percentage of mortality and fungal load in the most representative organs. This new formulation is a designed competitor which has proved to present better results than D-AmB in an established infection not only in immunocompetent but in neutropenic mice as well.

Topics: Amphotericin B; Animals; Candidiasis; Chemistry, Pharmaceutical; Deoxycholic Acid; Emulsions; Freeze Drying; Immunocompetence; Male; Mice; Neutropenia; Phosphatidylcholines

We determined the antifungal susceptibility of 50 Candida isolates from invasive mycoses in intensive care unit patients in Chile. Candida albicans (27 isolates) and C. parapsilosis (12 isolates) were the most common etiologic species. Candida glabrata (five isolates) was isolated only from children. Our data are consistent with those of recent Brazilian and Argentinean studies but differ from those of some US, Canadian and Norwegian studies, in which the relatively azole-resistant C. glabrata was the predominant non-C. albicans species seen. All isolates in this study were susceptible to amphotericin B. Itraconazole and fluconazole resistance were observed in 6 and 4% of the isolates, respectively.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candidiasis; Chile; Critical Care; Drug Resistance, Fungal; Fluconazole; Humans; Inpatients; Intensive Care Units; Itraconazole; Ketoconazole; Microbial Sensitivity Tests

This study presents the efficiency of the experimental antifungal agents 6-amino-2-n-pentylthiobenzothiazole (APB) and the echinocandin micafungin, and amphotericin B against fluconazole-resistant Candida albicans and Candida dubliniensis (MIC95 for fluconazole > 64 mg/l). The benzothiazole APB was less active against C. albicans and C. dubliniensis (MIC80 = 8 - 32 mg/l, MIC95 = 16 - 64 mg/l) than amphotericin B, which was efficient in a concentration range from 0.125 to 2 mg/l. However, the efficiency of micafungin was very high with MIC80, and MIC100 < or = 0.031 mg/l.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candidiasis; Drug Resistance, Fungal; Echinocandins; Fluconazole; Humans; Lipopeptides; Lipoproteins; Micafungin; Microbial Sensitivity Tests; Peptides, Cyclic; Thiazoles

Topics: Amphotericin B; Animals; Antifungal Agents; Candida glabrata; Candidiasis; Catheters, Indwelling; Colony Count, Microbial; Diagnostic Errors; Humans; Leukemia, Myeloid; Platelet Count; Thrombocytopenia

Amphotericin B may be employed as a potentially toxic deoxycholate complex or incorporated in liposomes and other particles which have an altered tissue distribution. A combination of both preparations could help to overcome the drawbacks of the individual preparations. We have employed a mouse model of systemic infection with Candida albicans to investigate whether this assumption was essentially true. We found that the combination of low dosages of both preparations (0.5 mg/kg of body weight/day of conventional and 0.5 mg kg of body weight/day liposomal amphotericin B) was more efficient than a similar dosage of conventional amphotericin B (1 mg/kg of body weight/day) in the liver and similar or higher dosages of liposomal amphotericin B (1 or 5 mg/kg of body weight/day) in the kidneys.

Topics: Amphotericin B; Animals; Candida albicans; Candidiasis; Chemistry, Pharmaceutical; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Carriers; Female; Fungemia; Liposomes; Mice; Mice, Inbred BALB C; Probability; Sensitivity and Specificity; Treatment Outcome

Musculoskeletal candidiasis occurs in some patients with candidemia resulting from organ infection, IV drug use, or indwelling central venous catheters. Diagnosis is often difficult because of vague symptomatology and a frequent afebrile course.. Three patients with Candida vertebral osteomyelitis are presented. All followed the use of indwelling central venous access catheters and antimicrobial therapy between 6 months and 3 years earlier. In 2, fungemia with the same Candida spp. preceded the spondylodiskitis. These 3 patients bring to nearly 75 the number of reported individuals with what was once quite rare. Although IV amphotericin B doxycholate and fluconazole have usually been effective therapy over prolonged periods of time, we used liposomal amphotericin B to treat 2 of our 3 patients. Both received 5 mg/kg daily for 18-42 days that resulted in total disappearance of signs and symptoms.. This relatively brief duration of therapy reduces treatment time and is cost-effective.

Topics: Aged; Amphotericin B; Antifungal Agents; Candidiasis; Discitis; Drug Administration Schedule; Drug Combinations; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteomyelitis; Phosphatidylcholines; Phosphatidylglycerols; Thoracic Vertebrae

Although Candida species are present as normal microflora of the human host, alterations in host defenses can lead to development of disease. Candida infections, ranging from urinary tract infections to bloodstream infections, are common in patients in the intensive care unit. Infections with non-albicans Candida sp are becoming more frequent, and resistance among these isolates is concerning. Candida kefyr is an uncommonly documented fungal pathogen. We report two cases of infection resulting from C. kefyr in our institution. The two patients had underlying disease states and drug therapies that increased the likelihood of developing an immunocompromised state. The C. kefyr isolates obtained from both patients were susceptible to amphotericin B, fluconazole, and itraconazole. Both patients had resolution of infection, one after receiving treatment with amphotericin B and the other with voriconazole.

Topics: Adult; Amphotericin B; Antifungal Agents; Budd-Chiari Syndrome; Candidiasis; Colonic Neoplasms; Female; Humans; Male; Middle Aged; Treatment Outcome

Fungal urinary tract infections are commonly encountered in the hospitalized neonate. Although these infections most commonly take the form of cystitis, the infection may be complicated by the formation of fungal bezoars, with subsequent urinary tract obstruction. In certain cases, endosurgical debulking or extraction of the fungal bezoar may be necessary. This is particularly challenging in neonates due to their often-compromised physiologic state and small size. We report a case of a premature infant with bilateral obstructing renal fungal bezoars in whom a percutaneous catheter-based thrombectomy system was used successfully to debulk the fungal burden.

Topics: Amphotericin B; Antifungal Agents; Bezoars; Candida albicans; Candidiasis; Catheterization; Humans; Hydronephrosis; Infant, Newborn; Infant, Premature; Kidney; Nephrostomy, Percutaneous; Thrombectomy; Ultrasonography; Urinary Tract Infections

Topics: Abscess; Amphotericin B; Antifungal Agents; Candidiasis; Cataract Extraction; Eye Infections, Fungal; Female; Fluconazole; Fungemia; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Lens Diseases; Male; Vitrectomy

Conventional antifungal therapy for fungal endocarditis has been associated with a poor cure rate. Therefore, combined medical and surgical therapy has been recommended. However, new potent antifungal agents, such as echinocandins, could increase the medical options and, in some cases, avoid the need for surgery. We report a case of Candida endocarditis treated successfully without valve replacement with intravenous liposomal amphotericin B (total dose, 4 g) and intravenous caspofungin (a 100-mg loading dose followed by 50 mg per day for 8 weeks) as induction therapy and intravenous caspofungin (100 mg 3 times per week for 12 weeks) as maintenance therapy.

Topics: Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Drug Therapy, Combination; Echinocandins; Endocarditis; Female; Humans; Lipopeptides; Peptides, Cyclic

Topics: Adult; Amphotericin B; Antifungal Agents; Brain Abscess; Candida albicans; Candidiasis; Caspofungin; Echinocandins; Endocarditis; Fluconazole; Heart Valve Prosthesis; Humans; Lipopeptides; Male; Peptides, Cyclic; Treatment Failure

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cohort Studies; Female; Fungemia; Gestational Age; Humans; Incidence; Infant, Newborn; Intensive Care Units, Neonatal; Male; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sex Distribution; Survival Analysis; United Arab Emirates

Time-kill and postantifungal effect (PAFE) of amphotericin B, caspofungin, fluconazole, and voriconazole were determined against clinical isolates of Candida guilliermondii, Candida kefyr, and Candida lusitaniae. Azoles displayed fungistatic activity and no measurable PAFE, regardless of the concentration tested. Amphotericin B and caspofungin demonstrated concentration-dependent fungicidal activity, although amphotericin B only produced a significant dose-dependent PAFE against all isolates tested.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Colony Count, Microbial; Echinocandins; Fluconazole; Hematologic Neoplasms; Humans; Kinetics; Lipopeptides; Microbial Sensitivity Tests; Models, Biological; Peptides, Cyclic; Pyrimidines; Triazoles; Voriconazole

Cerebrovascular stroke due to Candida (C.) parapsilosis native valve endocarditis (NVE) is rarely reported. Herein, we report a 53-year man with C. parapsilosis NVE and acute ischemic stroke. Diabetes mellitus and recent dental manipulation were the preceding events. Cranial magnetic resonance imaging study revealed occlusion of left common carotid artery, and infarcts of the pons and territory of the branch of left middle cerebral artery. With a total of 4,051 mg amphotericin B therapy and aortic valve replacement, the patient survived with right hemiplegia and dysarthria. In the English literature, there have been 12 patients with C. parapsilosis NVE including our patient over the past 25 years. Intravenous drug abuse was the most common predisposing factor for this infective disorder, followed by hematological malignancy and central venous catheterization. Fever and ischemic phenomenon of lower legs were the common clinical manifestations. Cerebrovascular stroke was present only in our case. Of these 12 patients, one administered fluconazole and miconazole therapy died, while 11 with amphotericin B therapy and one patient with fluconazole monotherapy survived.

Topics: Amphotericin B; Antifungal Agents; Aortic Valve; Brain; Candidiasis; Diabetes Complications; Endocarditis; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Radiography; Stroke; Tooth Extraction

This study was done to determine whether high dose AmBisome (4-20 mg/kg), given intermittently, could reduce the frequency of dosing needed to treat murine systemic candidiasis when compared with conventional daily treatment.. Mice were immunosuppressed with cyclophosphamide every 3 days, beginning day -3 before challenge with log(10) 5.0 cfu Candida albicans. Treatment was begun 48-72 h post-challenge with daily or intermittent dose regimens of AmBisome, followed by determination of kidney cfu for up to 1 month post-treatment.. A single AmBisome dose of 4 mg/kg was as effective as four daily, 1 mg/kg treatments. A total of 8 mg/kg, given as 4 mg/kg on days 2 and 4, or as 5 mg/kg on day 2 followed by 1 mg/kg on days 3, 4, and 5, also produced comparable efficacy. While 20 mg/kg given day 2, 4 and 6 post-challenge as a 1 week loading dose, followed by one 10 mg/kg treatment on day 13, decreased the fungal burden by up to 5 logs compared with controls (log(10) 2.3 cfu/g and log(10) 7.5 cfu/g, respectively), 20 mg/kg given Monday, Wednesday and Friday for 5 weeks, reduced the fungal burden to undetectable levels (i.e. log(10) 1.0 cfu).. Significant reduction or clearance of kidney cfu, following intermittent, high dose AmBisome treatment, indicated that non-daily dosing regimens could be successfully used instead of conventional daily dosing to treat established C. albicans infection in immunosuppressed mice.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Colony Count, Microbial; Disease Models, Animal; Drug Administration Schedule; Female; Immunocompromised Host; Kidney; Liposomes; Mice; Mice, Inbred C57BL; Treatment Outcome

The performance of the Etest using Mueller-Hinton agar supplemented with glucose (2%) and methylene blue (0.5 microg/ml) (MH-GMB) for amphotericin B susceptibility testing of 4,936 isolates of Candida spp. was assessed against that of Etest using RPMI agar with 2% glucose (RPG). MICs were determined by Etest in both media for all 4,936 isolates and were read after incubation for 48 h at 35 degrees C. The Candida isolates included C. albicans (n = 2,728), C. glabrata (n = 722), C. parapsilosis (n = 666), C. tropicalis (n = 528), C. krusei (n = 143), C. lusitaniae (n = 54), C. guilliermondii (n = 39), C. pelliculosa (n = 17), C. kefyr (n = 15), C. rugosa (n = 11), C. dubliniensis (n = 5), C. zeylanoides (n = 4), C. lipolytica (n = 3), and C. famata (n = 1). The Etest results with MH-GMB correlated well with those with RPG. Overall agreement was 92.9%, and agreements for individual species were as follows: C. lusitaniae, 98.1%; C. albicans, 95.1%; C. glabrata, 94.3%; C. krusei, 91.6%; C. parapsilosis, 86.6%; and C. tropicalis, 86.4%. The Etest method using MH-GMB appears to be a useful method for determining amphotericin B susceptibilities of Candida species.

Topics: Agar; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Culture Media; Glucose; Humans; Methylene Blue; Microbial Sensitivity Tests

To establish a novel strategy for the control of fungal infection, we examined the antifungal and neutrophil-activating activities of antimicrobial peptides. The duration of survival of 50% of mice injected with a lethal dose of Candida albicans (5 x 10(8) cells) or Aspergillus fumigatus (1 x 10(8) cells) was prolonged 3 to 5 days by the injection of 10 microg of peptide 2 (a lactoferrin peptide) and 10 microg of alpha-defensin 1 for five consecutive days and was prolonged 5 to 13 days by the injection of 0.1 microg of granulocyte-monocyte colony-stimulating factor (GM-CSF) and 0.5 microg of amphotericin B. When mice received a combined injection of peptide 2 (10 microg/day) with amphotericin B (0.5 microg/day) for 5 days after the lethal fungal inoculation, their survival was greatly prolonged and some mice continued to live for more than 5 weeks, although the effective doses of peptide 2 for 50 and 100% suppression of Candida or Aspergillus colony formation were about one-third and one-half those of amphotericin B, respectively. In vitro, peptide 2 as well as GM-CSF increased the Candida and Aspergillus killing activities of neutrophils, but peptides such as alpha-defensin 1, beta-defensin 2, and histatin 5 did not upregulate the killing activity. GM-CSF together with peptide 2 but not other peptides enhanced the production of superoxide (O2-) by neutrophils. The upregulation by peptide 2 was confirmed by the activation of the O2- -generating pathway, i.e., activation of large-molecule guanine binding protein, phosphatidyl-inositol 3-kinase, protein kinase C, and p47phox as well as p67phox. In conclusion, different from natural antimicrobial peptides, peptide 2 has a potent neutrophil-activating effect which could be advantageous for its clinical use in combination with antifungal drugs.

Topics: alpha-Defensins; Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Candida albicans; Candidiasis; Cells, Cultured; Female; Lactoferrin; Mice; Neutrophil Activation; Peptides; Signal Transduction

A broth microdilution method was used for testing amphotericin B against 33 clinical isolates of Candida tropicalis. All isolates were in vitro susceptible to the polyene (MIC [minimal inhibitory concentration] < or = 1.0 microg/mL). However, when the isolates were cultured in a medium containing amphotericin B at a concentration of 1.5 microg/mL, a wide interstrain variation of growth rate was observed. Five isolates (15%) proved to be highly tolerant to the drug and grew at a frequency ranging from 1 x 10(-1) to 2 x 10(-2). Twenty-three isolates (70%) grew at a frequency ranging from 1 x 10(-5) to 1 x 10(-8). The remaining five isolates (15%) failed to grow in drug-containing medium. In general, this growth variation was not associated with amphotericin B MICs displayed by the single isolates. In addition, the strains grown in drug-containing medium did not represent amphotericin B-resistant mutants, as shown by the maintenance of MICs similar to those of their respective parent isolates. Killing experiments conducted in selected isolates confirmed a variation of fungicidal activity of amphotericin B. To see whether this phenomenon was associated with a variation of amphotericin B response in vivo, we established an experimental model of systemic murine candidiasis in CD1 mice by intravenous injection of cells belonging to Candida tropicalis 3147 (growth rate at a frequency of 1 x 10(-1) in amphotericin B medium) and Candida tropicalis 4055 (no growth). Low (0.3 mg/kg/day) and high (1 mg/kg/day) doses of amphotericin B were both effective at reducing the fungal burdens in the kidneys of mice infected with either strain (p, 0.01 to 0.02). However, whereas the burden of mice infected with isolate 3147 and treated with the polyene at 0.3 mg/kg/day was reduced by 1.2 +/- 0.25 (mean +/- standard deviation) log10 cfu/g compared to untreated mice, the same dosing regimen yielded a burden reduction of 2.6 +/- 0.07 log10 cfu/g in mice infected with isolate 4055 (p < 0.001). Similarly, amphotericin B at 1 mg/kg/day yielded a burden reduction of 1.8 +/- 0.20 vs. 2.5 +/- 0.30 log10 cfu/g in mice infected with isolates 3147 and 4055, respectively (p < 0.001). Our data revealed a variable pattern of tolerance to amphotericin B among isolates of Candida tropicalis and showed that this phenomenon might influence the rate of organ clearance during therapy.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida tropicalis; Candidiasis; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Immunosuppression Therapy; Male; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests

Groups of mice infected intravenously with Candida albicans were treated intraperitoneally with amphotericin B, caspofungin, or fluconazole, starting at intervals before and after challenge. Survival was longest and tissue burdens were most reduced with early treatment, and survival times fell proportionately as treatment was delayed, reinforcing clinical recommendations for the earliest possible initiation of antifungal therapy.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Candidiasis; Caspofungin; Colony-Forming Units Assay; Echinocandins; Female; Fluconazole; Injections, Intraperitoneal; Lipopeptides; Mice; Mice, Inbred BALB C; Peptides, Cyclic; Survival Analysis; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Cross Infection; Disease Outbreaks; Dose-Response Relationship, Drug; Drug Administration Schedule; Hospital Units; Humans; Ireland; Liposomes; Mycoses; Stem Cell Transplantation; Treatment Outcome

Fungal infections are an important complication of lung transplantation, but no controlled studies of their management have been performed. Knowledge of actual anti-fungal strategies may aid in the design of future prospective studies.. Thirty-seven of 69 active lung transplant centers, accounting for 66% of all US lung transplantations, responded to our survey. The survey focused on fungal surveillance, pre- and post-transplant prophylaxis, and approach to fungal colonization.. The median number of lung transplantations performed by the centers in 1999 was 14 per year (range, 1-52), and median time that centers were in in operation was 9 years (range, 2-15 years). Seventy percent of centers had a transplant infectious diseases specialist. Pre-transplant fungal surveillance was performed by 81% of centers, with 67% of these surveying all patients and the remainder surveying only sub-sets of patients. Seventy-two percent of all centers started anti-fungal treatment if Aspergillus spp were isolated before transplantation. Itraconazole was the preferred agent (86%). After transplantation, 76% of centers gave anti-fungal prophylaxis, although 24% of these did so only in selected patients. Prophylactic agents in order of preference were inhaled amphotericin B (61%), itraconazole (46%), parenteral amphotericin formulations (25%), and fluconazole (21%); many centers used more than 1 agent. Prophylaxis was initiated within 24 hours by 71% and within 1 week by all centers. Median duration of prophylaxis was 3 months (range, <1 month-lifetime). All 37 centers used anti-fungal therapy if colonization with Aspergillus spp was detected for a median duration of 4.5 months. Itraconazole was the preferred agent. Only 59% of centers treated patients colonized with Candida spp. In a statistical analysis, centers with larger volumes were less likely to treat pre-transplant colonization with Candida spp but more likely to use agents other than itraconazole for post-transplant colonization with Aspergillus spp. Only 14% of centers engaged in any anti-fungal research at the time of the survey.. The majority of surveyed lung transplant programs actively manage fungal infection with prophylaxis or pre-emptive therapy, despite the absence of controlled trials. This survey may provide an impetus and a basis for designing prospective studies.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bronchoscopy; Candidiasis; Health Care Surveys; Humans; Itraconazole; Lung Diseases, Fungal; Lung Transplantation; Opportunistic Infections; Premedication; United States

In the present study, we have evaluated prophylactic role of various immunomodulators viz. lipopolysachharide, protein A and tuftsin to impart protection against experimental candidiasis in leukopenic mice. Both free as well as liposomised form of nystatin was not effective enough in offering complete cure against less susceptible isolate of Candida albicans (JNMCR) infection in immunodebilitant mice. Interestingly, the pretreatment of leukopenic mice with immunomodulators before challenging them with C. albicans increased therapeutic efficacy of the nystatin against systemic candidiasis. Efficacy of the treatment was evaluated on the basis of survival of the animals as well as fungal load in systemic circulation and various organs viz. liver, kidney, spleen and lungs of the treated animals.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Drug Compounding; Drug Resistance, Fungal; Female; Immunologic Factors; Intercalating Agents; Kidney; Leukopenia; Lipopolysaccharides; Liposomes; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Nystatin; Staphylococcal Protein A; Tuftsin

The ability of the novel antifungal cyclic hexalipopetide A-192411 to treat fungal infections in rodents is presented. Efficacy was demonstrated against Candida albicans as both prolonged survival of systemically infected mice and clearance of viable yeasts from kidneys. The efficacy of A-192411, administered intraperitoneally, was equivalent to amphotercin B at a 4-fold lower dose by weight in the systemic candidiasis models in mice, while the efficacy of A-192441 administered intravenously was equivalent to amphotercin B by weight in the Candida pyelonephritis model in rats. A-192411 also slightly prolonged the survival of immunocompromised mice infected systemically with Aspergillus fumigatus.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Candida albicans; Candidiasis; Drug Resistance, Fungal; Immunocompromised Host; Kidney; Mice; Oligopeptides; Rats; Survival Analysis

Topics: Adolescent; Amphotericin B; Antifungal Agents; Aqueous Humor; Candida albicans; Candidiasis; Combined Modality Therapy; Eye Infections, Fungal; Female; Fungemia; Heart Transplantation; Humans; Iridocyclitis; Iris; Lens, Crystalline; Vitrectomy

Two consensus conferences taking place in the United States and Spain were organized to optimize diagnosis and treatment of Candida spp. infections. Among other results, clinical scenarios in which early prescription of antifungal agents is indicated were identified.. To determine the criteria followed by physicians for prescribing antifungal agents in critically ill patients in our country and to investigate adherence to the guidelines proposed by the consensus conferences.. A questionnaire was designed and directed to 4th- and 5th-year residents in intensive care medicine and to specialists in intensive care with training in infectious diseases or other medical areas. Four case reports for which expert consensus indicates early antifungal treatment were included in the questionnaire; 1) recurrent peritonitis secondary to perforation of the digestive tract, with mixed flora including fungi; 2) persistent febrile syndrome in a patient with multiple mucosal fungal colonizations treated with broad-spectrum antibiotics; 3) candiduria and pyuria in a febrile patient; and 4) candidemia.. A total of 135 questionnaires from 45 different ICUs were returned (60% response rate). In the candidemia and fungal peritonitis examples, early treatment with antifungal agents was indicated in 100% and 85.9% of responses, respectively, whereas for sepsis with multifocal candidiasis and candiduria associated with pyuria and fever, early treatment was prescribed in only 41.5% and 55.6% of responses, respectively. There were no significant differences in response with regard to degree of training of the physicians surveyed. Fluconazole prescription predominated, mainly at doses of 400 mg/day, in mixed peritonitis, disseminated candidiasis and candiduria, whereas amphotericin B lipid formulations were preferentially indicated in cases of candidemia. Antifungal treatment (early or late) was prescribed in all responses for candidemia, in 95.5% for mixed peritonitis (fungi and bacteria), in 79.5% for multifocal candidiasis in patients with persistent sepsis, and in 77.9% for candiduria with fever and pyuria.. Adherence to recommendations from the consensus conferences was high among intensive medicine specialists, with no differences according to level of training in infectious diseases.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Case Management; Consensus Development Conferences as Topic; Critical Care; Data Collection; Drug Utilization; Fever; Fluconazole; Fungemia; Guideline Adherence; Humans; Internship and Residency; Intestinal Perforation; Mycoses; Peritonitis; Practice Guidelines as Topic; Practice Patterns, Physicians'; Spain; Surveys and Questionnaires; Urinary Tract Infections

Due to the increase of the immunocompromised population, mucosal and systemic infections caused by Candida glabrata, formerly known as Torulopsis glabrata, have shown a recent significant increase. We present a case of C. glabrata vertebral osteomyelitis which required repeated surgical therapy, a complete L2 and L3 corporectomy and more than one year of hospitalisation to complete healing. We compare this case to eight previously reported cases outlining the features of C. glabrata spinal osteomyelitis, including symptoms, diagnosis, treatment, evolution and outcome. According to the case presented and in review of the literature, we believe that in the absence of abscess and neurologic symptoms, medical treatment should be initiated with close clinical, laboratory and radiologic follow-up. An unfavorable evolution of these parameters should be an indication for aggressive and, if necessary, repeated surgical intervention in association with an antifungal treatment.

Topics: Amphotericin B; Candida glabrata; Candidiasis; Fluconazole; Humans; Lumbar Vertebrae; Male; Osteomyelitis; Radiography

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Caspofungin; Drug Resistance, Fungal; Echinocandins; Fluconazole; Humans; Lipopeptides; Peptides; Peptides, Cyclic

Minimum fungicidal concentrations (MFCs) of amphotericin B were obtained for 165 bloodstream isolates (104 Candida parapsilosis, 14 C.glabrata, 13 C.tropicalis, 15 C.krusei, and 19 C.albicans) and 36 C.dubliniensis from oropharyngeal infections. Minimum inhibitory concentrations (MICs) were determined by the M27-A microdilution method. MFCs (> or =99.9% killing) were obtained following MIC determination (inoculum size, 10(4) CFU/ml) by seeding the entire volume of all clear wells. The best fungicidal activity was for C. albicans, (MFC90 1 microg/ml) and the lowest for C.parapsilosis, C.tropicalis and C.glabrata (MFC90 16 microg/ml). Although MFCs were > or =16x MIC for some isolates, including C. glabrata, the overall MFCs were > or =2x MICs. However, major differences between MICs and MFCs were observed for C.parapsilosis and C.dubliniensis (3.8% and 8.9%, respectively, were tolerant: MFC > or =32MIC). MFCs for C.tropicalis and C. glabrata were > or =2 microg/ml. By this more stringent method we found substantial differences from those previously reported between amphotericin B MIC and MFCs for Candida spp.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Colony Count, Microbial; Female; Fungemia; Humans; Male; Microbial Sensitivity Tests; Sensitivity and Specificity

Candida colliculosa, which grew in blood cultures of a 71-year-old retired man with fever of unknown origin that had lasted for 7 months, in conjunction with transthoracic echocardiography, demonstrating a 20-mm vegetation, superior to the tricuspid valve, herniating into the right atrial cavity. The finding led to the diagnosis of fungal endocarditis. Fluconazole, 600 mg daily, was commenced for 8 days; followed by amphotericin B, 1 mg/kg daily. On the fourth day of the amphotericin B treatment, the patient underwent replacement of the infected tricuspid valve. Even though the initial postoperative period was relatively uncomplicated, the patient died after a gross aspiration on the 67th day of his hospital stay, despite aggressive cardiovascular support and antimicrobial therapy. This is the first report of a native tricuspid valve fungal endocarditis due to C. colliculosa or Torulaspora delbrueckii, which is not known to be a human pathogen.

Topics: Aged; Amphotericin B; Candida; Candidiasis; Endocarditis; Fluconazole; Humans; Male; Tricuspid Valve

Children with acute lymphoblastic leukemia (ALL) are at risk for serious electrolyte abnormalities. The authors report their experience in managing a child with ALL who developed severe hyperphosphatemia as a consequence of a large exogenous load of phosphorus from high-dose liposomal amphotericin B. Health care providers need to recognize this potentially life-threatening complication of liposomal amphotericin B, since early detection and intervention can prevent significant morbidity.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Calcium Carbonate; Candidiasis; Cellulitis; Child; Drug Carriers; Female; Headache; Humans; Hyperparathyroidism, Secondary; Immunocompromised Host; Itraconazole; Liposomes; Mucormycosis; Orbital Diseases; Parathyroid Hormone; Phosphates; Phosphatidylcholines; Phosphatidylglycerols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Seizures; Sinusitis; Vitamin D

The activity of caspofungin (CFG) combined with amphotericin B (AMB) against azole-resistant Candida albicans was evaluated in vitro (chequerboard) and in vivo (murine). CFG+AMB resulted in positive interactive effects in vitro (fractional inhibitory concentration index 0.75). Compared with untreated controls, CFG+AMB prolonged mouse survival (P = 0.006) and compared with AMB alone, CFG+AMB prolonged mouse survival (P = 0.36); however, the latter difference was not significant. CFG+AMB treatment significantly reduced kidney cfu compared with untreated controls and CFG-treated groups (P < or = 0.05 for both comparisons). In addition, this combination reduced brain cfu significantly compared with untreated controls and AMB-treated mice (P = 0.005 and 0.05, respectively).

Topics: Amphotericin B; Animals; Azoles; Candida albicans; Candidiasis; Caspofungin; Drug Resistance, Fungal; Drug Therapy, Combination; Echinocandins; Humans; Lipopeptides; Male; Mice; Mice, Inbred BALB C; Peptides; Peptides, Cyclic

The isolation of Candida sp in nosocomial infections is on the increase and over the past 10 years many guidelines for "good" practices and recommendations have been published on the modalities for the management of systemic candidiasis. The aim of this paper was to assess the habits in the intensive care units in this domain in France.. A transversal survey on the habits was conducted from March to May 2001, using a questionnaire mailed to 200 intensive care units.. One hundred eighty questionnaires (surgical reanimation: 12%, medical: 18%, medico-surgical: 70%) out of 200 (92.5%) were returned. The indirect diagnostic examinations: serology, search for antigenemia and PCR (Polymerase Chain Reaction) were never used in 21, 35 and 65% of cases. The systematic search for colonisation (a mean of 4 areas sampled) was conducted in all the patients by 19% of the investigators, in some patients by 53%, and never by 28%. An antifungal treatment was prescribed: in the presence of a positive haemoculture alone, once out of twice if the sample had been taken from a central catheter and in 2 cases out of 3 when the sample was peripheral. It was prescribed 6 times out of 10 after isolation of Candida sp following surgery or on needle aspiration of an intra-abdominal abscess, varyingly in the case of cadiduria, isolation of a Candida sp in a broncho-pulmonary sample or in abdominal draining and positive culture of a catheter, depending on the intensity of the colonisation, the severity of the clinical picture and the presence of factors of risk for Candida infection. It is still prescribed empirically depending on the same elements and the absence of explanation for worsening. When faced with candidemia in a non-neutropenic patient, a central catheter is not changed in 18% of cases. Depending on the microbiology, fluconazole is prescribed in: the identification of yeast without further precision (78% of cases), Candida sp without further precision (86% of cases), Candida non albicans without further precision (57% of cases), C. albicans (93% of cases), Candida non albicans other than C. krusei and C. glabrata (62% of cases), C. glabrata (36% of cases) with an increase in dose in 1 out of 2 cases. In the presence of C. glabrata or C. krusei, amphotericin B is the choice in respectively 51 and 75% of cases. To adapt the treatment.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; Cross-Sectional Studies; Equipment Contamination; Female; Fluconazole; France; Fungemia; Humans; Incidence; Intensive Care Units; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Risk Factors

A 54-year-old farmer with moderate mitral valve regurgitation was admitted to hospital because of suspected infective endocarditis.. Echocardiography revealed a large mitral valve vegetation as the source of multifocal septic emboli to the central nervous system, spleen, mesenteric and femoro-popliteal arteries, eyes, and kidneys. Eventually an embolus removed from the femoro-popliteal artery and vegetations on the replaced mitral valve grew C. albicans.. Despite treatment with amphotericin B and valve replacement the patient died of septicemia due to E. coli.. Endocarditis due to C. albicans is commonly associated with severe complications. Diagnosis of this rare disease is often delayed because of negative blood cultures. Large cardiac vegetations and embolization of major arterial vessels should raise the suspicion of fungal endocarditis.

Topics: Amphotericin B; Candida albicans; Candidiasis; Echocardiography; Embolism; Endocarditis; Escherichia coli Infections; Fatal Outcome; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Sepsis

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Drug Therapy, Combination; Fluconazole; Fungemia; Humans

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Candida albicans; Candidiasis; Chemoprevention; Drug Resistance, Microbial; Female; Fluconazole; Fungemia; Humans; Leukemia; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia

Systemic fungal infections have high mortality, and therapy is often toxic. Caspofungin acetate, a new antifungal agent with minimal toxicity, may provide a better alternative to typical therapy for Candida krusei.. Case report.. Multidisciplinary intensive care unit (ICU) of a community teaching hospital.. A 22-yr-old male with acute lymphoblastic leukemia and Candida krusei fungemia failed therapy with fluconazole and amphotericin B.. Caspofungin acetate given intravenously as a 70-mg loading dose, followed up by 50 mg daily along with standard ICU care.. Survival without toxicity from therapy.. Efficacy of caspofungin acetate in a patient with life-threatening Candida Krusei infection.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candida; Candidiasis; Caspofungin; Echinocandins; Fluconazole; Fungemia; Humans; Infusions, Intravenous; Lipopeptides; Male; Neutropenia; Opportunistic Infections; Peptides; Peptides, Cyclic; Pleural Effusion; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tomography, X-Ray Computed; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Combined Modality Therapy; Fluconazole; Flucytosine; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Kidney; Male; Nephritis; Urologic Surgical Procedures

Fungal prosthetic valve endocarditis is particularly serious, and is usually a result of nosocomial candidaemia. This report describes a patient with Candida albicans prosthetic valve endocarditis in whom surgery was believed to be contraindicated. After 45 d of amphotericin B, treatment was continued with fluconazole daily with a follow-up of 16 months, with no recurrent or adverse effects.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Drug Therapy, Combination; Endocarditis; Fluconazole; Heart Valve Prosthesis; Humans; Male; Prognosis; Prosthesis-Related Infections; Risk Assessment; Treatment Outcome

Oropharyngeal candidiasis (OPC) and esophageal candidiasis (EPC) are frequent complications in AIDS patients. The use of Fluconazole, an effective and a low toxicity drug, has been associated to the emergency of secondary resistant strains. For this reason, in vitro antifungal susceptibility tests are necessary to predict a therapeutic failure. Etest is an easy to perform alternative test, that has showed a good agreement with the broth microdilution reference method (NCCLS, document M27-A).. To measure the susceptibility of C. albicans isolates from AIDS patients complicated with OPC and EPC to Amphotericin B (AmB) and Fluconazole (Flu) using Etest.. Twenty strains from 20 AIDS patients were studied. AmB was tested in RPMI 1640 agar and Flu in Casitone agar.. All studied strains showed minimal inhibitory concentrations (MICs) < 1 mg/mL for AmB. A highly resistant strain to Flu (> 256 mg/mL) was isolated from a patient previously treated with Flu.. In AIDS patients with OPC and EPC, the susceptibility to Flu of the isolates should be screened, to detect resistant strains. Etest is a reliable alternative in these cases, for laboratories that cannot use the reference method.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Candidiasis, Oral; CD4 Lymphocyte Count; Drug Resistance, Fungal; Esophageal Diseases; Female; Fluconazole; Humans; Male; Microbial Sensitivity Tests; Pharyngeal Diseases

In the present study, we evaluated tuftsin bearing nystatin liposomes for their potential against an isolate of Candida albicans (C. albicans) showing less in vivo susceptibility to amphotericin B (Amp B). The liposomised-Amp B in higher doses was found to be effective in elimination of less susceptible strain of C. albicans (C. albicans JMCR) in Balb/c mice, but may not be recommended due to toxicity constraints. On the other hand, liposomal nystatin was shown to possess higher efficacy as compared to that of Amp B, and was pertinent in treatment of C. albicans JMCR strain. The data of present work reveals that the incorporation of nystatin in tuftsin-bearing-liposomes results in a significant increase in its efficacy against experimental murine candidiasis. Interestingly, the pre-treatment of animals with liposomised-tuftsin prior to challenge with C. albicans infection was more effective in elimination of the pathogen from host and shows an advantage in prophylactic perspectives.

Topics: Adjuvants, Immunologic; Amphotericin B; Animals; Antibiotic Prophylaxis; Antifungal Agents; Candida albicans; Candidiasis; Cholesterol; Chromatography, High Pressure Liquid; Female; Liposomes; Mice; Mice, Inbred BALB C; Nystatin; Phosphatidylcholines; Tuftsin

To study the toxicity and activity of two new amphotericin B formulations: poly(epsilon-caprolactone) nanospheres coated with poloxamer 188 (AmB-NP) and mixed micelles with the same surfactant (AmB-MM).. The toxicity of these formulations was evaluated in erythrocytes, J774.2 macrophages and LLCPK1 renal cells, as well as in mice. Activity was determined in clinical isolates and in neutropenic mice. Mice were made neutropenic with 5-fluorouracil, infected with Candida albicans and treated with the antifungal formulations for three consecutive days. AmB association in cells and accumulation in kidneys and liver of animals was quantified by HPLC.. Both formulations decreased between 8- and 10-fold the MIC of the polyene against clinical isolates of C. albicans. However, their activity was lower than or equal to that of AmB-deoxycholate when it was assessed against C. albicans-infected macrophages. When given as a single intravenous dose in mice, AmB-MM and AmB-NP had an LD50 of 9.8 and 18.6 mg/kg, respectively, compared with 4 mg/kg for AmB-deoxycholate. Comparison of residual infection burdens in the liver and kidneys showed that AmB-deoxycholate (0.5 mg/kg) was more effective and faster in eradicating yeast cells than polymeric formulations. This fact can be related to a lower AmB accumulation inside macrophages and in liver and kidneys (about 1.5 mg drug/g tissue) of mice, compared with those detected for AmB-deoxycholate (4 mg drug/g). Overall, the efficacy of these formulations at 2 mg/kg was equal to that of AmB-deoxycholate at 0.5 mg/kg.. AmB-MM and AmB-NP decreased the in vivo antifungal activity of AmB, and higher concentrations were therefore necessary to obtain a similar therapeutic effect. However, these higher concentrations were achievable owing to the reduced toxicity of these formulations.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Caproates; Cells, Cultured; Chemical Phenomena; Chemistry, Physical; Drug Carriers; Erythrocytes; Excipients; Hemoglobins; Humans; In Vitro Techniques; Lactones; Macrophages; Male; Mice; Micelles; Microspheres; Neutropenia; Particle Size; Poloxamer; Potassium; Surface-Active Agents; Survival Analysis

Occurrence of neonatal circulatory collapse imposes effective differential diagnosis and expeditious therapeutic intervention. We report a case of neonatal cardiogenic shock, caused by a massive intra-cardiac fungal vegetation.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cardiopulmonary Bypass; Ductus Arteriosus, Patent; Echocardiography, Transesophageal; Female; Flucytosine; Humans; Infant, Newborn; Shock, Cardiogenic; Tricuspid Valve; Ventricular Outflow Obstruction

Solubilization of amphotericin B (AMB) by dioctadecyldimethylammonium bromide (DODAB) bilayer fragments inspired this evaluation of its in vivo activity from survival and tissue burden experiments against systemic candidiasis in a mouse model. AMB (< or =0.1 g/L) was simply added to a DODAB powder dispersion in water (10 g/L) previously prepared by sonication in the absence of organic solvents. The AMB aggregation state was evaluated from UV-visible light absorption and dynamic light scattering for aggregate sizing. AMB was stabilized by the DODAB bilayer fragments in its monomeric form, mixing of AMB and DODAB dispersion in pure water causing disappearance of large water-insoluble drug aggregates. From survival experiments, both the bilayer, DODAB/AMB, and the traditional deoxycholate/AMB formulation (DOC/AMB) had identical effect when given by the same route at the same dose of 0.4 mg/kg/day given intraperitoneally for 10 days. From spleen and kidneys tissue burden experiments, similar efficacy of both preparations in reducing tissue cfu counts was obtained. In summary, DODAB/AMB was as effective as DOC/AMB for treating systemic candidiasis in a mouse model.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Chemical Phenomena; Chemistry, Pharmaceutical; Chemistry, Physical; Colloids; Colony Count, Microbial; Dose-Response Relationship, Drug; Drug Stability; Lipid Bilayers; Mice; Microbial Sensitivity Tests; Particle Size; Quaternary Ammonium Compounds; Scattering, Radiation; Spectrophotometry, Ultraviolet; Survival Analysis

Hepatosplenic microabscesses secondary to invasion by various organisms may result in life-threatening conditions, especially in patients with cancer. Whether these patients should continue ongoing cytotoxic therapy, which might result in neutropenia, with the risk of progressive abscess formation or fungemia, remains a dilemma. We report five cases of pediatric acute leukemia with hepatosplenic microabscesses in children aged 4 years to 18 years. These patients presented with prolonged fever and neutropenia after antineoplastic chemotherapy, followed by abdominal pain, hepatosplenomegaly and hepatic dysfunction. Abdominal ultrasound and computed tomography (CT) or magnetic resonance imaging (MRI) demonstrated multiple small lesions compatible with hepatosplenic candidiasis in all of the patients. Cultures, including blood or stool cultures, were positive in only two cases. Treatment with intravenous antifungal agents, including amphotericin B, liposomal amphotericin B, and/or fluconazole were successful in two cases. These two patients remained event-free and survived for more than 24 months (20 months and 22 months after infection was diagnosed). The duration of systemic antifungal medication administration ranged from 3 months to 22 months. The serial image examinations revealed drastic reductions in small residual lesions in the two patients who survived the longest. The major issues for these patients were how long the antifungal therapy should be administered for, and how to select the optimal drug and dosage to avoid hepatic and renal toxicity. Among our patients, alternative therapy with amphotericin B, liposomal amphotericin B, and fluconazole was used according to the patients' conditions, and the duration of antifungal therapy was determined by clinical manifestations and imaging study changes.

Topics: Abscess; Acute Disease; Adolescent; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Drug Administration Schedule; Humans; Leukemia; Liver Abscess; Male; Splenic Diseases

Candida rugosa has been rarely reported as a human pathogen. We retrospectively evaluated a cluster of Candida rugosa candidemia cases occurring in six hospitalized patients from a tertiary care teaching hospital in São Paulo, Brazil. Genetic relatedness among the six C. rugosa outbreak isolates was characterized by RAPD assay using 3 different 10-mer primers and by pulsed field gel electrophoresis. The source of the outbreak was not identified. All patients had been subjected to invasive medical procedures, including central venous catheterization, surgery or dialysis. Two patients were undergoing amphotericin B therapy prior to the onset of candidemia. The crude mortality rate was very high, despite antifungal therapy. C. rugosa may represent an emerging pathogen associated with invasive medical procedures, able to infect immunocompetent hosts causing serious systemic infection refractory to amphotericin B therapy.

Topics: Age Distribution; Aged; Amphotericin B; Brazil; Candida; Candidiasis; Disease Outbreaks; Drug Resistance, Fungal; Female; Fungemia; Humans; Incidence; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Risk Assessment; Sex Distribution; Survival Rate; Treatment Outcome

Antifungal susceptibilities of 28 Candida albicans isolates and two quality control strains to amphotericin B and fluconazole were determined by flow cytometry and microdilution method. Minimum inhibitory concentrations (MICs) obtained by flow cytometry were compared with the results obtained by The National Committee for Clinical Laboratory Standards Subcommittee (NCCLS) broth microdilution method. The agreement of results (within two dilution) obtained was found as 96 and 93% for amphotericin B and fluconazole, respectively. At least 24 h incubation was required for reading the microdilution assays. Four hours of incubation was required for fluconazole, whereas 2-h incubation was sufficient for amphotericin B to provide MIC by flow cytometry. Results of this study show that flow cytometry provides a rapid and sensitive in vitro method for antifungal susceptibility testing of Candida albicans isolates.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Flow Cytometry; Fluconazole; Fungemia; Humans; Microbial Sensitivity Tests

We evaluated the antifungal susceptibility profile of 200 recent bloodstream isolates of Candida spp. sequentially obtained from patients admitted to five tertiary care hospitals in Brazil. Isolates were identified by classical methods and the antifungal susceptibility profile was determined by the NCCLS microbroth assay method. Candida albicans was the most frequent species (41.5%); followed by C. tropicalis (24%) and C. parapsilosis (20.5%). The frequency of C. glabrata and C. krusei was low (nine and two isolates, respectively). Only three strains were resistant to fluconazole (two C. krusei and one C. glabrata) and only one was resistant to itraconazole (the same C. glabrata strain that was resistant to fluconazole). Two strains were considered susceptible dose-dependent (SDD) to fluconazole and 13 isolates (6.5%) were SDD to itraconazole. Overall, the MIC50 value of non-C. albicans isolates for fluconazole was two dilutions higher than that of C. albicans isolates, and for itraconazole was one dilution higher. Resistance to amphotericin B (MIC > or = 2 microg ml(-1)) was observed in 2.5% of isolates (two strains of C. albicans, two of C. parapsilosis and one of C. krusei). This study showed that episodes of candidemia in Brazilian public hospitals are represented mainly by fluconazole-susceptible non-C. albicans species. This finding is probably related to the low use of fluconazole in these hospitals.

Topics: Amphotericin B; Antifungal Agents; Brazil; Candida; Candida albicans; Candidiasis; Drug Resistance, Fungal; Fluconazole; Fungemia; Humans; Inpatients; Itraconazole; Microbial Sensitivity Tests

Candida krusei is an opportunistic pathogen commonly implicated in urinary tract infections in immunocompromised patients. We present the first case of C. krusei renal cyst infection, occurring in a post-liver and kidney transplant patient with autosomal dominant polycystic kidney disease. Her persistent candiduria and fevers were refractory to prolonged therapy with AmBisome (Fujisawa Pharmaceuticals Co. Ltd., Osaka, Japan). She eventually required bilateral nephrectomies of her native kidneys. Cystic fluid was aspirated from six hemorrhagic and six nonhemorrhagic cysts. Cystic fluid cultures yielded C. krusei. Fluid from the nonhemorrhagic cysts was also analyzed for amphotericin B levels, measured using a bioassay. Free amphotericin B levels in the cysts were lower than the minimal inhibitory concentration for amphotericin B for this organism. We provide the first description of amphotericin B levels in cystic fluid obtained during bilateral nephrectomies.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Female; Humans; Kidney; Kidney Diseases, Cystic; Kidney Transplantation; Liposomes; Liver Transplantation; Middle Aged

The objective of this study was to compare the effectiveness and tolerability of three antifungal preparations, amphotericin B, liposomal amphotericin B (LamB) and amphotericin B colloidal dispersion (ABCD), in the treatment of neonatal Candida bloodstream infection (CBSI).. All patients hospitalized in the neonatal intensive care unit from 1996 to 2000 with CBSI were enrolled. Patients with a serum creatinine concentration of <1.2 mg/dL received amphotericin B, and those with serum creatinine > or =1.2 mg/dL received LamB or ABCD. Complete blood counts, and renal and hepatic function tests were obtained before, during and after treatment; blood cultures were performed daily until three consecutive cultures were negative. If cultures were positive for more than 10 days with clinical signs of fungal infection and/or persistent thrombocytopenia, a second antifungal drug was added.. Fifty-six infants met the study criteria: four term and 52 preterm, including 36 extremely low birth weight infants. Amphotericin B was the initial treatment for 34, LamB for 6 and ABCD for 16 infants. No differences in mortality were found between the three groups. Sterilization of the blood was achieved with amphotericin B in 67.6% of patients, LamB in 83.3% and ABCD in 57.1%, when used as monotherapy; with the addition of a second antifungal agent, success rates were 100%, 83.3% and 92.8%, respectively. There were no differences between the groups in the time to resolution of fungaemia. No patients had immediate local or systemic adverse events and none showed deterioration in renal function.. ABCD and LamB appear to be effective, safe and well tolerated in premature infants with CBSI and renal dysfunction. Larger trials are needed before routine use can be recommended.

Topics: Amphotericin B; Candidiasis; Chemistry, Pharmaceutical; Chi-Square Distribution; Colloids; Female; Fungemia; Humans; Infant, Newborn; Infant, Premature; Liposomes; Male

High-dose (5-7 mg/kg/day) liposomal amphotericin B was evaluated prospectively during the period 1995-2001 in 41 episodes of systemic candidiasis occurring in 37 neonates (36 of the 37 were premature infants with very low birth weights). Median age at the onset of systemic candidiasis was 17 days. Candida spp. were isolated from blood in all patients and from urine, skin abscesses and peritoneal fluid in 6, 5 and 1 neonates, respectively. Candidiasis was due to Candida parapsilosis in 17 cases, Candida albicans in 15 cases, Candida tropicalis in 5 cases, Candida guilliermondii in 2 cases, Candida glabrata in 2 cases and an unidentified Candida sp. in 1 case. Twenty-eight, five and eight infants received 7, 6-6.5 and 5 mg/kg/day, respectively. Median duration of therapy was 18 days; median cumulative dose was 94 mg/kg. Fungal eradication was achieved in 39 of 41 (95%) episodes; median duration of therapy until fungal eradication was 8.7+/-4.5 days. Fungal eradication was achieved after 10.9+/-4.8 days in patients who had received previous antifungal therapy compared to 8.2+/-4.3 days in those treated with liposomal amphotericin B as first-line therapy. One patient died due to systemic candidiasis on day 12 of therapy. High-dose liposomal amphotericin B was effective and safe in the treatment of neonatal candidiasis. Fungal eradication was more rapid in patients treated early with high doses and in patients who received high-dose liposomal amphotericin B as first-line therapy.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cross Infection; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Fungemia; Humans; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Liposomes; Male; Probability; Prospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome

Micafungin sodium (MCFG) is a new lipopeptide antifungal agent of the echinocandin class. MCFG inhibits 1,3-beta-glucan synthesis in C. albicans and A. fumigatus in a non-competitive manner and has antifungal activity against both Aspergillus and Candida species. In neutropenic mouse models of disseminated candidiasis and pulmonary aspergillosis, the efficacy of MCFG was superior to that of fluconazole and itroconazole, but comparable to that of amphotericin B. The efficacy and safety of MCFG were investigated in 70 patients with deep-seated mycosis caused by Candida and Aspergillus species. The overall clinical response rates were 57.1% in aspergillosis and 78.6% in candidiasis. The incidence of adverse events related to micafungin was 17.9 %, and there was no dose-related occurrence of any adverse events. The results from this study indicated that micafungin was effective against aspergillosis and candidiasis, with no tolerability problems.

Topics: Adult; Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus; Candida; Candidiasis; Echinocandins; Fluconazole; Humans; Itraconazole; Lipopeptides; Lipoproteins; Micafungin; Mice; Peptides, Cyclic

Deep-seated Candida infections are strongly associated with mortality and morbidity of patients, and need early diagnosis. The frequency of deep-seated fungal infection has recently been growing. We encountered a tuboovarian abscess caused by Candida glabrata after chemotherapy with an anticancer drug, methotrexate, in a febrile neutropenic patient. The susceptibilities to fluconazole and amphotericin B were 16 and 0.5 micro g/ml, respectively. Although combination therapy of fluconazole and amphotericin B was effective, left salpingectomy was laparoscopically performed because the left adnexal tumor continued to exist asymptomatically after 1 month.

Topics: Abscess; Adult; Amphotericin B; Antifungal Agents; Antimetabolites, Antineoplastic; Candida glabrata; Candidiasis; Diagnosis, Differential; Fallopian Tubes; Female; Fever; Fluconazole; Genital Diseases, Female; Granulocyte Colony-Stimulating Factor; Humans; Hydatidiform Mole; Magnetic Resonance Imaging; Methotrexate; Neutropenia; Pregnancy

Since the 1990s, changing trends have been documented in species distribution and susceptibility to bloodstream infections caused by Candida species in cancer patients. However, few data are available regarding the association between in vitro antifungal susceptibility and outcome of candidemia in this patient population. We therefore evaluated the association of in vitro antifungal susceptibility and other risk factors with failure of initial antifungal therapy in cancer patients with candidemia. Candidemia cases in cancer patients from 1998 to 2001 (n = 144) were analyzed retrospectively along with their in vitro susceptibility to amphotericin B, fluconazole, and itraconazole (National Committee for Clinical and Laboratory Standards M27-A method). Patients were evaluable for outcome analysis if they received continuous unchanged therapy with either fluconazole or amphotericin B for >/=5 days. We excluded cases of mixed candidemia. In vitro susceptibility testing data of the first Candida bloodstream isolate were analyzed. Appropriate therapy was defined as that using an active in vitro antifungal for >/=5 days. For fluconazole susceptible-dose dependent Candida species, we defined appropriate therapy as a fluconazole dose of >/=600 mg/day. The Candida species distribution was 30% Candida albicans, 24% Candida glabrata, 23% Candida parapsilosis, 10% Candida krusei, 9% Candida tropicalis, and 3% other. Overall, amphotericin B was the most active agent in vitro, with only 3% of the isolates exhibiting resistance to it (>1 mg/L). Dose-dependent susceptibility to fluconazole and itraconazole was seen in 13% and 21% of the isolates, respectively, while resistance to fluconazole and itraconazole was seen in 13% and 26%, respectively.Eighty patients were evaluable for outcome analysis. In multivariate analysis, the following factors emerged as independent predictors of failure of initial antifungal therapy: leukemia (p = 0.01), bone marrow transplantation (p = 0.006), and intensive care unit stay at onset of infection (p = 0.02). Inappropriate antifungal therapy, as defined by daily dose and in vitro susceptibility, was not shown consistently to be a significant factor (it was significant in multivariate analysis, p = 0.04, but not in univariate analysis), indicating the complexity of the variables that influence the response to antifungal treatment in cancer patients with candidemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Microbial; Female; Fluconazole; Humans; Itraconazole; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Retrospective Studies; Risk Factors; Treatment Outcome

Invasive fungal infections (IFI) are associated with high mortality in liver transplant recipients. Prevention remains an elusive goal, especially for IFI caused by moulds.. From January 1998, patients who fulfilled four or more variables identified as risk factors for IFI received a cumulative dose of 1-1.5 g of lipid formulations of amphotericin B (L-AmpB; AmBisome or Abelcet). The development of IFI in these patients was compared with historical patients.. Two hundred and eighty liver transplant recipients were analysed over a period of 8 years. In the historical group, IFI were observed in 22 of 131 patients (17%) and invasive aspergillosis in 13 of them (10%). After January 1998, IFI were observed in nine of 149 (6%) (P < 0.01) and invasive aspergillosis in six patients (4%) (P = 0.08). In patients with four or more risk factors (high risk) for IFI, the administration of L-AmpB reduced the risk from 36% to 14% (P = 0.07), and the risk of aspergillosis from 23% to 5% (P = 0.08). Notably, prophylaxis reduced the risk of aspergillosis from 32% to 0% in dialysed patients (P = 0.03). Variables independently associated with IFI in high-risk patients were dialysis [odds ratio (OR) 3.9; 95% confidence interval (CI) 1-16.7] and surgical reintervention (OR 5.4; 95% CI 1.2-24.6), while L-AmpB was a protective factor in this multivariate analysis (OR 0.1; 95% CI 0.02-0.8). The analysis in these high-risk patients was not able to demonstrate an association between the administration of L-AmpB and higher survival.. Selected risk factors are good predictors of IFI in liver transplant recipients. The administration of L-AmpB in high-risk patients is independently associated with a reduction of IFI.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Drug Combinations; Female; Humans; Liver Transplantation; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols; Risk Factors

Topics: Aged; Amphotericin B; Antifungal Agents; Candidiasis; Humans; Male; Prosthesis-Related Infections; Stroke; Ventriculoperitoneal Shunt

To report the clinical picture and outcome of fungal infection of self-sealing wounds in cataract surgery.. Retrospective noncomparative case series.. Seven postoperative cataract patients.. Seven consecutive patients who underwent cataract surgery in different locations in India and developed microbiologically proven fungal infection of the surgical wound were included. All were managed at a tertiary eye care center in India between May 2001 and April 2002.. The data reviewed included patient age, gender, onset of symptoms after surgery, examination findings at the time of onset of symptoms and referral, laboratory workup, treatment, and outcome. The cataract surgeons involved were contacted to determine their cataract practice and to determine any possible breach in the sterile technique.. The median interval to onset of symptoms after cataract surgery was 5.0 days (mean, 5.8 days; range, 3-9 days). The initial diagnoses at the time of onset of symptoms were keratitis (n = 3), scleritis (n = 1), and excessive anterior chamber reaction (n = 3). The last 4 patients were treated with topical and/or systemic corticosteroid therapy before referral. All cases subsequently developed deep keratitis. Specimens for microbiology workup were obtained by scrapings (n = 6), corneoscleral biopsy (n = 4), and anterior chamber paracentesis (n = 4). Organisms identified were Aspergillus flavus (n = 2), Aspergillus terreus (n = 2), Aspergillus spp. (n = 2), and Candida albicans (n = 1). The infection resolved with medical therapy in 2 cases; the final visual acuity was 20/125 in one case and 20/20 in the other case. The infection progressed to endophthalmitis in 5 eyes, resulting in complete loss of vision. The source of infection could not be identified in any case.. Infection of self-sealing tunnel incision for cataract surgery is a diagnostic and therapeutic challenge.

Topics: Aged; Aged, 80 and over; Amphotericin B; Aspergillosis; Candidiasis; Corneal Ulcer; Drug Therapy, Combination; Eye Infections, Fungal; Female; Fluconazole; Humans; Ketoconazole; Male; Minimally Invasive Surgical Procedures; Natamycin; Phacoemulsification; Retrospective Studies; Scleritis; Surgical Wound Infection; Suture Techniques

We report a case of Candida infection after laser in situ keratomileusis (LASIK) and review the literature for reports of post-LASIK fungal infections. Risk factors may include postoperative surgical intervention and extended use of topical steroids.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cornea; Drug Therapy, Combination; Eye Infections, Fungal; Flucytosine; Humans; Keratitis; Keratomileusis, Laser In Situ; Male; Microscopy, Confocal; Middle Aged