amphotericin-b and Fungemia

Ruxolitinib is a novel oral Janus kinase inhibitor that is used for treatment of myeloproliferative diseases. It exhibits potent anti-inflammatory and immunosuppressive effects, and may increase the risk of opportunistic infections. Here, we report a rare case of Cryptococcus neoformans and Mycobacterium haemophilum coinfection in a myelofibrosis patient who was receiving ruxolitinib.. A 70-year-old Thai man who was diagnosed with JAK2V617F-mutation-positive primary myelofibrosis had been treated with ruxolitinib for 4 years. He presented with cellulitis at his left leg for 1 week. Physical examination revealed fever, dyspnea, desaturation, and sign of inflammation on the left leg and ulcers on the right foot. Blood cultures showed positive for C. neoformans. He was prescribed intravenous amphotericin B deoxycholate with a subsequent switch to liposomal amphotericin B due to the development of acute kidney injury. He developed new onset of fever after 1 month of antifungal treatment, and the lesion on his left leg had worsened. Biopsy of that skin lesion was sent for mycobacterial culture, and the result showed M. haemophilum. He was treated with levofloxacin, ethambutol, and rifampicin; however, the patient eventually developed septic shock and expired.. This is the first case of C. neoformans and M. haemophilum coinfection in a patient receiving ruxolitinib treatment. Although uncommon, clinicians should be aware of the potential for multiple opportunistic infections that may be caused by atypical pathogens in patients receiving ruxolitinib.

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Cellulitis; Coinfection; Cryptococcosis; Cryptococcus neoformans; Deoxycholic Acid; Drug Combinations; Fungemia; Humans; Male; Mycobacterium haemophilum; Mycobacterium Infections; Nitriles; Opportunistic Infections; Primary Myelofibrosis; Pyrazoles; Pyrimidines

Cases of invasive Trichosporon infections have increasingly emerged; it is now the second leading cause of yeast bloodstream infections after Candida spp., particularly in the immunosuppressed population, where it often causes breakthrough fungemia with high mortality.. We present a case report of a breakthrough Trichosporon asahii infection in a patient with acute myeloid leukemia and review all of the cases of breakthrough Trichosporon spp. infections published in the literature to date.. We extracted 68 cases of breakthrough Trichosporon spp. infections, wherein 95.5% patients had hematological malignancy, 61.8% of them occurred in the presence of echinocandins, 22% of triazoles, 13.2% of amphotericin and 3% of other combinations of antifungals. The most prevalent manifestation was fungemia (94%); 82.8% of these were associated with the presence of a central venous catheter. The overall mortality was 68.7%; the patients who survived recovered from the neutropenic event.. Invasive trichosporonosis is an acute fatal condition that occurs in immunosuppressed patients, usually under antifungal selective pressure. Typically, neutropenia and its underlying diseases are associated with adverse outcomes.

Topics: Adult; Amphotericin B; Antifungal Agents; Central Venous Catheters; Echinocandins; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Middle Aged; Mortality; Neutropenia; Triazoles; Trichosporon; Trichosporonosis; Voriconazole

Emergent fungal infections are uncommon conditions which frequently lead to death. To our knowledge, only a few cases of invasive infection by Cystobasidium minutum (previously known as Rhodotorula minuta) have been reported. Moreover, several factors are responsible for deep site infections, such as catheter-related fungemia. This report describes the first case report of Cystobasidium minutum causing fungemia in Brazil. The pathogens fungemia was demonstrated by catheter and blood culture-proven, and both yeasts were identified by sequences of D1/D2 rDNA region. After the end of antifungal therapy and catheter removal, a second blood culture was found to be negative and the clinical signs and symptoms of the patient improved.

Topics: Amphotericin B; Antifungal Agents; Basidiomycota; Brazil; Catheter-Related Infections; Deoxycholic Acid; DNA, Fungal; DNA, Ribosomal; Drug Combinations; Female; Fungemia; Humans; Immunocompromised Host; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Neutropenia

Orbital apex syndrome as a result of invasive fungal sinusitis is a disease entity most commonly found in immunocompromised patients. Infectious invasion affecting the orbital apex can have devastating visual and life-threatening consequences.

Topics: Aged; Alternaria; Alternariosis; Amphotericin B; Combined Modality Therapy; Debridement; Eye Infections, Fungal; Follow-Up Studies; Fungemia; Humans; Immunocompromised Host; Injections, Intralesional; Male; Orbital Diseases; Risk Assessment; Sinusitis; Syndrome; Tomography, X-Ray Computed; Treatment Outcome

Topics: Amphotericin B; Anti-HIV Agents; Cesarean Section; Debridement; Dermatomycoses; Drug Therapy, Combination; Fungemia; Gestational Age; HIV Infections; Humans; Immunocompromised Host; Infant; Infant, Premature; Infant, Very Low Birth Weight; Infusions, Intravenous; Male; Necrosis; Prognosis; Risk Assessment; Treatment Outcome; Umbilical Veins; Umbilicus

Fusarium spp. are an uncommon cause of fungaemia in immunocompromised and neutropenic patients that may hematogenously disseminate to the eyes. Herein, we describe a patient with acute lymphoblastic leukaemia and a prior history of extensive corticosteroid exposure who developed disseminated Fusarium solani infection following chemotherapy despite posaconazole prophylaxis. She was successfully treated with combination liposomal amphotericin B and voriconazole, intraocular injections of voriconazole, topical amphotericin B and bilateral vitrectomy. We also review published literature describing the management of endogenous Fusarium endophthalmitis in immunocompromised hosts.

Topics: Amphotericin B; Antifungal Agents; Drug-Related Side Effects and Adverse Reactions; Endophthalmitis; Female; Fungemia; Fusariosis; Fusarium; Humans; Immunocompromised Host; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole

Non-Candida opportunistic yeasts are emerging causes of bloodstream infection (BSI) in immunocompromised hosts. However, their clinical presentation, management, and outcomes in stem cell transplant (SCT) recipients are not well described. We report the first case to our knowledge of Pseudozyma BSI in a SCT recipient. He had evidence of cutaneous involvement, which has not been previously described in the literature. He became infected while neutropenic and receiving empiric micafungin, which is notable because Pseudozyma is reported to be resistant to echinocandins. He was successfully treated with the sequential use of liposomal amphotericin B and voriconazole. A review of the literature revealed nine reported instances of Pseudozyma fungemia. We performed a retrospective review of 3557 SCT recipients at our institution from January 2000 to June 2015 and identified four additional cases of non-Candida yeast BSIs. These include two with Cryptococcus, one with Trichosporon, and one with Saccharomyces. Pseudozyma and other non-Candida yeasts are emerging pathogens that can cause severe and disseminated infections in SCT recipients and other immunocompromised hosts. Clinicians should have a high degree of suspicion for echinocandin-resistant yeasts, if patients develop breakthrough yeast BSIs while receiving echinocandin therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cryptococcus; Cytarabine; Dermatomycoses; Echinocandins; Exanthema; Fever; Fungemia; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Idarubicin; Immunocompromised Host; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lipopeptides; Male; Micafungin; Opportunistic Infections; Retrospective Studies; Saccharomyces; Salvage Therapy; Trichosporon; Ustilaginales; Vidarabine; Voriconazole; Yeasts

Fusarium species are ubiquitously present in environment and are well known as human pathogens with high mortality rate in immunocompromised patients. We report here two cases where immunocompromised patients developed fatal bloodstream infections by this organism. Isolates were further identified by ITS1 region sequencing which confirmed them as Fusarium solani. Antifungal susceptibility testing was done following CLSI M38-A2 guidelines to amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, and micafungin. Both patients had a fatal outcome and expired of septic shock. Therefore, identification up to species level is of utmost importance as that helps in directing the management of the patient thereby leading to a favourable outcome.

Topics: Adolescent; Aged; Amphotericin B; Antifungal Agents; Base Sequence; DNA, Intergenic; Fluconazole; Fungemia; Fusariosis; Fusarium; Humans; Immunocompromised Host; India; Male; Microbial Sensitivity Tests; Sequence Analysis, DNA; Shock, Septic

Histoplasmosis is a progressive disease caused by dimorphic intracellular fungi and can prove fatal. Usually, it is present in immunocompromised individuals and immunocompetent individuals in the endemic zones. We report an unusual presentation of progressive disseminated histoplasmosis. The patient in the present case report was immunocompetent child and had fever, bone pains, gradual weight loss, lymphadenopathy and hepatosplenomegaly. Disseminated histoplasmosis (DH) was diagnosed on microscopic examination and fungal culture of bone marrow, blood, skin biopsy and lymph node aspirate. The patient died on seventh day of amphotericin B. In the absence of predisposing factors and classical clinical presentation of febrile neutropenia, lung, adrenal and oropharyngeal lesions, the disease posed a diagnostic challenge. Progressive disseminated histoplasmosis in children can be fatal despite timely diagnosis and therapy. In India, disseminated histoplasmosis is seen in immunocompetent hosts. All the pediatrics immunocompetent cases from India are also reviewed.

Topics: Amphotericin B; Antifungal Agents; Child; Fatal Outcome; Female; Fungemia; Histoplasma; Histoplasmosis; Humans; India

Cryptococcus neoformans infection usually presents as chronic meningitis and is increasingly being recognized in immunocompromised patients. Presentation with pleural effusion is rare in cryptococcal disease; in fact, only 4 cases of pleural effusion as the initial clinical presentation in cryptococcosis have been reported in English-language literature to date. We report the first case of pleural effusion as the initial clinical presentation in a renal transplant recipient who was initially misdiagnosed with tuberculous pleuritis but who then developed fungaemia and disseminated cryptococcosis. The examination of this rare manifestation and the accompanying literature review will contribute to increased recognition of the disease and a reduction in misdiagnoses.. We describe a 63-year-old male renal transplant recipient on an immunosuppressive regimen who was admitted for left pleural effusion and fever. Cytological examinations and pleural fluid culture were nonspecific and negative. Thoracoscopy only found chronic, nonspecific inflammation with fibrosis in the pleura. After empirical anti-tuberculous therapy, the patient developed an elevated temperature, a severe headache and vomiting and fainted in the ward. Cryptococci were specifically found in the cerebrospinal fluid following lumbar puncture. Blood cultures were twice positive for C. neoformans one week later. He was transferred to the respiratory intensive care unit (RICU) immediately and was placed on non-invasive ventilation for respiratory failure for 2 days. He developed meningoencephalitis and fungaemia with C. neoformans during hospitalization. He was given amphotericin B liposome combined with 5-flucytosine and voriconazole for first 11 days, then amphotericin B liposome combined with 5-flucytosine sustained to 8 weeks, after that changed to fluconazole for maintenance. His condition improved after antifungal treatment, non-invasive ventilation and other support. Further pathological consultation and periodic acid-Schiff staining revealed Cryptococcus organisms in pleural sections, providing reliable evidence for cryptococcal pleuritis.. Pleural effusion is an unusual manifestation of cryptococcosis. Cryptococcal infection must be considered in the case of patients on immunosuppressives, especially solid-organ transplant recipients, who present with pleural effusion, even if pleural fluid culture is negative. Close communication between the pathologist and the clinician, multiple special biopsy section stains and careful review are important and may contribute to decreasing misdiagnosis.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Flucytosine; Fungemia; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Pleural Effusion; Voriconazole

The management of neonatal sepsis is challenging owing to complex developmental and environmental factors that contribute to inter-individual variability in the pharmacokinetics and pharmacodynamics of many antimicrobial agents. In this review, we describe (i) the changing epidemiology of early- and late-onset neonatal sepsis; (ii) the pharmacologic considerations that influence the safety and efficacy of antibacterials, antifungals, and immunomodulatory adjuvants; and (iii) the recommended dosing regimens for pharmacologic agents commonly used in the treatment and prevention of neonatal sepsis. Neonatal sepsis is marked by high morbidity and mortality, such that prompt initiation of antimicrobial therapy is essential following culture collection. Before culture results are available, combination therapy with ampicillin and an aminoglycoside is recommended. When meningitis is suspected, ampicillin and cefotaxime may be considered. Following identification of the causative organism and in vitro susceptibility testing, antimicrobial therapy may be narrowed to provide targeted coverage. Therapeutic drug monitoring should be considered for neonates receiving vancomycin or aminoglycoside therapies. For neonates with invasive fungal infections, the development of new antifungal agents has significantly improved therapeutic outcomes in recent years. Liposomal amphotericin B has been found to be safe and efficacious in patients with renal impairment or toxicity caused by conventional amphotericin B. Antifungal prophylaxis with fluconazole has also been reported to dramatically reduce rates of neonatal invasive fungal infections and to improve long-term neurodevelopmental outcomes among treated children. Additionally, several large multicenter studies are currently investigating the safety and efficacy of oral lactoferrin as an immunoprophylactic agent for the prevention of neonatal sepsis.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacteremia; Bacterial Infections; Drug Monitoring; Fungemia; Humans; Infant; Infant, Newborn; Mycoses

Fungemia is a serious problem within neonatal intensive care units around the world. Premature infants are at high risk for this complication, which is often fatal. Prophylaxis for invasive fungal infection has been practiced worldwide in different settings and with various patient groups. Both oral and intravenous drugs have been used with some success. In the population of preterm infants, oral nystatin, intravenous fluconazole, and intravenous amphotericin B have all been cited as possible drugs for prophylactic use. Intravenous fluconazole has emerged as the best choice for chemoprophylaxis in premature infants.

Topics: Administration, Intravenous; Administration, Oral; Amphotericin B; Antifungal Agents; Aspergillosis; Candidemia; Fluconazole; Fungemia; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Malassezia; Nystatin; Zygomycosis

Topics: Aged; Amphotericin B; Antifungal Agents; Biopsy, Needle; Blastomycosis; Canada; Diagnosis, Differential; Fever; Follow-Up Studies; Fungemia; Humans; Immunohistochemistry; Low Back Pain; Male; Native Hawaiian or Other Pacific Islander; Rare Diseases; Skin Diseases, Vesiculobullous; Treatment Outcome

Pseudozyma spp are amorphic yeasts. They are commonly plant pathogens, but rarely cause invasive fungal disease in humans. Only three cases of central venous catheter (CVC)-associated blood stream infections due to this organism have been reported in the literature. Main underlying risk factors for Pseudozyma spp infection are bowel surgery, CVC and total parenteral nutrition. We present a rare case of Pseudozyma spp catheter-associated blood stream infection that was successfully treated with antifungal therapy and removal of CVC. It is important to recognise and differentiate this species from other yeasts as it may require the use of amphotericin B or voriconazole instead of fluconazole, to which the organism is variably resistant.

Topics: Amphotericin B; Antifungal Agents; Catheter-Related Infections; Catheterization, Central Venous; Central Venous Catheters; Female; Fluconazole; Fungemia; Humans; Middle Aged; Mycoses; Risk Factors; Voriconazole; Yeasts

Rhodotorula species have been increasingly recognized as emerging pathogens, particularly in immunocompromised patients. We herein report on a patient with myelodysplastic syndrome who developed fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor. He developed severe acute graft-versus-host disease requiring high-dose steroids, and had serially been administered fluconazole and micafungin for the prophylaxis of fungal infection. Although several cases of Rhodotorula infection after HSCT have been reported, all of them were recipients of autologous HSCT, not allogeneic HSCT. A review of all the reported cases of Rhodotorula infection after HSCT revealed that all patients had received fluconazole or echinocandins before the onset of infection. The findings suggest that Rhodotorula species could be causative yeasts, particularly in patients receiving fluconazole or echinocandins, both of which are inactive against the species.

Topics: Amphotericin B; Antifungal Agents; Fungemia; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Mycoses; Myelodysplastic Syndromes; Rhodotorula; Transplantation, Homologous; Unrelated Donors

Topics: Amphotericin B; Antifungal Agents; Back Pain; Coccidioidomycosis; Diagnosis, Differential; Female; Follow-Up Studies; Fungemia; Humans; Itraconazole; Magnetic Resonance Imaging; Middle Aged; Osteomyelitis; Physical Examination; Severity of Illness Index; Spinal Diseases; Thoracic Vertebrae; Treatment Outcome

The frequency of invasive fungal infections, and specifically invasive aspergillosis, has increased in the last few decades. Despite the development of new antifungal agents, these infections are associated with high mortality, ranging from 40% to 80%, depending on the patient and the localization of the infection. To reduce these figures, several therapeutic strategies have been proposed, including combination therapy. Most of the available data on the efficacy of these combinations are from experimental models, in vitro data and retrospective observational studies or studies with a small number of patients that have included both patients in first-line treatment and those receiving rescue therapy; in addition there are many patients with possible forms of aspergillosis and few with demonstrated or probable forms. To date, there is no evidence that combination therapy has significantly higher efficacy than monotherapy; however, combination therapy could be indicated in severe forms of aspergillosis, or forms with central nervous involvement or extensive pulmonary involvement with respiratory insufficiency, etc. Among the combinations, the association of an echinocandin--the group that includes micafungin--with voriconazole or liposomal amphotericin B seems to show synergy. These combinations are those most extensively studied in clinical trials and therefore, although the grade of evidence is low, are recommended by the various scientific societies.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Caspofungin; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Echinocandins; Forecasting; Fungemia; Guinea Pigs; Humans; Invasive Pulmonary Aspergillosis; Lipopeptides; Meningitis, Fungal; Micafungin; Mice; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Retrospective Studies; Triazoles

Kodamaea (Pichia) ohmeri is a yeast-like fungus that has recently emerged as an important etiologic agent of fungemia in immunocompromised patients. We report such a case in a premature neonate born at 29 weeks of gestation. Prior to developing fungemia, she had two episodes of bacterial sepsis on day 13 and day 32 due to Enterobacter cloacae and Staphylococcus epidermidis, respectively. Kodamaea ohmeri was repeatedly isolated from blood cultures and its identity was determined by phenotypic characteristics and sequencing of the ITS and D1/D2 regions of rDNA. The neonate was successfully treated with amphotericin B. The published cases of K. ohmeri fungemia reported in pediatric patients are reviewed highlighting its increasing importance as a bloodstream pathogen.

Topics: Amphotericin B; Antifungal Agents; Bacteremia; Communicable Diseases, Emerging; DNA, Fungal; DNA, Ribosomal; DNA, Ribosomal Spacer; Enterobacter cloacae; Female; Fungemia; Humans; Infant, Newborn; Microbial Sensitivity Tests; Molecular Sequence Data; Mycological Typing Techniques; Phylogeny; Saccharomycetales; Sequence Analysis, DNA; Staphylococcus epidermidis; Treatment Outcome

Rhodotorula is emerging as an important cause of nosocomial and opportunistic infections. We present two cases of Rhodotorula mucilaginosa fungemia diagnosed over a period of 3 months at our hospital. The first case was of a pre-term neonate in the neonatal ICU who presented with respiratory failure and sepsis. The second involved an adult female who had been injured in a road traffic accident requiring an operation for a hematoma and was later shifted to the medical ICU. For a new hospital like ours, finding two cases of Rhodotorula fungemia within a span of 3 months prompted us to describe them in this report. These cases emphasize the emerging importance of Rhodotorula mucilaginosa as a pathogen and the importance of identification and MIC testing for all fungal isolates recovered from the blood stream.

Topics: Amphotericin B; Antifungal Agents; Catheterization, Central Venous; Female; Fungemia; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Microbial Sensitivity Tests; Middle Aged; Opportunistic Infections; Pyrimidines; Rhodotorula; Treatment Outcome; Triazoles; Voriconazole; Wounds and Injuries

When functioning properly, the immune system recognizes inhaled fungi and controls their growth, while avoiding injurious inflammation and allergy. 'Aspergillosis' represents a spectrum of clinical diseases resulting from impaired or excessive immune responses. Invasive aspergillosis is principally disease of severely immunocompromised patients, whereas allergic forms of aspergillosis result from an excessive inflammatory response to hyphae colonizing the sinopulmonary tract. We will review insights gained in host defense against Aspergillus species and the immunopathogenesis of Aspergillus-related diseases as well as important advances made in fungal diagnostics and antifungal therapy.. Important advances have been made in diagnosis of invasive aspergillosis and in antifungal agents. Voriconazole was superior to amphotericin B deoxycholate as primary therapy for invasive aspergillosis. There is significant interest in combination antifungal therapy for invasive aspergillosis. Fungal genomics offers a powerful opportunity to gain knowledge about fungal virulence factors that can be targets for drug development. In addition, new insights have been gained regarding host defense against Aspergillus species that may be exploited therapeutically.. We have gained substantial knowledge regarding how the immune system recognizes inhaled fungi and calibrates the inflammatory response. There has also been substantial progress in tools to diagnose aspergillosis and in antifungal therapeutics. Future progress will likely involve the development of more refined diagnostic tools, new classes of antifungal agents, and greater knowledge of pathogen and host factors that predispose to aspergillosis.

Topics: Amphotericin B; Antifungal Agents; Antigens, Fungal; Aspergillus; DNA, Fungal; Female; Fungemia; Humans; Immunocompromised Host; Incidence; Male; Prognosis; Pulmonary Aspergillosis; Pyrimidines; Risk Assessment; Severity of Illness Index; Survival Rate; Triazoles; Voriconazole

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 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

Combined, simultaneous or sequential antifungal therapy has often been considered an appropriate option to improve the results obtained with monotherapy. Anidulafungin belongs to the echinocandin family, which has a different mechanism of action from the remaining antifungal agents, a characteristic that heralds a good chance of synergy with other groups. However, most of the data available on the efficacy of different combinations comes from animal models of infection, "in vitro" data and case reports, while data from controlled clinical trials are scarce. The available data are insufficient to allow us to conclude that the efficacy of combined therapy is significantly superior to that of monotherapy. However, the efficacy of combined therapy may be adequate for the treatment of severe invasive mycoses associated with high mortality rates, such as forms of aspergillosis that provoke central nervous system involvement, extensive pulmonary involvement, cavitated areas, or respiratory failure and infections caused by multiresistant fungi.

Topics: Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Azoles; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Echinocandins; Encephalomyelitis; Fungemia; Guinea Pigs; Humans; Lung Diseases, Fungal; Mice; Mycoses

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

Rhodotorula spp. are emergent opportunistic pathogens, particularly in immunocompromised individuals. They have been associated with endocarditis, peritonitis, meningitis endophthalmitis and catheter-associated fungemia. The aim of this study was to review all cases of central venous catheter-related fungemia due to Rhodotorula spp. reported in the literature in order to determine the best management of this uncommon infection. All patients but one in the 88 cases examined had some form of underlying disease including sixty-nine (78.4%) who had cancer. Rhodotorula mucilaginosa was the species most frequently recovered (75%), followed by Rhodotorula glutinis (6%). Amphotericin B deoxycholate was the most common antifungal agent used as treatment and the overall mortality was 9.1% in this review. This fungemia is a rare disease which can be found in immunocompromised and in the intensive care patients. The use of specific antifungal therapy may be associated with an increase in the survival. It should be noted that Rhodotorula spp. is resistant to fluconazole.

Topics: Amphotericin B; Antifungal Agents; Catheterization, Central Venous; Catheters, Indwelling; Deoxycholic Acid; Drug Combinations; Female; Fungemia; Humans; Male; Rhodotorula

The complexity of invasive Aspergillosis management, which needs many interventions, is the cause of important controversies. Resistance to azoles is increasingly common due to the selective pressure from antifungals. The response rates to caspofungin of 40% to 56% have been observed in invasive aspergillosis treatment, indicating that it is comparable to other first-line options. Combination therapy is often used in clinical practice for invasive aspergillosis treatment. But for the choice of therapy, an individual approach to patient management that considers immunosuppression, comorbidities, and site of infection, is necessary. Currently, early diagnosis, judicious use of azoles, caspofungin, and lipid amphotericin B alone or in combination, and immune restoration are keys for treatment success.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Caspofungin; Disease Management; Drug Resistance, Multiple, Fungal; Drug Therapy, Combination; Echinocandins; Fungemia; Humans; Immunocompromised Host; Lipopeptides; Treatment Outcome; Triazoles

Febrile neutropenic patients who receive antibiotics are at risk for fungal infections. This risk increases greatly with the length and severity of neutropenia. Because diagnostic tests for fungal infections lack sensitivity and specificity and because established fungal infections are associated with poor outcomes, empiric antifungal therapy is frequently given to patients with fever that persists despite antibacterial therapy. Early trials of empiric amphotericin B showed reductions in the number of invasive fungal infections and in related morbidity and mortality. However, as a result of infusion-related and renal adverse effects of amphotericin B, newer agents, such as lipid formulations of amphotericin B, extended-spectrum azoles, and echinocandins, have been developed. Although these alternatives have been associated with decreased toxicity, improved efficacy has not been clearly demonstrated. Although empiric antifungal therapy can prevent undetected breakthrough infections and morbidity associated with many fungal infections, its shortcomings include overtreatment, toxicity, and increased costs of unnecessary treatment. Recent studies have highlighted several questions in trial design and data interpretation. For example, what is the appropriate study design? Who should be enrolled in studies of empiric antifungal therapy? How should successful therapy be defined? These issues are reviewed to determine whether new antifungal agents should be evaluated for empiric use in patients with fever and neutropenia.

Topics: Amphotericin B; Antifungal Agents; Azoles; Chemistry, Pharmaceutical; Echinocandins; Fever of Unknown Origin; Fungal Proteins; Fungemia; Humans; Immunocompromised Host; Neutropenia; Peptides, Cyclic; Randomized Controlled Trials as Topic; Research Design

Clinicians face an increasing occurrence of invasive fungal infections. These are due not only to traditional yeast and mould species but also to rare pathogens that can be difficult to treat. The introduction of new agents has expanded the options for treating common and rare mycotic infections with antifungal efficacy at least equal, and safety far superior, to that of a once-limited choice of therapies. Patients with invasive mycoses frequently have concomitant disorders and require multidrug regimens. Clinicians must be aware of the potential for interactions among agents available for treating invasive mycoses in patients with serious underlying conditions.

Topics: Amphotericin B; Antifungal Agents; Azoles; Drug Interactions; Echinocandins; Fungal Proteins; Fungemia; Humans; Peptides, Cyclic

Coccidioidomycosis is an uncommon fungal infection during pregnancy. We report a case and review the literature on coccidioidomycosis in pregnancy.. We searched MEDLINE (1966-2005), PubMed (1950-2005), Embase (1974-2005), the Cochrane Library, and the Index-Catalogue of the Library of the Surgeon-General's Office United States Army (1880-1961) for cases of coccidioidomycosis occurring during pregnancy. We describe a woman with disseminated coccidioidomycosis during the last trimester of pregnancy with fungemia, respiratory failure, a miliary pattern on chest radiograph, and skin and bony involvement.. We identified 80 additional cases of coccidioidomycosis occurring with pregnancy in the literature. The mean age of patients was 26 years (range 16-38 years). Disseminated disease was strongly associated with the trimester of pregnancy; 40% of the cases diagnosed before pregnancy, 50% of the cases diagnosed in the first trimester, 62% of the cases diagnosed in the second trimester, and 96% of the cases diagnosed in the third trimester had dissemination (P<.001). In addition, African American women had a 13-fold increased risk of dissemination compared with white women (P=.007).. Mortality rates have improved over time in association with the timely administration of antifungal therapy. Disseminated coccidioidomycosis may occur during pregnancy, especially during the third trimester. Improved maternal and fetal survival is associated with early disease recognition and administration of amphotericin B.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Black or African American; Coccidioides; Coccidioidomycosis; Female; Fungemia; Humans; Male; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Pregnancy Trimesters; Severity of Illness Index; Treatment Outcome; United States; White People

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Fatal Outcome; Fungemia; Humans; Infant; Lung Diseases, Fungal; Male; Mycoses

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

To evaluate the clinical characteristics of patients affected by hematologic malignancies who developed mucormycosis and to ascertain the factors which influenced the outcome following mycotic infection.. This was a retrospective study conducted over a 15-year period (1987-2001). The study included 59 patients with hematologic malignancies with a proven or probable mucormycosis admitted in 18 Hematology Divisions in tertiary care or university hospitals.. The most frequent sites of infection were lung (64%) and orbito-sinus-facial (24%); cerebral involvement observed in 19% of cases was always associated with other sites of infection. Antifungal treatment was empirically administered in 49 patients (83%); 7 patients underwent radical surgical debridement (12%). Therapy was successful for only 18 patients (37%). Forty-seven patients died within 3 months of the diagnosis of fungal infection: the cause of death was mucormycosis in 41 patients (87%) and progression of hematologic disease in 6 patients (13%). At univariate analysis, the factors that correlated with a positive outcome from infection were the following: male sex, amphotericin B treatment, neutrophil recovery from post-chemotherapy aplasia. At multivariate analysis, the only factor that significantly correlated with recovery from infection was the liposomal amphotericin B treatment.. Mucormycosis is a rare filamentous fungal infection that occurs most frequently in neutropenic patients with acute leukemia. It does not seem to have increased in recent years. Although a reduction of mortality has been observed recently, the mortality rate still remains high. Extensive and aggressive diagnostic and therapeutic procedures are essential in order to improve the prognosis in these patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Encephalitis; Female; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Italy; Lung Diseases, Fungal; Male; Middle Aged; Mucormycosis; Neutropenia; Retrospective Studies; Risk Factors; Sinusitis; Treatment Outcome; Triazoles

Topics: Amphotericin B; Antifungal Agents; Fungemia; Humans; Immunocompromised Host; Mycoses; Neoplasms; Neutropenia; Premedication; Randomized Controlled Trials as Topic; Risk Factors; Triazoles

Persistent or recurrent unexplained fever in neutropenic patients receiving antibiotics can be caused by invasive fungal infections, which are often difficult to diagnose. Early trials of empirical antifungal therapy with amphotericin B deoxycholate (AmB) documented reductions in the frequency of and the morbidity and mortality associated with invasive fungal infections. Because of AmB's infusional and renal toxicities, subsequent trials used newer, less toxic agents, such as the lipid formulations of AmB, the extended-spectrum azoles, and, more recently, the echinocandins. To date, alternatives to AmB have shown less toxicity, but improved efficacy has been less clear. Overall, empirical antifungal therapy can help prevent the morbidity associated with many fungal infections, eliminate concerns about diagnostic pitfalls, and prevent breakthrough undetected infections. However, its potential shortcomings are overtreatment, toxicity, and increased treatment-related costs when treatment is given to persons not needing it. Newer diagnostic tools are needed to target those most in need of antifungal therapy.

Topics: Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Deoxycholic Acid; Drug Combinations; Fever; Fluconazole; Fungemia; Humans; Immunocompromised Host; Neutropenia; Opportunistic Infections

Fungal infections caused by Fusarium in the immunocompromised host are highly resistant to all antifungal agents. Fusarium endocarditis is a rare and usually fatal disease. We report an immunocompromised child who survived Fusarium solani endocarditis despite the in vitro resistance of the organism to all available antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Endocarditis; Female; Follow-Up Studies; Fungemia; Fusarium; Humans; Immunocompromised Host; Infant; Leukemia, Myeloid, Acute; Liposomes; Opportunistic Infections; Pyrimidines; Risk Assessment; Treatment Outcome; Triazoles; Voriconazole

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

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

Fungal infections caused by Candida species have increased in incidence during the past two decades in England, North America and Europe. Candidal arthritis is rare in patients who are not intravenous drug users or are who not using a prostheses. We report the case of a 24-year-old man with acute lymphoid leukemia, who developed Candida tropicalis arthritis during an aplastic period after chemotherapy. This is the eighth case described in the literature of C. tropicalis causing arthritis without intra-articular inoculation. We call attention to an unusual first sign of fungal infection: septic arthritis without intra-articular inoculation. However, this case differs from the other seven, since despite therapy a fast and lethal evolution was observed. We reviewed reported cases, incidence, risk factors, mortality and treatment of neutropenic patients with fungal infections.

Topics: Adult; Amphotericin B; Antifungal Agents; Arthritis, Infectious; Candida tropicalis; Fatal Outcome; Fungemia; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma

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

Reported here are two cases of candidemia caused by Candida lusitaniae that occurred in two immunocompromised patients at Hospital Universitario "La Fe" in Valencia, Spain. Case 1 involved a low-birth-weight premature infant with congenital nephrotic syndrome who was successfully treated with amphotericin B, and case 2 involved a 50-year old woman with a high-grade malignancy lymphoma who succumbed to the infection. Antifungal susceptibility testing of the Candida lusitaniae isolates recovered from both patients revealed sensitivity to amphotericin, 5-flucytosine and fluconazole. Results are presented and discussed together with a comprehensive review of the literature, covering all previously reported cases of fungemia caused by this emerging pathogen.

Topics: Amphotericin B; Antifungal Agents; Candida; Female; Fungemia; Humans; Infant, Newborn; Middle Aged; Opportunistic Infections

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

The incidence of invasive aspergillosis is increasing parallel to the intensity of immunosuppressive and myelosuppressive anticancer treatments. Successful management is linked to an understanding of the pathogenesis and recognition of risk factors. Identifying the patients and clinical circumstances associated with the highest risk for invasive aspergillosis and managing patients in protected environments remain the most effective means of prevention. Early accurate diagnosis continues to be a challenge; however, newer non-culture-based methods are encouraging and have been incorporated into standardized case definitions. Unacceptably high mortality rates persist with current treatment of established infection. Among the newer potentially less toxic antifungal therapies are the triazoles, and lipid-based polyene-formulations that target the fungal cell membrane and 1,3-beta-D-glucan synthase inhibitors that target the fungal cell wall. These agents are currently in clinical trials. Host defense augmentation using hematopoietic growth factors with or without other cytokines such as interferon-gamma or hematopoietic growth factor-stimulated neutrophil transfusions remain controversial strategies that have yet to be tested in well-designed randomized controlled trials.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Fungemia; Humans; Immunocompromised Host; Itraconazole; Risk Factors

Trichosporon beigelii is a fungus once thought to cause only superficial infections, but recently has been increasingly identified as an opportunistic systemic pathogen in immunocompromised patients. There have been very limited reports of this organism in the burn patient population. We describe the first report of pharmacological management of invasive T. beigelii with a combination of amphotericin B and high dose fluconazole in a burn patient. Antifungal susceptibility testing of T. beigelii determined a change in minimum inhibitory concentrations (MICs) of amphotericin B and a consistent resistance pattern with the use of flucytosine. This paper will review our experience with T. beigelii fungus in a regional burn treatment center and review the literature on other experiences in the burn population.

Topics: Adult; Amphotericin B; Antifungal Agents; Burns; Catheters, Indwelling; Drug Resistance, Microbial; Fatal Outcome; Female; Fluconazole; Flucytosine; Fungemia; Humans; Immunocompromised Host; Male; Mycoses; Opportunistic Infections; Sputum; Trichosporon; Wound Infection

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

Three cases of Clavispora lusitaniae invasive fungal infections are reported. All three infections appeared in cancer patients presented with fungaemia, one additionally with meningitis. Two of them were breakthrough -- they developed during therapy with conventional amphotericin B with a dose of 0.5 mg kg(-1) day(-1) . All three were cured: two with intravenous fluconazol and one with an increasing dose (1 mg kg(-1) day(-1)) of amphotericin B. In one of two breakthrough cases the sensitivity of the strain to antifungals was tested against antifungal agents and showed in vitro resistance to amphotericin B (MIC 2 eta g ml(-1)).

Topics: Adult; Amphotericin B; Antifungal Agents; Child, Preschool; Fluconazole; Fungemia; Humans; Meningitis, Fungal; Neoplasms; Saccharomycetales

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

Three published clinical trials of the efficacy of amphotericin B colloidal dispersion (ABCD) against infections caused by Aspergillus spp were reviewed. A total of 376 patients was treated. Systemic aspergillosis was identified in 67 evaluable patients. Overall, a complete or partial response was achieved in 47.8% of the evaluable patients, although there were substantial differences in the response rates between studies. Reasons for recruitment caused a marked difference in response rates. The overall response rate for ABCD in patients in which conventional amphotericin B (CAB) was contra-indicated or had previously failed was 34.3%, whereas the response rate in bone marrow transplant (BMT) or patients with renal impairment was 57.9 and 62.5% respectively. The efficacy of ABCD at doses of 4 mg/kg/day appears to be at least as good as in studies using CAB. The levels of renal toxicity were low at a dose of 4 mg/kg/day. Dose-limiting studies indicate that dosages can be safely increased to 7.5 mg/kg/day creating opportunity for improved efficacy.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Clinical Trials as Topic; Fungemia; Humans; Treatment Outcome

During the past decades, the incidence and severity of invasive fungal infections has been increasing. These events have lead to the development of new antifungal agents, and amphotericin B no longer is the standard therapy for a variety of invasive mycoses. Fluconazole has become the drug of choice for treatment of C. albicans infections in non-neutropenic as well as neutropenic patients. For treatment of cryptococcal meningitis, amphotericin B with flucytosine, followed by fluconazole consolidation therapy is used. For therapy of invasive aspergillosis, the lipid formulations of amphotericin B may be associated with reduced toxicity and allow for larger doses, although the efficacy of each of the formulations still has to be established in randomized trials. Finally, treatment modalities aimed at improving host defense mechanisms, including adjunctive therapy with rG-CSF for disseminated candidiasis and rG-CSF-elicited granulocyte transfusions, are under way.

Topics: Amphotericin B; Antifungal Agents; Catheterization, Central Venous; Contraindications; Drug Therapy, Combination; Flucytosine; Fungemia; Granulocyte Colony-Stimulating Factor; Humans; Immunotherapy; Mycoses; Neutropenia; Triazoles

We report a case of fatal disseminated fungal infection by Scedosporium prolificans which occurred in a patient with acute leukemia during induction chemotherapy. Rapid clinical deterioration despite high-dose empirical amphotericin B highlights both the pathogenicity of this fungus in immunocompromised hosts and its resistance to standard antifungal therapy.

Topics: Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Resistance, Microbial; Fatal Outcome; Female; Fungemia; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Mycetoma; Pseudallescheria

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

Fungal arthritis in pediatric patients is rare and is most often associated with hematogenous spread to the affected joint. It is generally seen concomitant with, or shortly after, fungemia. We report a case of an immunocompetent patient in whom candidal arthritis developed 1 year after initial fungemia. The initial candidiasis was considered to be adequately treated with amphotericin B. The Candida isolates from the neonatal fungemia and subsequent arthritis were the some as identified by electrophoretic karyotype, restriction fragment length polymorphism analysis, and antifungal susceptibility testing. Pediatric candidal fungemia, arthritis, and their treatments are discussed.

Topics: Amphotericin B; Antifungal Agents; Arthritis, Infectious; Candida albicans; Female; Fungemia; Humans; Infant, Newborn; Karyotyping; Microbial Sensitivity Tests; Polymorphism, Restriction Fragment Length

We report three cases of zygomycosis (mucormycosis) occurring in three individuals infected with the human immunodeficiency virus (HIV) and review 12 other published cases. We present the only two case reports of disseminated zygomycosis in AIDS patients, and the only AIDS patient with renal zygomycosis to survive without nephrectomy, receiving intravenous (i.v.) amphotericin alone. Coinfection with zygomycosis and HIV is rare, occurs primarily in patients with low CD4+ lymphocyte counts, does not always require the usual predisposing conditions for zygomycosis, and may be the presenting opportunistic infection among HIV-infected persons. Transient episodes of neutropenia occurring within 4 months before presentation may be a risk factor for this disease. Zygomycosis may arise in multiple sites including the basal ganglia, cutaneous tissue, kidney, respiratory tract, and may be disseminated. Occurring more commonly in, but not restricted to, injection drug users, it is significantly associated with sites other than basal ganglia in those patients with advanced HIV disease or AIDS. The presenting symptoms are related to the site of involvement, and the illness may develop insidiously or progress rapidly to a fulminant course. Successful therapy usually consists of surgical debridement and intravenous amphotericin B. Overall mortality in this review is 40%, and is significantly associated with sites of disease inaccessible to surgical debridement.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; CD4 Lymphocyte Count; Female; Fungemia; Humans; Intestinal Diseases; Intestine, Small; Kidney; Kidney Diseases; Male; Middle Aged; Mucorales; Mucormycosis; Neutropenia

Topics: Acremonium; Amphotericin B; Catheterization, Central Venous; Child, Preschool; Drug Therapy, Combination; Female; Fluconazole; Fungemia; Humans; Immunocompromised Host; Male

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

We present two cases of aspergillus infection confirmed by blood culture and review 30 other cases of genuine aspergillus fungemia and 34 cases of aspergillus pseudofungemia. Multiple different media and blood culture systems were used to isolated Aspergillus. The median time to positive blood culture was 8.5 days (range, 1-27 days) in the genuine cases. Genuine aspergillus fungemia was observed more often after cardiac surgery (n = 11 [34%]) or during neutropenia (n = 9 [28%]) than in other settings. In a recent series of fungemia during neutropenia, 7.6% of all episodes were due to Aspergillus. Other patients at risk for aspergillus fungemia were similar to those at risk for invasive aspergillosis, including patients with AIDS. Seven (44%) of 19 patients who were treated survived. In the group of patients with aspergillus pseudofungemia, there were no deaths, and cultures of additional specimens from the same patient were not positive. Criteria that may be applied to ascertain whether the isolation of Aspergillus from blood cultures is clinically significant are put forward.

Topics: Aged; Amphotericin B; Aspergillosis; Eye Diseases; Eye Infections, Fungal; Female; Fungemia; Humans; Male; Middle Aged

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

To assess the role of azole therapy in the treatment and prophylaxis of cryptococcosis in HIV-seropositive individuals.. Retrospective case review.. A dedicated HIV unit in London, UK.. Fifty individuals with a positive cryptococcal antigen or culture from any site between 1 January 1985 and 31 December 1992.. Thirty-eight patients initially presented with meningitis and 12 with alternative disease, five of whom subsequently developed meningeal disease. The 12 patients who presented without meningitis received chronic suppressive therapy after the diagnosis of cryptococcal disease. Two patients receiving itraconazole developed meningitis as did three out of four treated with 200 mg fluconazole daily, but none of the six receiving 400 mg fluconazole daily. Treatment of cryptococcal meningitis was successful in 17 of the 19 patients given fluconazole but only three of the six receiving itraconazole. Following successful treatment of meningitis five out of seven patients given itraconazole and five out of seven given 200 mg fluconazole daily relapsed compared with three out of 25 receiving 400 mg fluconazole daily.. Fluconazole is an effective treatment for cryptococcal meningitis. For prophylaxis following meningitis, a dose of 400 mg fluconazole is the preferred treatment; lower doses are associated with a higher relapse rate.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Cryptococcosis; Fluconazole; Fungemia; Humans; Itraconazole; London; Meningitis, Cryptococcal; Recurrence; Retrospective Studies; Survival Analysis

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

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

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

A 6-month-old female infant, with a birth weight of 2.74 kilograms, was born with multiple congenital abnormalities, including gastric and gastrointestinal defects. She was admitted to the hospital with hematemesis. The patient could not be fed orally, and parenteral nutrition was initiated through a central venous catheter. Following pyloroplasty, she developed superior vena cava syndrome, renal disfunction and episodes of sepsis. Stool and respiratory specimens were negative for fungi, but four blood cultures yielded Hansenula anomala var. anomala. Cultures for fungi from intravenous catheter tips were negative. The baby was treated with amphotericin B (am B) and 5-fluorocytosine (5-FC), (amB; 0.1 mg/kg body weight and 5-FC, 100 mg, q.i.d.). The minimal inhibitory concentrations of am B, 5-FC, am B + 5-FC (1:1, w:w) and fluconazole to H. anomala were 1.56, less than 0.195, 1.56, and 1.56 micrograms, respectively. Following antifungal therapy and removal of the catheter, the patient tolerated oral feeding and, at the time of discharge, her weight had increased to 4.91 kg. This report records H. anomala as an opportunistic yeast pathogen for the first time in Alberta, Canada. Previously published cases of H. anomala infections are reviewed.

Topics: Abnormalities, Multiple; Amphotericin B; Ductus Arteriosus, Patent; Duodenum; Female; Fungemia; Hematemesis; Humans; Infant; Pichia

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

In patients with hematologic malignancy, invasive aspergillosis continues to be associated with high mortality even when treated with conventional antifungal therapy. To investigate novel antifungal agents, we compared 53 patients who received posaconazole salvage therapy to 52 contemporary control patients who received high-dose lipid formulation of amphotericin B (HD-LPD/AMB at > or = 7.5 mg kg(-1) per day) and 38 other control patients who received caspofungin plus HD-LPD/AMB. Patients in the three groups had similar. The overall response rate to salvage therapy was 40% for posaconazole, 8% for HD-LPD/AMB (P < or = 0.001) and 11% for combination therapy (P < 0.002). Aspergillosis contributed to the death of 40% of posaconazole group, 65% of the HD-LPD/AMB group and 68% of the combination group (P < or = 0.008). By multivariate analysis, posaconazole therapy independently improved response (9.5; 95% confidence interval, 2.8-32.5; P < 0.001). HD-LPD/AMB alone or in combination was associated with a significantly higher rate of nephrotoxicity (P < or = 0.02) and hepatotoxicity (P < 0.03). In conclusion, posaconazole salvage therapy demonstrated greater efficacy and safety than HD-LPD/AMB alone or in combination with caspofungin in the salvage therapy of invasive aspergillosis in hematologic malignancy.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Caspofungin; Combined Modality Therapy; Drug Combinations; Drug Therapy, Combination; Echinocandins; Female; Fungemia; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Itraconazole; Lipopeptides; Male; Middle Aged; Neutropenia; Phosphatidylcholines; Phosphatidylglycerols; Pyrimidines; Salvage Therapy; Treatment Outcome; Triazoles; Voriconazole

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 optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population.. Newly diagnosed patients with AML or high-risk MDS who were undergoing induction chemotherapy received prophylactic ABLC 2.5 mg/kg intravenously 3 times weekly. This treatment group was compared with a historical control group that had similar baseline characteristics and received prophylactic liposomal amphotericin B (L-AmB) 3 mg/kg 3 times weekly. The primary endpoint was the incidence of documented or suspected fungal infections during and up to 4 weeks after cessation of prophylaxis. Reported adverse events were used to assess tolerability.. The overall efficacy of antifungal prophylaxis was similar in patients who received ABLC and patients who received L-AmB (P=0.95). Among 131 ABLC-treated patients and 70 L-AmB-treated patients who were assessed for efficacy and safety, 49% of patients in each group completed therapy without developing a documented or suspected fungal infection. Documented fungal infections occurred in 5% of ABLC-treated patients and in 4% of L-AmB-treated patients. Alternative antifungal strategies were required because of persistent fever or pneumonia of unknown pathogen in 28% and 32% of ABLC-treated and L-AmB-treated patients, respectively. Grade 3 and 4 adverse events, therapy discontinuations due to adverse events, and survival rates also were similar between treatment groups.. ABLC and L-AmB appeared to have similar efficacy and were tolerated well as antifungal prophylaxis in patients with AML and high-risk MDS who were undergoing induction chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fungemia; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Liposomes; Male; Middle Aged; Myelodysplastic Syndromes; Primary Prevention; Probability; Prognosis; Remission Induction; Risk Assessment; Single-Blind Method; Survival Analysis; Treatment Outcome

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

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

Invasive aspergillosis has become the leading cause of death after allogeneic hematopoietic stem cell transplantation. This is partially due to the lack of a prompt diagnosis. Recently the detection of Aspergillus galactomannan antigen by means an ELISA technique in serum has been described. The objective of this study was to validate its usefulness in the allogeneic hematopoietic stem cell transplantation setting.

Topics: Adolescent; Adult; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Antigens, Fungal; Aspergillosis; Aspergillus; Biomarkers; Enzyme-Linked Immunosorbent Assay; False Negative Reactions; Female; Fungemia; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Male; Mannans; Middle Aged; Predictive Value of Tests; Prospective Studies; Transplantation Conditioning; 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

Animal studies have shown that fungal burden correlates with survival during treatment with new antifungal therapies for histoplasmosis. The purpose of this report is to compare the clearance of fungal burden in patients with histoplasmosis treated with liposomal amphotericin B versus itraconazole. In two separate closed clinical trials that evaluated the efficacy of liposomal amphotericin B and itraconazole treatment of disseminated histoplasmosis in patients with AIDS, blood was cultured for fungus and blood and urine were tested for Histoplasma antigen. The clinical response rates were similar; 86% with liposomal amphotericin B (n = 51) versus 85% with itraconazole (n = 59). Of the patients with positive blood cultures at enrollment, after 2 weeks of therapy cultures were negative in over 85% of the liposomal amphotericin B group versus 53% of the itraconazole group (P = 0.0008). Furthermore, after 2 weeks, median antigen levels in serum fell by 1.6 U in the liposomal amphotericin B group versus 0.1 U in the itraconazole group (P = 0.02), and those in urine fell by 2.1 U in the liposomal amphotericin B group and 0.2 U in the itraconazole group (P = 0.0005). The more rapid clearance of fungemia supports the use of liposomal amphotericin B rather than itraconazole for initial treatment of moderately severe or severe histoplasmosis.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Fungemia; Histoplasma; Histoplasmosis; Humans; Itraconazole; Liposomes; Treatment Outcome

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

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 tolerance of aerosolised amphotericin B as prophylaxis against invasive pulmonary aspergillosis was investigated in 61 granulocytopenic periods in 42 patients treated for a haematologic malignancy. Each patient was to receive amphotericin B in doses escalating to 10 mg three times daily (t.i.d.), but only 20 (48%) patients managed to complete the scheduled regimen. One patient tolerated the full dose initially, but had to discontinue treatment when dyspnea developed as a result of pneumonia and acute respiratory distress. Another 22 patients (52%) experienced side effects, including eight (19%) who reported mild coughing and dyspnea but who tolerated the full dose and three (7%) patients whose dose was reduced to 5 mg t.i.d. Another six (14%) patients could tolerate only 5 mg t.i.d., and five (12%) others stopped treatment because of intolerance. Elderly patients (p < 0.05) and those with a history of chronic pulmonary obstructive disease (p = 0.09) were more likely to develop side effects during inhalation. Twelve (28%) patients developed proven of possible invasive fungal infections, but no correlation was established between infection and the total amount of amphotericin B inhaled. Inhalation of aerosolised amphotericin B is poorly tolerated and does not appear useful in preventing invasive pulmonary aspergillosis in granulocytopenic patients.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Agranulocytosis; Amphotericin B; Antifungal Agents; Aspergillosis; Chi-Square Distribution; Confidence Intervals; Dose-Response Relationship, Drug; Female; Fungemia; Hematologic Neoplasms; Humans; Lung Diseases, Fungal; Male; Middle Aged; Treatment Outcome

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 septicemia is a devastating disease in the neonate, especially in the low birth weight preterm infant who is especially vulnerable to disseminated fungal sepsis. The objective of this study was to compare the efficacy, safety and overall convenience of fluconazole vs. amphotericin B for the treatment of disseminated fungal sepsis in neonates.. A prospective, randomized, collaborative study conducted at two South African neonatal units.. Twenty-four infants with proven fungal septicemia were treated from June, 1992, to June, 1993. Twelve received fluconazole, 11 received amphotericin B and 1 was excluded. Assessment of hepatic, renal and hematologic functions were performed before, during and after treatment. The two groups were comparable at the time of enrollment into the study.. Infants receiving amphotericin B had significantly higher values of total and direct bilirubin and alkaline phosphatase values at the end of treatment, while the fluconazole group showed a significant increase in the platelet count. The cumulative total numbers of days receiving intravenous therapy for the administration of antifungal drugs were 57 for the fluconazole group and 162 for the amphotericin group; no central lines were needed in the fluconazole group, whereas 3 babies given amphotericin B had central catheters for a cumulative total of 27 days. The case fatality rate was 33% in the fluconazole group and 45% in the amphotericin B group; there was still proof of fungal septicemia at the time of death in 1 patient given amphotericin B and 2 given fluconazole.. Fluconazole showed fewer side effects than amphotericin B and was more convenient to use.

Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Developing Countries; Drug Administration Schedule; Female; Fluconazole; Fungemia; Humans; Infant, Newborn; Injections, Intravenous; Intensive Care Units, Neonatal; Male; Prospective Studies; South Africa; Survival Rate; 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

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 results are presented of two preliminary studies conducted to assess the role of GM-CSF as adjuvant treatment in neutropenic patients with bacterial or fungal infections. In the first study the effect of GM-CSF on the rate of response to antibiotics was assessed. Febrile neutropenic patients (n = 91) were randomized to receive ticarcillin-clavulanate plus netilmicin with or without GM-CSF (60 micrograms/m2). Response rates were significantly higher in patients who received antibiotics plus GM-CSF (p = 0.05). An increase in neutrophil count was seen in 89% of GM-CSF patients with initial low neutrophil counts (< 100/microliters) compared with 67% of control patients (p = 0.04). In the second study the activity of GM-CSF in patients with fungal infections was assessed. Neutropenic patients with documented fungal infections received amphotericin B plus GM-CSF. Of the eight evaluable patients, six responded and four had a complete response to treatment. The neutrophil counts of the two non-responding patients did not increase substantially during GM-CSF treatment and both died of their fungal infection. The prognosis of neutropenic patients with fungal infections is usually poor and the results of this pilot study are therefore very encouraging. The two studies show that GM-CSF is able to stimulate neutrophil recovery in neutropenic patients and may improve the response to antibiotic and antifungal treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Female; Fungemia; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Middle Aged; Neutropenia; Prospective Studies; Treatment Outcome

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

The value of monitoring titers of cryptococcal antigen in serum and cerebrospinal fluid (CSF) during therapy for AIDS-associated cryptococcal meningitis was evaluated. Baseline and final titers of antigen in serum and CSF from participants in two studies of such therapy were categorized as increased (a rise of at least two dilutions), unchanged, or decreased (a fall of at least two dilutions). There was no correlation between outcome and changes in serum titers of cryptococcal antigen during treatment for acute meningitis or during suppressive therapy. During therapy for acute infection, an unchanged or increased titer of antigen in CSF was correlated with clinical and microbiological failure to respond to treatment; the correlation was especially strong among patients whose baseline titer of antigen was > or = 1:8 (P = .01). A rise in CSF antigen titer during suppressive therapy was associated with relapse of cryptococcal meningitis (P < .001). We conclude that serial monitoring of cryptococcal antigen, as conducted in these studies, has a limited role in the management of AIDS patients with cryptococcal meningitis.

Topics: Acute Disease; AIDS-Related Opportunistic Infections; Amphotericin B; Antigens, Fungal; Biomarkers; Cryptococcus neoformans; Fluconazole; Fungemia; Humans; Meningitis, Cryptococcal; Polysaccharides; Prognosis; Treatment Outcome

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

Saccharomyces cerevisiae is ubiquitous in the gastrointestinal tract and known as brewer's or baker's yeast. We experienced a case of S. cerevisiae and Candida glabrata co-infectious bloodstream infection. It is rare to detect both S. cerevisiae and Candida species in blood cultures together.. We treated a 73-year-old man who developed a pancreaticoduodenal fistula infection after pancreaticoduodenectomy. The patient had a fever on postoperative day 59. We took blood cultures and detected C. glabrata. Thus, we started micafungin. On postoperative day 62, we retested blood cultures, and detected S cerevisiae and C. glabrata. We changed micafungin to liposomal amphotericin B. Blood cultures became negative on postoperative day 68. We changed liposomal amphotericin B to fosfluconazole and micafungin because of hypokalemia. He got well, and we terminated antifungal drugs 18 days after the blood cultures became negative.. Co-infection with S. cerevisiae and Candida species is rare. In addition, in this case, S. cerevisiae developed from blood cultures during micafungin administration. Thus, micafungin may not be effective enough to treat S. cerevisiae fungemia, although echinocandin is considered one of the alternative therapy for Saccharomyces infections.

Topics: Aged; Antifungal Agents; Candida; Candida glabrata; Coinfection; Drug Resistance, Fungal; Echinocandins; Fungemia; Humans; Male; Micafungin; Microbial Sensitivity Tests; Saccharomyces cerevisiae

Topics: Amphotericin B; Antifungal Agents; Basidiomycota; Blast Crisis; Caspofungin; Cerebrospinal Fluid; Child; Drug Therapy, Combination; Eye Infections, Fungal; Fatal Outcome; Female; Fungemia; Humans; Leukemia, Myeloid, Acute; Retinitis; Trichosporonosis; Voriconazole

Invasive trichosporonosis is a rare and lethal fungal infection that occurs in immunocompromised patients. Breakthrough trichosporonosis can occur in patients treated with echinocandins since Trichosporon spp. are resistant to these antifungal agents. We report a case of breakthrough Trichosporon asahii fungemia. A 62-year-old Japanese woman with relapsed follicular lymphoma was treated empirically with broad-spectrum antibiotics and micafungin due to an intermittent fever during reinduction chemotherapy. After four cycles of anti-cancer chemotherapy, she experienced a high neutropenic fever and T. asahii was subsequently detected from a blood culture. The patient was not given voriconazole due to the contraindication for use with carbamazepine, and she was successfully treated with fluconazole plus liposomal amphotericin B without any serious complications. The combined therapy of fluconazole and liposomal amphotericin B may therefore be useful in treating T. asahii fungemia, especially in patients receiving antiepileptic agents.

Topics: Amphotericin B; Antifungal Agents; Basidiomycota; Fluconazole; Fungemia; Humans; Lymphoma, Follicular; Middle Aged; Trichosporon; Trichosporonosis

Papiliotrema laurentii (formerly Cryptococcus laurentii) and Papiliotrema albidus (formerly Cryptococcus albidus) are yeast-like environmental fungi which are largely considered as non-pathogenic to humans. However, invasive infections caused by P. laurentii have recently been reported in some patients with an impaired immune system. Here, we describe the first case of P. laurentii fungemia in a premature, very low-birth-weight neonate in Kuwait and the Middle East. Repeated bloodstream isolates were obtained and were tentatively identified as P. laurentii by Vitek 2 yeast identification system. The identification of the yeast isolates as P. laurentii was confirmed by PCR-sequencing of ribosomal DNA (rDNA). Antifungal susceptibility testing data showed that the isolates were susceptible to amphotericin B, fluconazole and voriconazole but appeared resistant to caspofungin. The baby was successfully treated with liposomal amphotericin B.

Topics: Adult; Amphotericin B; Antifungal Agents; Basidiomycota; DNA, Ribosomal; Female; Fungemia; Humans; Infant, Low Birth Weight; Infant, Newborn; Kuwait; Male; Mycological Typing Techniques; Treatment Outcome

We report on a 22-years-old Thai male patient with congenital HIV infection. Due to his non-adherence to antiretroviral treatment he developed disseminated

Topics: Amphotericin B; Anterior Chamber; Antifungal Agents; Fungemia; Granuloma; HIV Infections; Humans; Male; Mycoses; Talaromyces; Uveitis, Anterior; Young Adult

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Fungemia; Humans; Liver Transplantation; Patient Safety; Retrospective Studies

Cryptococcal meningitis is a fungal infection that is most commonly thought of as an opportunistic infection affecting immunocompromised patients, classically patients with Human Immunodeficiency (HIV) infection. It is associated with a variety of complications including disseminated disease as well as neurologic complications including intracranial hypertension, cerebral infarcts, vision loss and other neurologic deficits. It is diagnosed by lumbar puncture with CSF studies, including fungal culture and cryptococcal antigen testing. We present a case of cryptococcal meningitis and fungemia in a previously healthy male patient who presented after multiple emergency department visits with persistent headache. After multiple visits, he underwent a lumbar puncture consistent with cryptococcal infection, and he was admitted to the hospital for initiation of antifungal therapy. His workup revealed no known underlying condition leading to immune compromise.

Topics: Adult; Amphotericin B; Antifungal Agents; Culture Techniques; Delayed Diagnosis; Fluconazole; Flucytosine; Fungemia; Headache; Humans; Immune Reconstitution Inflammatory Syndrome; Immunocompetence; Intensive Care Units; Intracranial Hypertension; Male; Meningitis, Cryptococcal; Papilledema; Respiratory Insufficiency; Spinal Puncture; Ventriculoperitoneal Shunt

Trichosporon asahii is a yeast-like fungus that is emerging as an important cause of invasive infections in tertiary medical centres. A 58-year-old Chinese man with no known medical illnesses presented with liver lacerations and multiple fractures following an alleged 12-foot fall at a construction site. The gravity of his injuries and poor haemodynamic status necessitated an intensive care unit (ICU) admission, during which several febrile episodes were detected and multiple antibiotics were administered. After being in the ICU for at least two weeks, a urease-positive yeast was isolated from the patient's blood. The yeast formed dry, fuzzy and wrinkled white colonies on Sabouraud dextrose agar following prolonged incubation, and produced blastoconidia, true hyphae, pseudohyphae and arthroconidia on slide culture. It was identified biochemically by the ID 32 C kit as T. asahii. The yeast had elevated minimal inhibitory concentration (MIC) values to fluconazole, amphotericin B, flucytosine and all echinocandins tested. In view of this, the patient was treated with voriconazole and was successfully transferred to the general medical ward.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Basidiomycota; Drug Resistance, Multiple, Fungal; Fungemia; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multiple Trauma; Trichosporonosis; Voriconazole

Fusarium spp. may cause invasive disseminated infections in immunocompromised patients, associated with significant morbidity and mortality. We describe a case of disseminated fusariosis with fungemia and skin localization caused by Fusarium musae in a patient with acute myeloid leukemia successfully treated using liposomal amphotericin B and voriconazole.

Topics: Amphotericin B; Antifungal Agents; Fungemia; Fusariosis; Fusarium; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Voriconazole

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Biopsy; Fatal Outcome; Female; Fungemia; Humans; Immunocompromised Host; Itraconazole; Leukemia, Myeloid, Acute; Middle Aged; Skin; Treatment Failure; Trichosporon; Trichosporonosis

Opportunistic infections, while well studied in the AIDS population, continue to have variable and surprising presentations. Here, we present a case of disseminated histoplasmosis with disseminated nontuberculous mycobacterial infection in a 50 year old man with long standing AIDS living in a non-endemic area.. Patient presented with a constellation of symptoms, and imaging of the chest showed a pulmonary mass with cavitation, multiple nodules, and ground glass opacities. Further investigations revealed granulomatous lung nodules and fungemia consistent with Histoplasma capsulatum, and coinfection with disseminated nontuberculous mycobateria in a nonendemic area.. Immunocompromised patients risk co-inhabitation by multiple infectious organisms. Some of these organisms may preside in the host for years prior to reactivation. Clinicians in non endemic areas should therefore be careful to not overlook specific organisms based on a lack of a recent travel history. Physicians in nonendemic areas should become more familiar with the clinical findings and diagnostic approach of infectious such as Histoplasmosis, to ensure earlier recognition and treatment in immunocompromised individuals.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Bacterial Agents; Anti-HIV Agents; Antifungal Agents; Antitubercular Agents; Azithromycin; Bacteremia; California; Emtricitabine; Ethambutol; Fungemia; Heterocyclic Compounds, 3-Ring; Histoplasmosis; Humans; Lung; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Oxazines; Piperazines; Pyridones; Rifabutin; Tenofovir; Tomography, X-Ray Computed

The introduction of the prophylactic use of antifungal drugs caused the increased occurrence of invasive fungal infections due to previously rare molds, such as fusariosis, after allogeneic hematopoietic stem cell transplantation. We herein report the case of a patient with diffuse large B-cell lymphoma who developed fungemia due to Fusarium solani during liposormal amphotericin B on day 25 after cord blood transplantation (CBT). Because Fusarium species might differ in virulence and drug susceptibility, the sequencing of the internal transcribed spacer region of the ribosomal RNA gene accurately identified Fusarium solani to be the cause of fungemia at the species level. This case highlights Fusarium solani as the cause of fungemia in a patient under liposormal amphotericin B treatment after CBT.

Topics: Aged; Amphotericin B; Antifungal Agents; Cord Blood Stem Cell Transplantation; Fungemia; Fusarium; Humans; Male

Rhodotorula species have traditionally been considered as one of common non-virulent environmental inhabitant. They have emerged as an opportunistic pathogen, particularly in immunocompromised hosts and most infections have been associated with intravenous catheters in these patients. We review the isolates in blood cultures of Rhodotorula mucilaginosa in our Hospital. We describe the demographic and clinical features of the cases and the antifungal susceptibility profiles of the isolates. Selected patients had an isolation of R. mucilaginosa in blood cultures in our tertiary care Hospital. All data were collected retrospectively from clinical records during 5 years. We report 8 isolates in blood, two of them were considered contaminants. Immunosuppression, surgery, previous antibiotic therapy were common clinical features. For all the isolates, minimum inhibitory concentration (MIC) values were high for echinocandins and azoles and low for amphotericin B and 5-flucytosine. One strain showed atypical susceptibility profile. Rhodotorula mucilaginosa may be present on the skin and blood cultures can be contaminated. Fungaemia due to R. mucilaginosa is a rare clinical entity which requires risk factors but clinically relevant because of the multiresistant profile. Rhodotorula mucilaginosa shows high MIC values for azoles and echinocandins, therefore amphotericin B and flucytosine must be administered as antifungal therapy.

Topics: Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Azoles; Blood Culture; Child, Preschool; Echinocandins; Female; Flucytosine; Fungemia; Humans; Immunocompromised Host; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Rhodotorula; Spain; Tertiary Care Centers

New data from the years 2012 to 2015 from the Danish National Fungemia Surveillance are reported, and epidemiological trends are investigated in a 12-year perspective (2004 to 2015). During 2012 to 2015, 1,900 of 1,939 (98%) fungal bloodstream isolates were included. The average incidence was 8.4/100,000 inhabitants, and this appears to represent a stabilizing trend after the increase to 10.1/100,000 in 2011. The incidence was higher in males than females (10.0 versus 6.8) and in patients above 50 years, and those changes were mainly driven by an increasing incidence among 80-to-89-year-old males (65.3/100,000 in 2014 to 2015). The proportion of

Topics: Age Factors; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Denmark; Drug Resistance, Multiple, Fungal; Echinocandins; Epidemiological Monitoring; Female; Fluconazole; Fungemia; Humans; Incidence; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Sex Factors

We report here the isolation of Mucor velutinosus from multiple blood cultures performed on samples from Broviac catheters and culture of a Broviac insertion-site wound sample from a 6-year-old boy with a history of intestinal failure secondary to chronic intestinal pseudo-obstruction, parenteral nutrition, and jejunostomy tube dependence. Examination of a slide from the culture revealed the presence of wide nonseptate hyphae with sporangiophores, columella, and chlamydospores. The fungal isolate was sent to the National Institutes of Health for further evaluation and was identified as Mucor velutinosus by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry and genomic sequencing. The patient was treated successfully with intravenous amphotericin B and prompt removal of his central line. To the best of our knowledge, this is the first case of M velutinosus bloodstream infection in a child without cancer.

Topics: Amphotericin B; Antifungal Agents; Catheter-Related Infections; Central Venous Catheters; Child; Fungemia; Humans; Immunocompetence; Intestinal Pseudo-Obstruction; Jejunostomy; Male; Mucor; Mucormycosis; Parenteral Nutrition

Topics: Acquired Immunodeficiency Syndrome; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Retroviral Agents; Bone Marrow; Fungemia; Histoplasma; Histoplasmosis; HIV; Humans; Itraconazole; Male; Viral Load

Invasive candidiasis differs greatly between children and neonates. We aimed to investigate the different therapeutic approaches and their effects on treatment outcomes of these two groups.. Episodes of neonatal invasive candidiasis were compared with non-neonatal pediatric episodes during a 12-year cohort study. Clinical isolates were documented by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and DNA sequencing, and antifungal susceptibility testing was performed.. A total of 342 episodes of invasive candidiasis (113 neonatal and 229 non-neonatal pediatric episodes) in 281 pediatric patients (96 neonates and 185 children) were identified. Candida albicans was the most common pathogen causing invasive candidiasis in neonates and children (47.8% vs. 44.1%). The antifungal susceptibility profiles were not significantly different between neonates and children. More neonates received amphotericin B as therapy, whereas more children received fluconazole or caspofungin. Compared with children, neonates had a significantly longer duration of fungemia, higher rates of septic shock (34.5% vs. 21.8%; P = 0.013), sepsis-attributable mortality (28.3% vs. 17.5%; P = 0.024) and in-hospital mortality (42.7% vs. 25.4%; P = 0.004) than children. Independent risk factors for treatment failure of invasive candidiasis were septic shock (odds ration [OR] 16.01; 95% confidence interval [CI] 7.64-33.56; P <  0.001), delayed removal of intravenous catheter (OR 6.78; 95% CI 2.80-17.41; P <  0.001), renal failure (OR 5.38; 95% CI 1.99-14.57; P = 0.001), and breakthrough invasive candidiasis (OR 2.99; 95% CI 1.04-8.67; P = 0.043).. Neonatal invasive candidiasis has worse outcomes than non-neonatal pediatric candidiasis. Neonatologists and pediatricians must consider age-specific differences when developing treatment and prevention guidelines, or when interpreting studies of other age groups.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis, Invasive; Caspofungin; Child; Child, Preschool; Cohort Studies; Female; Fluconazole; Fungemia; Hospital Mortality; Humans; Incidence; Infant; Infant, Newborn; Male; Risk Factors; Taiwan; Treatment Outcome

Paecilomyces sp. are emerging pathogens in immunocompromised patients. We report here a case of Paecilomyces variotii fungemia, cured with amphotericin and anidulafungin, illustrating difficulties of early diagnosis and therapeutic choice in such rare fungal infection.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Echinocandins; Fungemia; Hepatic Insufficiency; Humans; Liver Transplantation; Lymphoma; Male; Middle Aged; Paecilomyces

Topics: Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Fluconazole; Fungemia; Humans; Male; Middle Aged; Schizophyllum

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Echinocandins; Female; Fluconazole; Fungemia; Geotrichosis; Geotrichum; Humans; Immunocompromised Host; Invasive Fungal Infections; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Registries; Saccharomycetales; Voriconazole; Young Adult

We report an atypical case of Rhodotorula mucilaginosa fungemia coexisting with pleural tuberculosis, in an immunocompetent host. The patient was an inhaled drug abuser and worked in a fruit market. The diagnosis of Rhodotorula mucilaginosa infection was established by the isolation of the yeast in two blood cultures followed by a good response to amphotericin B treatment. Persistent evening fever and pleural effusion led to the second diagnosis-pleural tuberculosis. In the last 5 years, this was the only case of Rhodotorula mucilaginosa fungemia in our hospital and the first case in the literature that documents Rhodotorula mucilaginosa fungemia associated with pleural tuberculosis.

Topics: Adult; Amphotericin B; Antifungal Agents; Blood; Fungemia; Humans; Male; Rhodotorula; Treatment Outcome; Tuberculosis, Pleural

Antifungal prophylaxis may be required in high-risk patients undergoing liver transplantation and for that reason we aimed to verify its role and its related impact on the graft. From January 2006 throughout 2012, 250 liver transplants were evaluated and 54 patients identified as being at higher risk were randomly selected to undergo the following schedule: 28 patients received liposomal amphotericin B and 26 received caspofungin. We evaluated, throughout 12 months, renal and liver function tests, bacterial and fungal infection episodes, and intensive care unit (ICU) stay, as well as the Th1 and Th2 cytokine network. Differences were analyzed according to non-parametric tests (two-tailed p values). Neither of the groups showed episodes of invasive fungal infection during the 12 months follow-up; however, patients receiving prophylaxis with liposomal amphotericin B had reduced episodes of bacterial infections coupled with an improved immune system response compared with those receiving caspofungin. Finally, a reduced stay in the ICU was also observed. In conclusion, even if the results of liposomal amphotericin B and caspofungin prophylaxis strategies did not differ in terms of invasive fungal infection rate, patients receiving prophylaxis with liposomal amphotericin B had a reduced ICU stay and an improved Th2 status, as well as a reduced number of post-transplant bacterial infections. Further studies are required to better address and evaluate these findings.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Caspofungin; Chemoprevention; Echinocandins; Female; Follow-Up Studies; Fungemia; Humans; Immunocompromised Host; Length of Stay; Lipopeptides; Liver Transplantation; Male; Middle Aged; Random Allocation; Treatment Outcome

Cryptococcosis is a potentially severe infection that usually occurs in a setting of immunosuppression. Its occurrence outside of this context is rare. We report a case of disseminated cryptococcosis revealed by a spectacular skin disease in an immunocompetent patient.. A 40-year-old male patient had been presenting multiple nodules and tumors on his face for one month in a context of asthenia and intermittent fever. Histological examination of a skin biopsy revealed encapsulated yeasts strongly suggestive of Cryptococcus neoformans. Mycological examination of the skin biopsy and cerebrospinal fluid isolated Cryptococcus gattii. The blood cultures were positive. Brain MRI demonstrated cryptococcal parenchymal involvement. Screening for primary or secondary immunodeficiency was negative. The patient received amphotericin B 1mg/kg/day and fluconazole 600mg/day but died 2months after diagnosis.. Cryptococcosis is a potentially severe infection caused by C. neoformans. This rare condition occurs most commonly in patients with profound deficiency in terms of cellular immunity. Although rare, the occurrence of cryptococcosis in immunocompetent patients is possible, and in this event the signs are highly polymorphic, which usually makes it very difficult to diagnose. The diagnosis of cryptococcosis is based on the identification by direct examination and after staining with India ink of encapsulated yeasts of the Cryptococcus genus. Culture on Sabouraud medium is essential for identification of the species. Treatment for disseminated cryptococcosis involves amphotericin B, often associated with flucytosine IV. In the event of meningitis infection in non-HIV patients, mortality continues to be around 15%, despite adequate medical treatment.. Although rare, cryptococcosis can occur in immunocompetent subjects. The prognosis is severe even after treatment.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus gattii; Facial Dermatoses; Fatal Outcome; Fluconazole; Fungemia; Humans; Immunocompetence; Male; Meningitis, Cryptococcal

Cryptococcus neoformans is a common fungus found throughout the environment that causes opportunistic disease in immunocompromised individuals. Infection of humans with C neoformans usually manifests as lung disease through inhalation of spores or meningoencephalitis by involvement of the central nervous system. Rarely, dissemination in the form of cutaneous lesions can occur in individuals with long term immunosuppression. We present a patient with C. neoformans manifesting as cellulitis with focal segmental glomerulosclerosis treated with corticosteroids. Because of the mortality associated with disseminated cryptococcosis, early identification, especially of atypical cutaneous presentations is critical from a dermatological perspective.

Topics: Amphotericin B; Antifungal Agents; Cellulitis; Cryptococcosis; Cryptococcus neoformans; Cyclosporine; Fluconazole; Flucytosine; Fungemia; Glomerulosclerosis, Focal Segmental; Humans; Immunocompromised Host; Immunosuppressive Agents; Leg Dermatoses; Male; Middle Aged; Prednisone; Skin

Saprochaete capitata (formerly known as Geotrichum capitatum and Blastoschizomyces capitatus) is a rare invasive fungal agent that may lead to mortal clinical course in patients with hematological malignancies. This agent can be colonized in skin, lungs and intestines, and it can cause major opportunistic infections. Invasive systemic infections due to S.capitata have been reported in immunosuppressed patients. In this report, two patients with invasive S.capitata infections detected during the course of persistent neutropenic fever in acute leukemia, were presented. In both cases empirical caspofungin was added to the treatment, as no response was obtained by board-spectrum antibacterial therapy in neutropenic fever. In the first patient, there were no significant findings except the chronic inflammation observed in the biopsies which was performed for the symptoms of lymphadenitis, myositis, and hepatosplenic candidiasis. While persistent fever was on going, S.capitata was isolated from the blood and catheter cultures. There was no response after catheter removing and the introduction of amphotericin B and voriconazole therapy, therefore allogeneic stem cell transplantation plan for the second time for bone marrow aplasia was taken an earlier time. However, the patient died due to progressive pericardial and pleural effusion and multiorgan failure, although an afebrile process after stem cell transplantation could be obtained. Similarly the second patient had persistent fever despite empirical caspofungin treatment. The additional symptoms of diarrhea, abdominal pain and subileus have indicated an intraabdominal infection. During the follow up, S.capitata was isolated from the blood and catheter cultures. Catheter was removed and amphotericin B was initiated. No response was obtained, and voriconazole was added to treatment. Despite of an afebrile and culture-negative period, the patient died as a result of Acinetobacter sepsis and multiorgan failure. Minimal inhibitory concentration values for both of the Saprochete strains were found as 0.25 µg/ml for amfoterisin B, 1 µg/ml for flukonazol, 0.125 µg/ml for vorikonazol and 0.25 µg/ml for itrakonazol. Virulence model was created by injecting the isolates to the Galleria mellonella larvae, and the life cycle of the larvae were determined. The observation revealed that the infected larvae began to die on the second day and there was no live larvae remained on the eleventh day. In conclusion, S.capitata sho

Topics: Adult; Amphotericin B; Animals; Antifungal Agents; Caspofungin; Catheter-Related Infections; Echinocandins; Fatal Outcome; Female; Fungemia; Humans; Leukemia; Lipopeptides; Moths; Mycoses; Opportunistic Infections; Saccharomycetales; Voriconazole; Young Adult

Topics: Adolescent; Amphotericin B; Antifungal Agents; Bone Marrow; Diagnosis, Differential; Fever of Unknown Origin; Fungemia; Histoplasma; Histoplasmosis; Humans; Infusions, Intravenous; Kidney Transplantation; Lung Diseases, Interstitial; Lymphohistiocytosis, Hemophagocytic; Male; Pancytopenia; Transplant Recipients

Although guidelines for the treatment of Malassezia furfur fungemia are not yet defined, clinical data suggest that amphotericin B (AmB) is effective for treating systemic infections. In the absence of clinical breakpoints for Malassezia yeasts, epidemiological cut-off values (ECVs) are useful to discriminate between isolates with and without drug resistance. This study aimed to compare the distribution of minimal inhibitory concentration (MIC) and the ECVs for AmB of both deoxycholate (d-AmB) and liposomal (l-AmB) formulations of M. furfur isolates. The 84 M. furfur strains analyzed, which included 56 from blood, sterile sites and catheters, and 28 from skin, were isolated from patients with bloodstream infections. MICs were determined by the modified broth microdilution method of the Clinical and Laboratory Standards Institute (CLSI). The l-AmB MIC and the ECVs were two-fold lower than those of d-AmB and a lower l-AmB mean MIC value was found for blood isolates than from skin. The ECVs for l-AmB and d-AmB were 8 mg/l and 32 mg/l, respectively. Three strains (3.6%) showed l-AmB MIC higher than ECV (MIC > 8 mg/l) of which two were isolated from the catheter tip of patients treated with micafugin, l-Amb and fluconazole, and one from skin. The results showed that the l-AmB might be employed for assessing the in vitro antifungal susceptibility of M. furfur by a modified CLSI protocol and that ECVs might be useful for detecting the emergence of resistance.

Topics: Amphotericin B; Antifungal Agents; Blood; Catheters; Deoxycholic Acid; Drug Combinations; Fungemia; Humans; Malassezia; Microbial Sensitivity Tests; Skin

We report a case of invasive infection due to Saprochaete capitata in a patient with hematological malignancies after chemotherapy treatment and empiric antifungal therapy with caspofungin. Although severely immunocompromised the patient survived been treated with amphotericin B lipid complex associated with voriconazole.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Caspofungin; Echinocandins; Fungemia; Hematologic Neoplasms; Humans; Lipopeptides; Lung; Male; Microbial Sensitivity Tests; Microbiological Techniques; Microscopy; Radiography, Thoracic; Saccharomycetales; Treatment Outcome; Voriconazole

Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving >40 days who engrafted and were discharged without prior IFD. All patients who received ⩾20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to construct a post-engraftment IFD risk score. The 1-year CI of IFD was 11%. The non-relapse mortality was 40% in those developing IFD and 16% in those who did not. The intent-to-treat analysis showed that 17% of patients abandoned the assigned prophylaxis. Age >40 years, ⩾1 previous SCT, pre-engraftment neutropenia >15 days, extensive chronic GVHD and CMV reactivation were independent risk factors. The post-engraftment IFD score stratified patients into low risk (0-1 factor, CI 0.7%), intermediate risk (2 factors, CI 9.9%) and high risk (3-5 factors, CI 24.7%) (P<0.0001). The antifungal prophylaxis strategy failed to prevent post-engraftment IFD in 11% of alloSCT. Our risk score could be useful to implement risk-adapted strategies using antifungal prophylaxis after engraftment.

Topics: Administration, Oral; Adult; Aged; Allografts; Amphotericin B; Antifungal Agents; Aspergillosis; Caspofungin; Cause of Death; Drug Therapy, Combination; Echinocandins; Female; Fungemia; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Incidence; Lipopeptides; Male; Medication Adherence; Middle Aged; Mycoses; Neutropenia; Patient Compliance; Premedication; Retrospective Studies; Risk Assessment; Risk Factors; Survival Analysis; Transplantation Conditioning; Treatment Failure; Triazoles; Young Adult

Our case series showed that uncomplicated Yarrowia lipolytica fungemia might be treated with catheter removal alone. The Vitek 2 YST identification (ID) card system, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and internal transcribed spacer and 25S nuclear ribosomal DNA (nrDNA) gene sequencing provided reliable identification. All isolates had low MICs to voriconazole, echinocandins, and amphotericin B.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Base Sequence; Catheter-Related Infections; Catheterization, Central Venous; Catheterization, Peripheral; Child, Preschool; DNA, Ribosomal Spacer; Echinocandins; Female; Fungemia; Hospitalization; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Sequence Data; Prospective Studies; Sequence Analysis, DNA; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Voriconazole; Yarrowia

Topics: Adult; AIDS Serodiagnosis; Amphotericin B; Antifungal Agents; Fungemia; Histoplasma; Histoplasmosis; HIV Infections; Humans; Male; Skin

The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient's risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information.

Topics: Amphotericin B; Antifungal Agents; Candidiasis, Invasive; Catheter-Related Infections; Chemotherapy-Induced Febrile Neutropenia; Clinical Trials as Topic; Combined Modality Therapy; Drug Monitoring; Drug Therapy, Combination; Echinocandins; Fungemia; Humans; Immunocompromised Host; Immunotherapy; Invasive Pulmonary Aspergillosis; Mycoses; Neoplasms; Salvage Therapy; Triazoles

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

Despite being considered an emerging yeast related to immunocompromised individuals, severe infections by Malassezia furfur have not been evaluated. During a one-year survey on yeasts fungemia, 290 neonatal and 17 pediatric patients with intravascular catheters, lipid parenteral nutrition, prolonged ward stay, and surgery were enrolled. In addition, the origin of the infection was investigated by swabbing hand skin of patients, parents, and healthcare workers and medical devices. All biological specimens and swabs were cultured on Sabouraud dextrose agar and Dixon agar. The yeasts identification was based on morphological and biochemical features and by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and confirmed by sequencing the internal transcribed spacer of nuclear ribosomal DNA. A higher prevalence of M. furfur (2.1%) over Candida spp. (1.4%) caused bloodstream infections (BSIs). Twelve fungemia episodes were recorded: 2 by M. furfur in a pediatric ward and 10 in a neonatal intensive care unit (6 caused by M. furfur and 4 by Candida spp.). M. furfur was also isolated from the skin of all patients with BSIs, from the hand skin of a parent, and from an incubator surface and sheet. Patients with Candida spp. and M. furfur BSIs were successfully treated with intravenous liposomal Amphotericin B. These findings highlight the need for a more accurate etiological diagnosis in high-risk patients by adding lipid-supplemented culture media for Malassezia in the current mycological routine as the clinical features, patient management, and outcomes in both Candida and Malassezia fungemia do not differ.

Topics: Adolescent; Amphotericin B; Candida; Child; Child, Preschool; Critical Care; DNA, Fungal; Female; Fungemia; Humans; Infant; Infant, Newborn; Malassezia; Male; Microbiological Techniques; Molecular Sequence Data; Prevalence; Sequence Analysis, DNA; 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

Topics: Adult; Amphotericin B; Antifungal Agents; Blood Specimen Collection; CD4 Lymphocyte Count; Diagnosis, Differential; Erythrocytes, Abnormal; Fungemia; Histoplasma; Histoplasmosis; HIV Infections; Humans; Itraconazole; Male; Viral Load

Acremonium species are filamentous, cosmopolitan fungi frequently isolated from plant debris and soil that have emerged as an important cause of morbidity and mortality in immunocompromised patients. We present data from two hematologic malignancy patients with Acremonium fungemia who had refractory disease despite initial treatment with Amphotericin B with clinical response after changing therapy to Voriconazole. Acremonium should be considered in the differential diagnosis of patients with clinical presentation suggestive of fungal infection and special attention should be given to the treatment challenge it represents.

Topics: Acremonium; Aged; Amphotericin B; Antifungal Agents; Diagnosis, Differential; Female; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Treatment Outcome; Voriconazole

Scedosporium prolificans (S. prolificans) is a type of mold, which rarely affects immunocompromised people. We treated a 71-year-old woman with acute myeloid leukemia (AML-M5a) with low-dose cytarabine, acralubicin, and filgrastim as the induction therapy. On day 7 after the initiation of chemotherapy, she became febrile and agranulocytic, and developed anal pain ; therefore, we discontinued the chemotherapy on day 8. Broad-spectrum antibiotics, micafungin, and then liposomal amphotericin B were ineffective. The serum concentration of β-D-glucan was 525 pg/mL. She died of multiple organ failure on day 17. S. prolificans was detected from the blood culture on day 13. Physicians should consider Scedosporium spp. infection when principal antifungal agents are ineffective and fungal infection is strongly suspected.

Topics: Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Biomarkers; Echinocandins; Fatal Outcome; Female; Fungemia; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lipopeptides; Micafungin; Multiple Organ Failure; Scedosporium; Treatment Failure

Rhodotorula is a ubiquitous yeast that can infect immunocompromised patients. Here, we present the case of a 45-year-old patient with AIDS who developed a Rhodotorula mucilaginosa fungemia. The patient had a past history of visceral leishmaniasis (VL) and was hospitalised to receive chemotherapy for a B-cell lymphoma of the sinonasal cavities. The patient had no fever and no signs of VL. A systematic research for Leishmania by blood and bone marrow cultures was made and he received liposomal amphtotericin B (3 mg/kg in a single dose) to prevent a VL relapse. Rhodotorula fungemia was accidentally detected after 17 days of blood culture using a specific medium for leishmaniasis diagnosis. This long culture incubation time was probably facilitated by amphotericin B treatment. Rhodotorula is an emerging pathogen that may escape detection due its slow growth in culture.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Culture Media; Fungemia; Humans; Leishmaniasis, Visceral; Lymphoma, AIDS-Related; Male; Middle Aged; Rhodotorula

The efficacy of polyene macrolides to treat experimental Trichosporon bloodstream infection was evaluated by histopathological examination and viable cell counts in the kidneys of infected mice. Viable cell counts on the 5th day after infection confirmed that liposomal amphotericin B (L-AMB) is a more effective treatment than fluconazole (FLC) for mice infected with an azole-resistant strain of Trichosporon. Histological examination revealed that the administration of L-AMB induced a transformation from acute purulent inflammation caused by both azole-susceptible and -resistant strain infections to a chronic and subsiding form, whereas FLC failed to convert the acute inflammation induced by the azole-resistant strain to a subsiding form. Our results demonstrate that polyene macrolides can be used as an alternative therapy for infection of azole-resistant strains of Trichosporon and that histopathological evaluation is useful for elucidating the pathophysiology of an experimental Trichosporon infection.

Topics: Amphotericin B; Animals; Antifungal Agents; Colony Count, Microbial; Disease Models, Animal; Fluconazole; Fungemia; Histocytochemistry; Kidney; Macrolides; Male; Mice; Microbial Viability; Polyenes; Trichosporon; Trichosporonosis

There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given sequentially after mold-active azoles due to a possible antagonism in their antifungal mechanism. To investigate this possible effect in the clinic, we retrospectively studied 182 high risk hematologic patients with invasive fungal infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.7%) had possible, 52 (28.6%) probable and 34 (18.7%) proven IFI according to EORTC classification. Most had suspected or proven invasive aspergillosis. We compared patients with prior exposure to mold-active azoles (n=100) to those having not (n=82). The group with prior mold-active azoles included more patients with poor risk features for IFI as acute myeloid leukemia (p<0.05) and prolonged neutropenia (p<0.05). A favorable response in the IFI, defined as a complete or partial response, was achieved in 75% and 74.4% of patients in the whole cohort, and in 66% and 74.4% of patients with probable or proven IFI in the two groups. None of these differences were significant. Multivariate analysis showed that refractory baseline disease and renal dysfunction were adverse factors for response in the IFI (p<0.05). Survival was poorer for patients with prior broad spectrum azoles (p<0.05), and for those who did not recover from neutropenia (p<0.05). In conclusion, the effectiveness of treatment of breakthrough fungal infection with L-AmB is not likely to be affected by prior exposure to mold-active azoles prophylaxis, but survival largely depends on host and disease factors.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Candidiasis, Invasive; Child; Child, Preschool; Combined Modality Therapy; Cross Infection; Drug Evaluation; Female; Fungemia; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Male; Middle Aged; Myelodysplastic Syndromes; Neutropenia; Postoperative Complications; Retrospective Studies; Risk; Transplantation, Homologous; Treatment Outcome; Triazoles; Young Adult

Aggressive chemotherapy and immunosuppressive treatment may prolong patients' life, but influence the risk of severe, life-threatening infections. Here, we report the case of a 21-year-old caucasian female who developed a disseminated infection of Scedosporium prolificans after allogenic stem cell transplantation performed for treatment of relapsed acute lymphoblastic leukaemia. The pathogen was isolated from the blood and identified on the basis of its macroscopic and microscopic morphological features. The empirical treatment with amphotericin B provided no improvement. However, introduction of intravenous voriconazole resulted in amelioration of fever. Unfortunately, the patient died due to progression of underlying disease and multiorgan failure. However, this case report indicates a possible relevance of voriconazole-based treatment regimens in invasive S. prolificans infections.

Topics: Allografts; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Drug Substitution; Fatal Outcome; Female; Fluconazole; Fungemia; Graft vs Host Disease; Humans; Immunocompromised Host; Immunosuppressive Agents; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Scedosporium; Triazoles; Voriconazole; Young Adult

Blastoschizomyces capitatus is a rare fungal pathogen that may lead to severe and fatal systemic infections especially in immunosuppressive individuals. B.capitatus strains have also been reported as the cause of hospital-acquired infections and outbreaks. In this report, three fungemia cases caused by B.capitatus with hematologic malignancies have been presented. The first case was a 20-year-old female with acute lymphoblastic leukemia, the second was a 26-year-old female with B-cell malignant lymphoma and the third was a 7-year-old male with B-cell acute lymphoblastic leukemia. All of the patients have been receiving chemotherapy, and treated with antibacterial and antifungal agents due to neutropenia. The blood cultures obtained from the second and third patients yielded B.capitatus although they were under empirical caspofungin therapy. Those patients have been treated with voriconazole and amphotericin B after the identification of B.capitatus, and clinical improvement were noted during their follow-up. However the first patient who was also under caspofungin therapy had died just before the isolation of B.capitatus from her blood culture. Conventional mycological methods [macroscopic and microscopic morphology, germ tube test, urea hydrolysis, carbohydrate assimilation tests (API 20C AUX; BioMerieux, France), growth temperature, cycloheximide sensitivity] were used for the identification of the isolates. The strains were identified as B.capitatus with the characteristics of annelloconidia formation, urease negativity, carbohydrate utilization, growth at 45°C and resistance to cycloheximide. Antifungal susceptibilities of isolates were determined by using microdilution method (for amphotericin B, fluconazole, itraconazole, voriconazole, ketoconazole) and E-test (for caspofungin). Minimum inhibitory concentration (MIC) values of the three B.capitatus strains were detected as 0.25, 0.125, 0.032 µg/ml for amphotericin B; 2, 2, 16 µg/ml for fluconazole; 0.064, 0.032, 0.032 µg/ml for itraconazole and 0.125, 0.064, 0.064 µg/ml for ketoconazole, respectively, while MIC values of all strains were 0.032 µg/ml for voriconazole and > 32 µg/ml for caspofungin. Since B.capitatus strains were isolated from the cases within about 15 days -sequentially-, the genotypes of the isolates were determined by repetitive sequence-based PCR (DiversiLab System; BioMerieux, France) to investigate the similarity rates. The results of analysis indicated 97% similarity between tw

Topics: Adult; Amphotericin B; Antifungal Agents; Caspofungin; Child; Echinocandins; Female; Fungemia; Humans; Immunocompromised Host; Lipopeptides; Lymphoma, B-Cell; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Saccharomycetales; Triazoles; Voriconazole; Young Adult

Rhodotorula species are emergent fungal pathogens capable of causing invasive infections, primarily fungemia. They are particularly problematic in immunosuppressed patients when using a central venous catheter. In this study, we evaluated the species distribution of 51 clinical and 8 environmental Rhodotorula species isolates using the ID32C system and internal transcribed spacer (ITS) sequencing. Antifungal susceptibility testing and biofilm formation capability using a crystal violet staining assay were performed. Using ITS sequencing as the gold standard, the clinical isolates were identified as follows: 44 R. mucilaginosa isolates, 2 R. glutinis isolates, 2 R. minuta isolates, 2 R. dairenensis isolates, and 1 Rhodosporidium fluviale isolate. The environmental isolates included 7 R. mucilaginosa isolates and 1 R. slooffiae isolate. Using the ID32C system, along with a nitrate assimilation test, only 90.3% of the isolates tested were correctly identified. In the biofilm formation assay, R. mucilaginosa and R. minuta exhibited greater biofilm formation ability compared to the other Rhodotorula species; the clinical isolates of R. mucilaginosa showed greater biofilm formation compared to the environmental isolates (P = 0.04). Amphotericin B showed good in vitro activity (MIC ≤ 1 μg/ml) against planktonic cells, whereas voriconazole and posaconazole showed poor activity (MIC(50)/MIC(90), 2/4 μg/ml). Caspofungin and fluconazole MICs were consistently high for all isolates tested (≥64 μg/ml and ≥ 4 μg/ml, respectively). In this study, we emphasized the importance of molecular methods to correctly identify Rhodotorula species isolates and non-R. mucilaginosa species in particular. The antifungal susceptibility profile reinforces amphotericin B as the antifungal drug of choice for the treatment of Rhodotorula infections. To our knowledge, this is the first study evaluating putative differences in the ability of biofilm formation among different Rhodotorula species.

Topics: Amphotericin B; Antifungal Agents; Biofilms; DNA, Ribosomal Spacer; Fungemia; Gentian Violet; Humans; Microbial Sensitivity Tests; Microbial Viability; Microscopy, Electron, Scanning; Phylogeny; Plankton; Rhodotorula; Sequence Analysis, DNA; Soil Microbiology; Species Specificity

Recently, geographic variations in resistance to agents commonly used in the treatment of cryptococcosis have been reported. Therefore, the antifungal susceptibilities of 31 clinical isolates of Cryptococcus neoformans, collected in Serbia during 10-year period, were investigated. Strains were isolated from cerebrospinal fluid (n=28) and blood (n=3), from patients with AIDS (n=26), lymphoma (n=4) and kidney transplant recipient (n=1). The minimal inhibitory concentrations (MICs) of amphotericin B, 5-fluorocytosine, fluconazole and itraconazole were determined by the E-test(®) method. The isolates were highly susceptible to amphotericin B (100% susceptibility at MIC<0.5 μg/mL) and 5-fluorocytosine (87.1% susceptibility at MIC ≤ 4 μg/mL). Geometric mean MIC of amphotericin B and 5-fluorocytosine were 0.102 μg/mL and 0.396 μg/mL, respectively. Fluconazole exhibited the lowest activity in vitro (48.4% susceptibility at MIC ≤ 8 μg/mL) with a significant resistance rate. The activity of itraconazole was also decreased (48.4% susceptibility at MIC ≤ 0.25 μg/mL). The geometric mean MIC of fluconazole stood at 15.14 μg/mL and of itraconazole was 0.144 μg/mL. Cross-resistance among azoles was not common (3.2%), but the parallel increase in fluconazole and itraconazole MIC has been observed (P<0.01). The low rate of susceptibility to fluconazole stresses the need for active antifungal surveillance of C. neoformans and of the corresponding data from different geographic regions.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cerebrospinal Fluid; Cross Infection; Cryptococcosis; Cryptococcus neoformans; Drug Resistance, Multiple, Fungal; Fluconazole; Flucytosine; Fungemia; Humans; Itraconazole; Kidney Transplantation; Lymphoma; Meningitis, Cryptococcal; Microbial Sensitivity Tests; Postoperative Complications; Serbia

Cryptococcosis is an important systemic mycosis caused by members of the Cryptococcus neoformans species complex. This disease is potentially fatal in various animals, including koalas. We describe the long-term surveillance and treatment of subclinical cryptococcosis and nasal colonization of koalas by Cryptococcus neoformans and C. gattii. Of the 15 animals investigated through the use of samples obtained by nasal swabs, antigen titer measurements, and pathologic examination, C. neoformans was found associated with nine koalas and C. gattii with one animal. Nine koalas showed subclinical disease and one clinical infections and antigenemia. Treatment with fluconazole, itraconazole and amphotericin B upon detection of C. neoformans or C. gattii was not effective. The results of the present study showed that C. neoformans was the predominant species isolated from the nasal swab samples and the fungus might have naturally become associated with the koalas' nasal cavities at Kanazawa Zoological Gardens. The unclear treatment effectiveness might have been caused by a shorter treatment period that is routinely used and unstable itraconazole absorption. This investigation also underscores the need for identifying effective treatment regimens for subclinical cryptococcosis and efficient measures for eradicating C. neoformans and C. gattii in koalas.

Topics: Amphotericin B; Animals; Animals, Zoo; Antifungal Agents; Carrier State; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Female; Fluconazole; Fungemia; Itraconazole; Male; Nasal Cavity; Phascolarctidae; Treatment Outcome

The detection of serum 1,3-β-d-glucan (BDG) has been reported to be useful for the diagnosis and therapeutic monitoring of various invasive fungal infections. Although Trichosporon fungemia is increasingly recognized as a fatal mycosis in immunocompromised patients, the utility of this assay for Trichosporon fungemia is still unknown. In our experience (28 cases), the level of BDG rose in about half of the patients with hematologic disorders who developed Trichosporon fungemia. Among them, early death from this infection was more frequently seen in BDG-negative patients than in BDG-positive patients. In addition, overall survival was also significantly worse in BDG-negative patients than in BDG-positive patients. There were no significant differences between these two patient groups in terms of clinical background. Unlike for other invasive fungal infections, elevation of BDG level may indicate a paradoxical sign for Trichosporon fungemia in patients with hematologic disorders.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; beta-Glucans; Echinocandins; Female; Fluconazole; Fungemia; Hematologic Diseases; Humans; Immunocompromised Host; Lipopeptides; Male; Micafungin; Miconazole; Middle Aged; Proteoglycans; Retrospective Studies; Treatment Outcome; Trichosporon; Young Adult

Trichosporon fungemia is a rare and fatal fungal infection that occurs in patients with prolonged neutropenia associated with hematologic malignancies. A 21-year-old male developed Trichosporon fungemia during remission induction therapy for acute myeloid leukemia (AML). Although two courses of induction therapy failed to induce a remission of AML, combination therapy with voriconazole and liposomal amphotericin B (L-AmB) followed by monocyte colony-stimulating factor ameliorated the Trichosporon fungemia and enabled the patient to receive reduced-intensity bone marrow transplantation (BMT) from his human leukocyte antigen-A one-locus mismatched mother. The patient achieved a durable remission after BMT without exacerbation of Trichosporon fungemia. The combination therapy with voriconazole and L-AmB may therefore be useful in controlling Trichosporon fungemia associated with prolonged neutropenia after remission induction therapy for AML.

Topics: Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Drug Therapy, Combination; Fatal Outcome; Fungemia; Humans; Leukemia, Myeloid, Acute; Male; Pyrimidines; Triazoles; Trichosporon; Trichosporonosis; Voriconazole; Young Adult

Blastoschizomyces capitatus is a rare fungal pathogen that may lead to fatal infections especially in immunosuppressive individuals. In this report, three cases of B.capitatus were presented. The patients were under treatment for acute myeloid leukemia and their blood cultures yielded B.capitatus. The patients clinical conditions deteriorated and they died despite amphotericin B treatment. The isolates were identified by conventional mycological methods and API 20C AUX (Bio-Mérieux, France) system. Antifungal susceptibility test of the strains was performed with Sensititre Yeast One Panel (Trek Diagnostic Systems, USA) and minimum inhibitory concentration (MIC) ranges for amphotericin B, caspofungin, fluconazole, itraconazole, voriconazole, posaconazole, and flucytosine were found as 0.5-1; > 16; 8-16; 0.5; 0.25; 0.5-1 and 0.06-0.25 µg/ml, respectively. Isolated strains were genotyped with RAPD-PCR (Random Amplified Polymorphic DNA-Polymerase Chain Reaction) using Cnd-3, Cnd-4, OPE-03, OPE-18 primers. The strains isolated from the first two cases were found to be genotypically identical, while the strain isolated from the third case was different. Genotypically identical isolates belonged to two patients who were admitted to the hospital with approximately 18 months interval. The other strain with a unique genotype, was isolated from a patient who was admitted to the hospital about two years later than the other two patients. In conclusion, B.capitatus should be considered as an important opportunistic pathogen especially in patients with hematologic malignancies. The data of this study demonstrated that the lowest MIC values for B.capitatus strains were with voriconazole.

Topics: Amphotericin B; Antifungal Agents; Fatal Outcome; Female; Fungemia; Genotype; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction; Random Amplified Polymorphic DNA Technique; Saccharomycetales

Topics: Adolescent; Amphotericin B; Antifungal Agents; Cellulitis; Cranial Nerve Diseases; Delayed Diagnosis; Diabetes Complications; Disease Progression; Disease Susceptibility; Encephalitis; Fatal Outcome; Female; Fungemia; Humans; Male; Middle Aged; Mucormycosis; Multiple Organ Failure; Opportunistic Infections; Sinusitis; Vision Disorders

Saccharomyces cerevisiae, known as baker's yeast, is normally considered a non-pathogenic yeast. A genetically very similar subtype, S boulardii, is used in a probioticum (Sacchaflor) to prevent antibiotic-associated diarrhoea and in the treatment of recurrent Clostridium difficile associated diarrhoea. The authors present a case report of a 79-year-old woman with rheumatoid arthritis, who after a bowel resection developed S boulardii fungemia. Her postoperative course was complicated by nutritional problems, anaemia and several nosocomial infections including recurrent C difficile associated diarrhoea. The diarrhoea was treated with metronidazole, vancomycin and Sacchaflor. After 13 days of treatment, the patient developed fungemia with S boulardii. Treatment with Sacchaflor was immediately discontinued and the patient was successfully treated with amphotericin B. Fungemia is a rare, but a serious complication to treatment with probiotics. Accordingly, the authors find it important to remind the clinicians of this risk when prescribing probiotics especially to immunocompromised patients.

Topics: Aged; Amphotericin B; Antifungal Agents; Enterocolitis, Pseudomembranous; Female; Fungemia; Humans; Probiotics; Saccharomyces

Topics: Accidental Falls; Accidents, Traffic; Aged, 80 and over; Amphotericin B; Amputation, Surgical; Antifungal Agents; Combined Modality Therapy; Debridement; Fatal Outcome; Female; Fractures, Bone; Fractures, Open; Fungemia; Humans; Humeral Fractures; Immunocompetence; Lacerations; Middle Aged; Mucormycosis; Multiple Trauma; Opportunistic Infections; Postoperative Complications; Recovery Room; Splenectomy; Splenic Rupture; Thigh; Transfusion Reaction; Wound Infection

To date, there have been several case reports of Rhodotorula infection in haematological patients, but none affecting patients with multiple myeloma (MM). We describe a 54-year-old man with MM receiving prophylaxis with fluconazole who was using a subclavian Port-A-Cath and presented two episodes of fungaemia caused by Rhodotorula mucilaginosa. The first episode was resolved with oral itraconazole and neutropenia recovery. During the second episode, caspofungin was administered without success; however, liposomal amphotericin B and catheter withdrawal resolved the fungaemia. As far as we know, this is the first case reported of R. mucilaginosa fungaemia in a patient with MM.

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Catheter-Related Infections; Echinocandins; Fungemia; Humans; Itraconazole; Lipopeptides; Male; Middle Aged; Multiple Myeloma; Rhodotorula; Treatment Outcome

This report describes a chronically ill child who presented with high fever and was diagnosed with catheter-related sepsis. Aureobasidium pullulans variety melanigenum, a dematiaceous fungus that rarely causes opportunistic infections, was recovered from multiple blood cultures. Antifungal susceptibilities were performed and the minimum inhibitory concentration (MIC) for fluconazole was 64 mg/l, suggestive of fluconazole resistance. The patient made a full recovery after removal of the catheter line and treatment with liposomal amphotericin B. This is the first case report of an elevated in vitro fluconazole MIC of an A. pullulans isolate and only the third case of successful treatment of A. pullulans fungemia.

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Blood; Catheter-Related Infections; Child; DNA, Fungal; DNA, Ribosomal Spacer; Drug Resistance, Fungal; Fluconazole; Fungemia; Humans; Male; Microbial Sensitivity Tests; Molecular Sequence Data; Mycoses; Sequence Analysis, DNA

Topics: Aged; Amphotericin B; Anticoagulants; Antifungal Agents; Cellulitis; Cryptococcosis; Dermatomycoses; Fatal Outcome; Female; Fungemia; Heparin, Low-Molecular-Weight; Hepatitis, Autoimmune; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Cirrhosis; Lung Diseases, Fungal; Necrosis; Prednisone; Radiography; Thrombophilia

Topics: Amphotericin B; Biopsy, Needle; Follow-Up Studies; Foot Dermatoses; Fungemia; Fusarium; Humans; Immunocompromised Host; Immunohistochemistry; Leukemia, Myeloid; Magnetic Resonance Imaging; Male; Middle Aged; Muscular Diseases; Mycoses; Opportunistic Infections; Risk Assessment; Severity of Illness Index; Toes; Treatment Outcome

Topics: Abdominal Pain; Adult; Amphotericin B; Antifungal Agents; Chills; Diagnosis, Differential; Female; Fever; Fluconazole; Flucytosine; Fungemia; Headache; Humans; Nausea; Pyrimidines; Recurrence; Saccharomyces cerevisiae; Triazoles; Voriconazole

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

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Fungemia; Humans; Pyrimidines; Stem Cell Transplantation; Transplantation, Homologous; Triazoles; Voriconazole

In routine laboratory practice, the determination of MICs of antifungals for yeasts often relies on the Etest, because of a good correlation with reference methods. However, this correlation was established through predesigned studies, rather than prospective testing. The surveillance programme of fungaemia (YEASTS programme), implemented since 2003, facilitated our comparison of the Etest and the EUCAST results, obtained on a routine basis in nine different hospitals and in a reference laboratory, respectively. The analysis included 690 isolates recovered from blood culture (362 Candida albicans, 113 Candida glabrata, 69 Candida parapsilosis, 55 Candida tropicalis, 31 Cryptococcus neoformans, and 60 other yeast species) that were tested for their susceptibility to amphotericin B (n = 655), fluconazole (n = 669), itraconazole (n = 198), voriconazole (n = 588), flucytosine (n = 314), and caspofungin (n = 244). Agreement between the Etest and EUCAST datasets was calculated and categorized on the basis of previously published breakpoints. The level of agreement at ±2 dilutions was 75% for amphotericin B and 90% for flucytosine; for the azoles, it ranged from 71% for itraconazole to 87% for voriconazole. No significant difference was observed among the yeast species, except for Cryptococcus neoformans and flucytosine, with an agreement <40%. Categorical agreement ranged from 60% for itraconazole to 90% for flucytosine. Major and very major discrepancies occurred in <12% and 6%, respectively. The Etest, even when performed on a routine basis, shows a ≥71% agreement with the EUCAST reference method.

Topics: Amphotericin B; Antifungal Agents; Candida; Caspofungin; Cryptococcus neoformans; Drug Resistance, Fungal; Echinocandins; Fluconazole; Flucytosine; Fungemia; Itraconazole; Laboratories, Hospital; Lipopeptides; Microbial Sensitivity Tests; Pyrimidines; Reference Values; Triazoles; Voriconazole; Yeasts

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

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; Fungemia; Humans; Male; Young Adult

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

During the past two decades, an increasing number of unusual moulds has been reported as responsible for septicaemia and systemic or disseminated infections in immunocompromised patients. Investigation of fever in a 10-year-old boy with acute myeloblastic leukaemia, including blood cultures on selective media, allowed the diagnosis of a fungaemia due to the slow-growing fungus Acremonium strictum. The patient recovered with liposomal amphotericin B (AmB) and voriconazole, followed by voriconazole alone due to AmB resistance. Facing a neutropenic patient with fever, clinicians usually suspect bacterial or viral aetiologies. This case, however, illustrates the need for mycological analysis of blood samples in febrile neutropenic patients and for antifungal susceptibility testing.

Topics: Acremonium; Amphotericin B; Antifungal Agents; Blood; Child; Fever; Fungemia; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Neutropenia; Pyrimidines; Triazoles; Voriconazole

The liposomal formulation of amphotericin B (LAmB) has been shown to cause few and mild infusion-related reactions, while achieving high plasma and tissue concentrations compared with conventional amphotericin B. We investigated the efficacy and safety of high-dose LAmB (7.5 mg/kg once weekly) prophylaxis of fungal infections in allogeneic stem-cell transplanted (allo-SCT) patients with graft-versus-host disease (GvHD).. Retrospective, comparative, single-center.. Forty-two patients receiving high-dose prednisone for GvHD after allo-SCT had LAmB prophylaxis; 83 patients in the control group received other antifungal prophylaxis.. In the LAmB prophylaxis group, the median duration of treatment was 7 weeks. The cumulative incidence of invasive fungal infection was 8% at 1 year after transplantation, 8% at 2 years and 16% at 3 years in the LAmB group vs. 36% at 1 year, 44% at 2 years and 49% at 3 years in the other prophylaxis group (P=.008). Fungal infection-related mortality after transplantation was observed in none of the patients in the LAmB prophylaxis group vs. 12 patients (14%) at 1 year, 14 patients (17%) at 2 years and 16 patients (19%) at 3 years in the control group (P=.005). The tolerance of the treatment was good with only 5 patients (12%) having a reversible nephrotoxicity leading to temporary treatment discontinuation.. High-dose LAmB prophylaxis seems effective and well tolerated in this short series of allo-SCT patients with GvHD. Prospective clinical studies are required to confirm these results.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Drug Administration Schedule; Female; Fungemia; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Prednisolone; Retrospective Studies; Transplantation, Homologous; Young Adult

Topics: Amphotericin B; Antifungal Agents; Candida; Cardiac Surgical Procedures; Child; Drug Resistance, Multiple, Fungal; Fungemia; Humans; Infant; Postoperative Complications; 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

Cryptococcosis is a disseminated fungal disease typically associated with immunosuppression and characterized by high mortality rates. Cryptococcus neoformans has been reported to be isolated from blood cultures in around 20% of patients with cryptococcosis, and cryptococcemia has been correlated with poor prognosis. We report a case of fatal C. neoformans fungemia in a neutropenic patient with a history of chronic lymphocytic leukemia treated with alemtuzumab. The patient presented with loss of consciousness and died after 5 days of antifungal therapy with liposomal amphotericin B. The international literature regarding opportunistic infections after immunosuppressive therapy with alemtuzumab with particular attention on fungal infections has also been reviewed.

Topics: Aged; Alemtuzumab; Amphotericin B; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antifungal Agents; Antineoplastic Agents; Cryptococcosis; Cryptococcus neoformans; Fatal Outcome; Fungemia; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Neutropenia; Opportunistic Infections

Topics: ABO Blood-Group System; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Caspofungin; Drug Therapy, Combination; Echinocandins; Female; Fungemia; Fusarium; Graft Rejection; Histocompatibility; Humans; Immunocompromised Host; Immunosuppressive Agents; Lipopeptides; Liver Transplantation; Meropenem; Middle Aged; Teicoplanin; Thienamycins

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

Topics: Aged; Amphotericin B; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Rheumatoid; Colonic Diseases; Colonoscopy; Female; Follow-Up Studies; Fungemia; Histoplasmosis; Humans; Immunocompromised Host; Infliximab; Risk Assessment; Ulcer

Kodamaea (Pichia) ohmeri is a yeast species that has not been reported to be a frequent cause of human infections. The current report describes a case of fungemia caused by K. ohmeri in a 3-year-old female patient hospitalized in the public hospital Maria Alice Fernandes, Natal, RN, Brazil. The patient had previously received antimicrobial therapy due to a peritoneal infection and nosocomial pneumonia, and had a central venous catheter implanted. Kodamaea ohmeri was isolated from blood and the tip of the catheter, 48 h after its implantation. The yeast was identified by standard microbiological methods and sequence analysis of the D1/D2 domains and the ITS 1 + 2 spacer regions of the ribosomal DNA. On CHROMagar Candida medium, the isolate showed a color change from pink to blue. The yeast was susceptible to amphotericin B, and liposomal AmB was used successfully to clear the infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Catheters, Indwelling; Child; Cross Infection; Female; Fungemia; Hospitals, Public; Humans; Infant, Newborn; Male; Middle Aged; Pichia

Cutaneous cryptococcosis, caused by an encapsulated yeast, Cryptococcus neoformans, is generally associated with concomitant systemic infection. Here we report a case of primary cutaneous cryptococcosis with spread to central nervous system in an HIV seronegative young boy. In the present case, a 17-year-old boy who was suffering from a non-healing ulcer on his right great toe for 5 months, presented with the signs and symptoms of meningitis. Cryptococcus neoformans var. gattii was isolated from the CSF of the patient. Amphotericin B administration produced recovery from the meningitis as well as from the ulcer. This case study suggests that primary cutaneous cryptococcosis can be diagnosed provisionally by a simple Gram stained smear and India ink examination in order to avoid occurrence of disseminated cryptococcosis, including meningial involvement, which may have a fatal outcome.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Carbon; Coloring Agents; Cryptococcosis; Cryptococcus gattii; Dermatomycoses; Fluconazole; Foot Ulcer; Fungemia; Gentian Violet; HIV Seronegativity; Humans; Male; Meningitis, Cryptococcal; Phenazines; Staining and Labeling; Toes

This is the first case reported of central venous catheter-related fungemia due to C. neoformans. A patient with chronic renal failure developed a fungemia during the treatment of a dialysis-associated bacteremia. Cryptococcus neoformans grew in the catheter tip and blood culture. We addressed questions about this catheter-related fungemia.

Topics: Amphotericin B; Antifungal Agents; Catheter-Related Infections; Catheterization, Central Venous; Cryptococcosis; Cryptococcus neoformans; Fatal Outcome; Female; Fungemia; Humans; Kidney Failure, Chronic; Middle Aged; Renal Dialysis

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

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

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

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

Topics: Amphotericin B; Antifungal Agents; Child; Fungemia; Humans; Immunocompetence; Male; Mucorales; Mucormycosis; Plastic Surgery Procedures; Surgical Flaps; Triazoles

In this study the molecular identification and susceptibility profile of 21 clinical isolates, from a Brazilian hospital, belongs to six different species of Trichosporon were described. Trichosporon asahii was the predominant species and corresponded to 43% of isolates. Eighty three percent of the strains isolated from deep sites were identified as T. asahii, while only 17% belong to a non-T. asahii species (Trichosporon inkin). In general, the MICs were high and independent of the species of Trichosporon as well as the clinical origin of strain. Amphotericin B and fluconazole were less effective against Trichosporon spp. and high MIC values of voriconazole, posaconazole and ravuconazole were observed. Fifty-six percent (5/9) of T. asahii strains were isolated from deep sites, whereas 8% (1/12) of non-T. asahii species were isolated from those sites. A total of 89% of T. asahii isolates exhibited resistance to amphotericin B in vitro.

Topics: Amphotericin B; Antifungal Agents; Brazil; Cross Infection; Dermatomycoses; Drug Resistance, Fungal; Echinocandins; Female; Flucytosine; Fungemia; Hospitals, University; Humans; Mycological Typing Techniques; Mycoses; Onychomycosis; Opportunistic Infections; Organ Specificity; Triazoles; Trichosporon; Urine; Vaginitis

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

A 47-year-old man with newly diagnosed acute myeloblastic leukemia and non-insulin-dependent diabetes mellitus developed Trichosporon asahii fungemia while receiving caspofungin as empirical antifungal therapy. The diagnosis was based on repeated isolation of T. asahii in culture of blood for three times. Despite treatment with amphotericin B and voriconazole, the patient died. The in vitro antifungal susceptibilities of the T. asahii isolates were only available after the patient died. In vitro antifungal susceptibility tests showed high caspofungin and amphotericin B minimal inhibitory concentrations (MICs) value for this Trichosporon strain (MICs, 16 microg/ml, and>32 microg/ml, respectively). Fluconazole, itraconazole, and voriconazole exhibited low MICs in vitro (MICs, 4 microg/ml, 0.5 microg/ml, and

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Diabetes Mellitus, Type 2; Drug Resistance, Multiple, Fungal; Echinocandins; Fatal Outcome; Fungemia; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lipopeptides; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Trichosporon

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Drug Resistance, Fungal; Female; Fever; Fungemia; Humans; Immunocompromised Host; Male; Neutropenia

With its broad spectrum of activity and better tolerability profile than conventional amphotericin B, liposomal amphotericin B (L-AmB) may be the drug of choice for antifungal prophylaxis in haematological patients. An open-label, multicentre, prospective, pilot study was conducted in adult patients receiving chemotherapy for acute leukaemia (AL) or myeloablative allogeneic stem cell transplantation (SCT). Patients received weekly 10mg/kg infusions of L-AmB for 4 weeks for AL and 8 weeks for SCT. The primary objective was safety, with particular attention to infusion-related reactions and nephrotoxicity. Twenty-nine adult patients were included: 21 AL (median age 52 years) and 8 SCT (median age 37 years). The most frequent adverse events (AEs) related to study drug were infusion-related reactions, 12 of which (from a total of 76 infusions) led to increased infusion duration for better tolerance. No AE related to the study drug led to discontinuation of prophylactic treatment in AL patients. In SCT patients, eight AEs (in six patients) reported to be related to study treatment led to treatment discontinuation. Enrolment was discontinued in the SCT group as recommended by the independent data review committee in accordance with the 10% limit of AEs (CTC grade 3-4) fixed by the protocol. The appropriate timing of high-dose prophylactic L-AmB remains to be determined in the SCT setting to optimise the safety profile of this regimen. For AL, a 10mg/kg weekly dose appears to be well tolerated during chemotherapy and may represent an important tool towards improving AL patient outcome.

Topics: Adult; Amphotericin B; Antifungal Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Pilot Projects; Prospective Studies; Safety

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

To describe the clinical presentation, management, and outcomes of patients with Penicillium marneffei infections in a regional hospital in Hong Kong.. Retrospective study.. A regional and tertiary human immunodeficiency virus-referral hospital in Hong Kong.. Those who had penicilliosis during the inclusive period January 1994 to February 2004.. Forty-seven immunocompromised patients (44 being human immunodeficiency virus-positive) with penicilliosis were retrospectively studied. Fever, malaise, and anaemia were the commonest presentations. Most diagnoses were obtained from blood cultures (83%) and lymph node biopsies (34%). Five (11%) died, death being attributable to penicilliosis; four (9%) of them had received no specific antifungal treatment due to late presentation and late diagnosis. The CD4 count of human immunodeficiency virus-infected patients upon diagnosis of penicilliosis was low (median, 20.0 cells/mm3). Most (70%) patients received amphotericin B as an induction treatment, followed by oral itraconazole, although a smaller proportion (21%) received oral itraconazole only. All surviving human immunodeficiency virus-infected patients took highly active antiretroviral treatment and oral itraconazole as secondary prophylaxis after treatment of penicilliosis. The prognosis appeared satisfactory with early diagnosis and administration of appropriate antifungal therapy. Relapse ensued in two (4%) of the patients only.. Penicillium marneffei infection in immunocompromised patients is a serious disease with significant mortality if not diagnosed early and treated with appropriate antifungal drugs. Simple investigations like blood culture enable the diagnosis in the majority of cases. Immunocompromised patients who have been successfully treated should receive oral itraconazole as a maintenance therapy to prevent relapse.

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Dermatomycoses; Diagnosis, Differential; Drug Therapy, Combination; Fungemia; Hong Kong; Humans; Infusions, Intravenous; Itraconazole; Lung Diseases, Fungal; Opportunistic Infections; Penicillium; Retrospective Studies; Survival Rate

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

In vitro susceptibility of 58 isolates of Pichia anomala to five antifungal drugs using two broth microdilution methods (CLSI and EUCAST) was analyzed. Low susceptibility to itraconazole was observed. Fluconazole, voriconazole, amphotericin B, and caspofungin showed good antifungal activity, although relatively high drug concentrations were necessary to inhibit the isolates.

Topics: Amphotericin B; Antifungal Agents; Cross Infection; Fluconazole; Fungemia; Humans; Itraconazole; Microbial Sensitivity Tests; Pichia

Isavuconazole is the active component of the new azole antifungal agent BAL8557, which is entering phase III clinical development. This study was conducted to compare the in vitro activities of isavuconazole and five other antifungal agents against 296 Candida isolates that were recovered consecutively from blood cultures between 1995 and 2004 at a tertiary care university hospital. Microdilution testing was done in accordance with CLSI (formerly NCCLS) guideline M27-A2 in RPMI-1640 MOPS (morpholinepropanesulfonic acid) broth. The antifungal agents tested were amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, and isavuconazole. C. albicans was the most common species, representing 57.1% of all isolates. There was no trend found in favor of non-Candida albicans species over time. In terms of MIC(50)s, isavuconazole was more active (0.004 mg/liter) than amphotericin B (0.5 mg/liter), itraconazole (0.008 mg/liter), voriconazole (0.03 mg/liter), flucytosine (0.125 mg/liter), and fluconazole (8 mg/liter). For isavuconazole, MIC(50)s/MIC(90)s ranged from 000.2/0.004 mg/liter for C. albicans to 0.25/0.5 mg/liter for C. glabrata. Two percent of isolates (C. glabrata and C. krusei) were resistant to fluconazole; C. albicans strains resistant to fluconazole were not detected. There were only two isolates with MICs for isavuconazole that were >0.5 mg/liter: both were C. glabrata isolates, and the MICs were 2 and 4 mg/liter, respectively. In conclusion, isavuconazole is highly active against Candida bloodstream isolates, including fluconazole-resistant strains. It was more active than itraconazole and voriconazole against C. albicans and C. glabrata and appears to be a promising agent against systemic Candida infections.

Topics: Antifungal Agents; Area Under Curve; Candida; Fungemia; Humans; Microbial Sensitivity Tests; Nitriles; Pyridines; Triazoles

Neutropenic mice with latent trichosporonemia were given various antifungal agents (amphotericin B, fluconazole, itraconazole) or saline to determine which antifungal agent could be useful for prophylaxis. The 3-week-survival rate was 80% in the fluconazole group, 50% in the amphotericin B group, 45% in the itraconazole group, and 30% in the saline group. Compared with the other antifungal agents, fluconazole offered superior prophylaxis against the progression of trichosporonosis fungemia to disseminated disease (P<0.05). These results suggest that clinical studies are warranted to investigate fluconazole prophylaxis of trichosporonosis progression in neutropenic patients, such as people receiving chemotherapy and patients who have received solid organ transplants.

Topics: Amphotericin B; Animal Structures; Animals; Antibiotic Prophylaxis; Antifungal Agents; Cyclophosphamide; Disease Models, Animal; Fluconazole; Fungemia; Itraconazole; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Neutropenia; Survival Analysis; Treatment Outcome; Trichosporon

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

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

Primary treatment failure and mortality in non-neutropenic patients with candidemia is high according to clinical trial experience. Current guidelines are mainly useful only for first line treatment strategies.We describe treatment failure and persistent protracted Candida albicans candidemia without clinically evident ocular involvement nor catheter recolonization in a malnourished non-neutropenic surgical patient with peritonitis. Primary antifungal treatment failure with fluconazole and secondary treatment failure with caspofungin occurred in the absence of evident Candida seeding the eye, valvular endocardium, or the intravascular catheter. Switch to liposomal amphotericin B was followed by clinical and microbiological cure. In patients with multiple risk factors for the acquisition of candidemia and life-threatening clinical conditions, the possibility of primary/secondary failure of new potent antifungal regimens may be initially neglected. Additional multicenter controlled clinical data are needed to guide the timing and choice of secondary antifungal treatment regimens in non-neutropenic candidemia patients.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Caspofungin; Drug Combinations; Echinocandins; Female; Fluconazole; Fungemia; Humans; Ileostomy; Lipopeptides; Middle Aged; Peptides, Cyclic; Phosphatidylcholines; Phosphatidylglycerols; Postoperative Complications; Practice Guidelines as Topic

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Candidiasis; Cryptococcosis; Drug Combinations; Fungemia; Humans; Phosphatidylcholines; Phosphatidylglycerols; Viscera

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

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

Increase in cryptococcal infection has been noticed after acquired immunodeficiency syndrome pandemic. Cryptococcus neoformans can be isolated from blood in the process of dissemination to brain. We report a case of cryptococcal fungaemia in a patient whose cerebrospinal fluid was negative for Cryptococcus neoformans. Retrospective analysis revealed human immunodeficiency virus seropositivity of the patient. He was treated with amphotericin B and fluconazole. Antiretroviral therapy was started, however, the patient succumbed to the infection.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Fungemia; HIV Seropositivity; Humans; Male; Meningoencephalitis; Middle Aged

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Fungemia; Hepatitis B, Chronic; Hepatomegaly; Herpes Zoster; Histoplasmosis; Humans; Male; Splenomegaly; Toxoplasmosis; Ultrasonography; Uremia

Yeast strains obtained from blood cultures and catheters from intensive care units (ICU) and hospitalised oncology paediatrics were studied. Yeast were the first cause of catheter colonisation (51/627), and the third cause of bloodstream infection (44/6065). In catheter, the most frequent species were Candida albicans (34%), C. parapsilosis (27.7%) and C. tropicalis (15%). In blood, C. albicans (40.8%), C. parapsilosis (26.6%), C. tropicalis (15%). Malassezia furfur and Malassezia sympodialis were isolated from catheters from ICU patients. All isolates were susceptible to amphotericin B, 88.8% to itraconazole and 91.9% to fluconazole. Candida albicans and C. tropicalis strains resistant to fluconazole and itraconazol were detected. These results reveal a change in the predominant role of C. albicans as cause of candidemia in hospitalised children and the emergence of antifungal resistant species. These variations emphasise the importance of performing a permanent surveillance to observe and assess them.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Argentina; Candida; Catheterization; Child; Child, Preschool; Drug Resistance, Fungal; Fluconazole; Fungemia; Health Surveys; Humans; Incidence; Infant; Intensive Care Units, Pediatric; Itraconazole; Malassezia; Microbial Sensitivity Tests; Species Specificity

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

Kodamaea ohmeri is a yeast that rarely causes human infections. The first case of K. ohmeri fungaemia in a premature neonate is reported; it was successfully treated with liposomal amphotericin B. Biochemical identification of the yeast was performed by Vitek II and API and was confirmed by rRNA gene sequencing. K. ohmeri as a human pathogenic yeast is uncommon to hospitalized neonates and immunocompromised individuals.

Topics: Amphotericin B; Antifungal Agents; Apgar Score; Cross Infection; Female; Fungemia; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Pichia; Respiration, Artificial

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

The incidence of fungal infections is increasing due to immunocompromised states. We report a case of fungaemia due to a rare fungus - Verticillium, in a 6 year old child diagnosed as a case of acute lymphoblastic leukaemia- L1 with high grade fever. The patient was treated with amphotericin B with a good clinical response.

Topics: Amphotericin B; Antifungal Agents; Child; Fungemia; Humans; Immunocompromised Host; Male; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Verticillium

Pichiafabianii, an uncommon yeast species recovered from clinical specimens, was documented as the cause of an infection in a 5-week-old female twin delivered at 25 and 3/7 weeks. She developed respiratory distress syndrome and necrotizing enterocolitis. At the time of the infection, she was febrile, thrombocytopenic, and still was requiring minimal ventilatory support. Blood cultures drawn on two consecutive days were positive for a germ tube negative yeast. Phenotypic methods including carbohydrate fermentations and assimilations (API 20C AUX) did not identify the yeast. Sequencing of D1/D2 domain of the large subunit rDNA was performed in one laboratory and sequencing a subunit of D2 performed in a second laboratory identified the yeast as P. fabianii. The organism was susceptible in vitro to amphotericin B, fluconazole and 5-fluorocytosinc. The patient responded to amphotericin B and removal of her vascular catheter. This case illustrates that there are an increasing number of fungi that may be pathogenic. Phenotypic tests may fail to identify them, emphasizing the need for commercially available, molecular based assays for identification.

Topics: Amphotericin B; Antifungal Agents; DNA, Fungal; Female; Fungemia; Humans; Infant, Newborn; Infant, Premature; Pichia; Sequence Analysis, DNA

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

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

Candida haemulonii(types I and II) is rarely isolated from clinical specimens. We isolated a strain that is phylogenetically close to C. haemulonii from the blood of a Thai patient, and named it C. pseudohaemulonii sp. nov. (CBS 10099T = JCM 12453T = DMST 17134T). The new species and C. haemulonii types I and II were resistant to amphotericin B and azole agents but were susceptible to a 1,3-beta-D-glucan synthetase inhibitor, micafungin, and 5-flucytosine. The species were easily distinguished using an ID32 yeast identification kit. The taxonomic description of C. pseudohaemulonii sp. nov. is presented.

Topics: Amphotericin B; Antifungal Agents; Candida; Drug Resistance, Fungal; Fluconazole; Fungemia; Microbial Sensitivity Tests; Phylogeny

Candida lipolytica has infrequently been identified as a cause of infection and is associated mostly with vascular catheter-related fungaemia. Patients reported in the literature have been successfully treated with catheter removal or amphotericin B treatment. We report 2 infants with C. lipolytica fungaemia unresponsive to catheter removal and amphotericin B therapy and treated successfully with the addition of caspofungin to amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Candida; Caspofungin; Catheters, Indwelling; Cross Infection; Drug Therapy, Combination; Echinocandins; Female; Fungemia; Humans; Infant; Infant, Newborn; Lipopeptides; Male; Peptides, Cyclic

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

Topics: Amphotericin B; Antifungal Agents; Dermatomycoses; Drug Resistance, Fungal; Endophthalmitis; Exophiala; Female; Fungemia; Humans; Itraconazole; Middle Aged; Mycoses; Opportunistic Infections; Osteolysis; Pregnancy; Pregnancy Complications, Infectious; Pyrimidines; Recurrence; Th2 Cells; Triazoles; Voriconazole

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

The incidence and severity of fungal infections in children with malignant diseases treated with intensive chemotherapy or allogeneic hematopoietic cell transplantation on the hematology-oncology department Children's Hospital Salata Medical School University of Zagreb is analyzed. The efficacy of antifungal therapy is presented.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Child; Child, Preschool; Croatia; Deoxycholic Acid; Drug Combinations; Fungemia; Hematopoietic Stem Cell Transplantation; Hospitals, Pediatric; Hospitals, Teaching; Humans; Immunocompromised Host; Infant; Liposomes; Lung Diseases, Fungal; Mycoses; Neoplasms; Postoperative Complications; Retrospective Studies; Treatment Outcome

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

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Child, Preschool; Female; Fungemia; Humans; Immunocompromised Host; Microbial Sensitivity Tests; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

The incidence of invasive fungal infection is increasing especially in the field of transplantation, affecting as many as 50% of bone marrow transplant (BMT) patients with neutropenia and 5-20% of solid-organ transplant (SOT) recipients. Fusarium species are soil saprophytes and plant pathogens. They may cause superficial mycoses or important opportunistic infections in patients with bone marrow suppression and neutropenia, they have been rarely described in solid organ recipients, and up to now there have been no reports of such infection in isolated liver transplanted patients. We describe a case of disseminated Fusarium solani infection with hepatic localization in a liver transplanted patient that resolved with the administration of amphotericin B. Our observation confirms that Fusarium spp. are emerging pathogens that may most frequently affect not only BMT patients and patients with hematological malignancies, but also SOT patients. They may cause both localized and disseminated infection. In conclusion, Fusarium spp. etiology should be considered in the context of infectious diseases following liver transplantation.

Topics: Adult; Amphotericin B; Antifungal Agents; Fungemia; Fusarium; Humans; Liver; Liver Transplantation; Male

Topics: Amphotericin B; Antifungal Agents; Female; Fungemia; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Middle Aged; Mycoses; Pichia

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

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: Amphotericin B; Antifungal Agents; Blood; Caspofungin; Diagnosis, Differential; Echinocandins; Equipment Contamination; False Positive Reactions; Fungemia; Humans; Immunocompromised Host; Lipopeptides; Mycoses; Paecilomyces; Peptides, Cyclic; Pyrimidines; Species Specificity; Triazoles; United Kingdom; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Diagnosis, Differential; Female; Fluconazole; Fungemia; Humans; Jamaica; Paecilomyces

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

Blastoschizomyces capitatus (formerly known as Geotrichum capitatum and Trichosporon capitatum) is a rare, yet an emerging, cause of invasive infections in immunosuppressed patients. Profound and prolonged neutropenia is the crucial predisposing factor for this yeast infection. Blastoschizomyces capitatus was isolated from peripheral blood cultures of a profoundly neutropenic patient with acute myeloid leukemia (M2 FAB). Despite administration of antifungal chemotherapy with liposomal amphotericin B at 4.5 mg kg(-1) daily, the patient succumbed 4 days after initiation of treatment. Infections attributed to B. capitatus have generally a poor prognosis, although the yeast shows in vitro susceptibility to antifungal agents. Low flucytosine, caspofungin acetate, voriconazole and amphotericin B minimum inhibitory concentration values were also recorded with our isolate. The clinical relevance of the in vitro susceptibility testing against the isolate and the current antifungal chemotherapy regimens against B. capitatus systemic infections are discussed.

Topics: Aged; Amphotericin B; Antifungal Agents; Blood; Fatal Outcome; Fungemia; Geotrichosis; Geotrichum; Greece; Humans; Leukemia, Myeloid, Acute; Male; Neutropenia; Sepsis

A 10-year-old patient with known coccidioidomycosis relapsed and had dysrrhythmias and a right atrial mass. Histopathology and culture after surgical removal revealed that this was a vegetative mass infected with Coccidioides spp. We believe that this is the first case of coccidioidal endocarditis to be reported.

Topics: Amphotericin B; Cardiac Surgical Procedures; Child; Coccidioides; Coccidioidomycosis; Combined Modality Therapy; Endocarditis; Follow-Up Studies; Fungemia; Heart Atria; Humans; Male; Risk Assessment; Severity of Illness Index; Treatment Outcome; Ultrasonography

Disseminated Trichosporon infection in neutropenic patients carries a poor prognosis. Clinical evidence on the use of voriconazole for this infection is limited. The authors report a case of Trichosporon asahii fungemia refractory to liposomal amphotericin B treatment in a boy with acute lymphoblastic leukemia, which resolved after the addition of voriconazole. Both voriconazole and amphotericin B exhibited low minimal inhibitory concentrations and minimal fungicidal concentrations, and their combination was indifferent in vitro. The use of voriconazole for the treatment of trichosporonosis in patients with hematologic malignancies deserves further study.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Fungemia; Humans; Male; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Treatment Outcome; Triazoles; Trichosporon; Voriconazole

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

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

We report the first case of Phialemonium obovatum fungemia with subsequent caseating granulomatas in the lung and Crohn disease-like involvement of the gastrointestinal tract in a bone marrow transplant recipient. This phaeoid fungus has been rarely described as an opportunistic infection in immunosuppressed patients. The patient was diagnosed with chronic myelogenous leukemia and underwent subsequent peripheral bone marrow transplant. After 6 months, he developed graft-versus-host disease of the skin and liver with fever and severe diarrhea. Fecal bacterial cultures and cytomegalovirus serologies were negative. Computed tomographic scan showed a peripheral pulmonary mass. A lung wedge biopsy of the lesion showed septate branching hyphae (4-5 microm in diameter) with terminal globular structures (10 microm in diameter). The hyphae were similar in width to that of an Aspergillus species but had a more moniliform appearance. Blood cultures grew a pure culture of P. obovatum. He was treated with amphotericin B and itraconazole for 6 months without remission of the diarrhea. Biopsies of the stomach, colon, and rectum showed granulomatous inflammation with marked crypt distortion simulating Crohn disease. In retrospect, the fungus was found to be resistant to both of the aforementioned drugs and susceptible to voriconazole and posaconazole. The gastrointestinal findings raise the possibility of further dissemination of a partially treated Phialemonium infection.

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Bone Marrow Transplantation; Drug Resistance, Fungal; Fungemia; Gastrointestinal Diseases; Graft vs Host Disease; Granuloma; Humans; Immunocompromised Host; Itraconazole; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lung Diseases, Fungal; Male; Middle Aged; Opportunistic Infections; Pyrimidines; Triazoles; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Catheterization, Central Venous; Catheters, Indwelling; Fungemia; Humans; Infant; Liposomes

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

Topics: Acute Kidney Injury; Adult; Amphotericin B; Aspergillosis; Aspergillus niger; Female; Follow-Up Studies; Fungemia; Humans; Injections, Intralesional; Kidney Diseases; Kidney Tubules, Collecting; Radiography; Risk Assessment; Treatment Outcome; Ureter

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

An allogeneic stem cell transplant recipient developed pulmonary infiltrates and Aspergillus antigenemia during prophylactic low-dose liposomal amphotericin B. No response to therapy was observed after increasing the dose of liposomal amphotericin B and addition of caspofungin, and breakthrough candidemia developed. Therapy switch to voriconazole did not prevent the development of lethal septic shock. Shortly before death, Scopulariopsis brevicaulis was cultured from bronchial secretions, and positive blood cultures demonstrated persistent candidemia due to Debaryomyces hansenii, teleomorph of Candida famata.

Topics: Aged; Amphotericin B; Anemia, Aplastic; Ascomycota; Aspergillosis; Body Fluids; Caspofungin; Drug Therapy, Combination; Echinocandins; Fatal Outcome; Fungemia; Hematopoietic Stem Cell Transplantation; Humans; Lipopeptides; Male; Mycoses; Peptides, Cyclic; Pyrimidines; Saccharomycetales; Shock, Septic; Triazoles; Voriconazole

Paecilomyces variotii, an emerging hyalohyphomycetes, has been reported to be susceptible in vitro to voriconazole. We describe a case of disseminated P. variotii infection in a neutropenic child with relapsed leukaemia who was on voriconazole prophylaxis. The P. variotii isolate was resistant to voriconazole in vitro. The patient responded to liposomal amphotericin B.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Dermatomycoses; Drug Resistance, Fungal; Fungemia; Humans; Lung Diseases, Fungal; Male; Microbial Sensitivity Tests; Mycoses; Neutropenia; Paecilomyces; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Radiography; Treatment Outcome; Triazoles; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Biopsy, Needle; Coccidioidomycosis; Dermatomycoses; Diagnosis, Differential; Female; Follow-Up Studies; Fungemia; Humans; Immunohistochemistry; Middle Aged; Mycosis Fungoides; Risk Assessment; Severity of Illness Index; Skin Neoplasms; Treatment Outcome

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

Topics: Amphotericin B; Antifungal Agents; Catheterization, Central Venous; Female; Fungemia; Humans; Infant, Newborn; Mycoses; Saccharomyces cerevisiae

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

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

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

The clinical relevance of mold isolated from blood cultures, even in severely immunosuppressed allogeneic hematopoietic stem cell transplantation (HSCT) recipients, remains uncertain. The authors hypothesized that isolation of non-Candida fungi from blood cultures in patients undergoing high-risk HSCT would have clinical significance.. The authors reviewed the records of 73 allogeneic HSCT recipients between January 1, 1993 and January 1, 2001 in whom fungal species were isolated from blood cultures.. Fifty-two episodes of non-Candida fungemia occurred in 48 patients (66%) after a median of 10 days (range, 2-341) after transplantation. All 48 patients had indwelling intravascular catheters, and 23 patients (48%) had profound neutropenia. Thirty-five of 48 patients had received partially matched, related donor stem cell grafts (19 patients had 3-antigen-mismatched grafts); 35 patients had undergone T-cell depleted transplantation and 9 patients were receiving treatment for acute graft-versus-host disease. In 5 of 48 patients (10%), death was attributed to fungemia that occurred 8-11 days after the initial fungal blood culture was obtained; all 5 patients were age > 30 years. No deaths occurred in the younger age group (n = 22 patients; P = 0.05). In the 24 patients who did not receive systemic antifungal therapy, 4 deaths (17%) were attributed to infections with Penicillium (n = 2 patients), Epicoccum (n = 1 patient), or Penicillium plus Cladosporium species (n = 1 patient). Of the 24 patients who received amphotericin B, only 1 patient (4%) died as a result of a probable hematogenous Aspergillus species infection; this difference in outcome, however, was not significant (P = 0.2).. Most of the non-Candida fungal blood culture isolates in recipients of high-risk, mismatched donor transplantation were clinically nonsignificant. However, because these low-virulence saprophytes occasionally may cause life-threatening disease, a reevaluation of the existing diagnostic paradigm is needed so that clinically significant fungemia may be differentiated from pseudofungemia.

Topics: Adolescent; Adult; Amphotericin B; Aspergillus; Child; Child, Preschool; Cladosporium; Culture Techniques; Female; Fungemia; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Lymphoma; Male; Middle Aged; Penicillium; Retrospective Studies; Risk Factors; Transplantation, Homologous; Treatment Outcome

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; Candida; Candidiasis; Fungemia; Humans; Pyrimidines; Randomized Controlled Trials as Topic; Treatment Outcome; Triazoles; Voriconazole

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

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

In this report, a case of Fusarium fungaemia developed in an acute lymphoblastic leukemia (ALL) patient was presented. A seven year old girl who had weakness, loss of appetite, paleness and ecchymosis on legs applied to Pediatric Hematology Service and cytotoxic chemotherapy was started after she had been diagnosed as ALL-L1. Her chemotherapy was stopped because of increase in fever, leukopenia and neutropenia. Central venous catheter and peripheral blood cultures were obtained. Fusarium thapsinum was recovered from blood cultures, obtained in two consecutive days. Thereupon central venous catheter of the patient was removed and intravenous amphotericin B was added to the therapy. On the fifth day of febrile neutropenia attack, her fever was decreased after the onset of antifungal therapy. Radiological examinations were normal and no fungal growth was observed in the later blood cultures. On the 21st day of amphotericin B therapy, chemotherapy was started again and amphotericin B was changed to peroral itraconazole (200 mg/day) at the fifth week. The patient whose itraconazole therapy was stopped after three months, was still in remission and continued receiving her prolonged therapy. In conclusion, Fusarium infections which manifest with fungaemia and fever as the only symptoms, should be taken into consideration in neutropenic patients receiving immunosuppressive therapy.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Catheterization, Central Venous; Catheters, Indwelling; Child; Female; Fever; Fungemia; Fusarium; Humans; Immunosuppressive Agents; Itraconazole; Leukopenia; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

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

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

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

We report a case of fungemia caused by the yeast-form fungus Pichia ohmeriin a 59-year-old hospitalized patient. P. ohmeri was found in all of the patient's blood cultures collected on days 52, 57, 59, and 64 of his hospital stay. Intermittent fever developed on the 52nd hospital day and persisted for about 10 days. The patient had previously received intensive antimicrobial therapy for a ventriculoperitoneal shunt infection and subsequent nosocomial pneumonia. Although a central venous catheter was not used in the patient, he suffered from tender swelling of the right leg due to peripheral phlebitis at the site of insertion of a peripheral venous catheter (which had already been removed at the onset of fever), the same site from which P. ohmeri was isolated. The fungemia and phlebitis cleared following 14-day amphotericin B therapy. This case shows that P. ohmeri can be a nosocomial bloodstream pathogen associated with phlebitis.

Topics: Amphotericin B; Antifungal Agents; Cross Infection; Fungemia; Humans; Male; Middle Aged; Mycoses; Phlebitis; Pichia

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

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

A 12-year-old immunocompromised boy was hospitalized because of invasive aspergillosis with lung and central nervous system involvement. He was treated with surgery and liposomal amphotericin B, but he developed a pulmonary empyema and a bronchopleural-cutaneous fistula. A catheter was placed through the fistula, and amphotericin B (up to 50 mg in 10 ml of 5% dextrose) was instilled daily into the pleural cavity for 45 days. Treatment was well-tolerated, and the empyema resolved completely, with no evidence of recurrence after 2 years of follow-up.

Topics: Amphotericin B; Aspergillosis; Child; Empyema, Pleural; Follow-Up Studies; Fungemia; Humans; Immunocompromised Host; Infusions, Intravenous; Injections, Intralesional; Magnetic Resonance Imaging; Male; Risk Assessment; Tomography, X-Ray Computed; Treatment Outcome

Ina 24-month-old girl with acute lymphoblastic leukemia and invasive aspergillosis, only combination therapy with liposomal amphotericin B and caspofungin achieved a good response. Combination therapy could be a useful treatment option in children with invasive fungal disease, but before it can be routinely recommended, carefully controlled in vivo studies and well-designed randomized clinical trials are needed.

Topics: Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Caspofungin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Echinocandins; Female; Follow-Up Studies; Fungemia; Humans; Infant; Lipopeptides; Liposomes; Opportunistic Infections; Peptides; Peptides, Cyclic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Assessment; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome

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

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

Trichosporon asahii (T. asahii) is an uncommon cause of yeast infection in preterms. We present a 27-week gestational age female with clinical evidence of sepsis, such as patchy infiltrations on chest roentgenogram, and yeast growing in urine and blood cultures. Conventional amphotericin B was empirically added in a dose of 0.5 mg/kg, q8h to standard protocol of the neonatal intensive care unit. Dose of the drug was induced to 1 mg/kg because the patient had not improved when the organism was identified as T. asahii on the pretreatment urine and blood cultures. Both cultures were clear on the 10th day of amphotericin B therapy and treatment was ceased on the 21st day. The patient was healthy when discharged. Trichosporon infections in neonates have been almost uniformly fatal. Most strains of T. asahii may be confused with Candida spp. on initial culture examinations. Therefore, delays in appropriate treatment may occur.

Topics: Adult; Amphotericin B; Antifungal Agents; Diagnosis, Differential; Female; Fungemia; Humans; Infant, Newborn; Infant, Premature; Pregnancy; Respiration, Artificial; Surface-Active Agents; Trichosporon

We report two cases of Acremonium fungemia with proven involvement of the skin and probably of the lung in patients who were both undergoing chemotherapy, one for mantle cell lymphoma and the other for acute lymphoblastic leukemia. Both patients failed amphotericin B deoxycholate treatment and were successfully treated with voriconazole with very mild toxicity.

Topics: Acremonium; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Female; Fungemia; Humans; Lymphoma, Mantle-Cell; Middle Aged; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Triazoles; Voriconazole

This study evaluated the value of polymerase chain reaction (PCR) for diagnosing and monitoring of invasive aspergillosis during amphotericin B therapy. PCR, microscopy and culture of tissues samples (n = 126) and blood samples (n = 78) of experimentally infected mice (n = 42) were performed. The PCR results of treated were compared to those of untreated animals; Aspergillus fumigatus and A. terreus were used in this study. In the amphotericin B treated group the sensitivities of PCR, microscopic examination and culture of the various tissues were 69, 58, and 53%, respectively; the specificities of all examinations were 100%. In the untreated group the sensitivities of PCR, microscopic examination, and culture were 72, 64, and 57%, respectively; the specificities of all examinations were 100%. The 78 blood samples taken from mice under therapy were tested by PCR over a period of 8 days following Aspergillus infection. The test sensitivity was 77%, the specificity 46%, the positive predictive value 59%, and the negative predictive value 67%. In the untreated group the sensitivity was 92%, the specificity 46%, the positive predictive value 63%, and the negative predictive value 86%. The results suggest that this PCR method has possible clinical value for improving the diagnosis of invasive Aspergillus infection. Monitoring of blood under antifungal therapy is not recommended.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Disease Models, Animal; DNA, Fungal; Female; Fungemia; Mice; Mice, Inbred BALB C; Polymerase Chain Reaction; Reference Values; Sensitivity and Specificity

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candida; Candidiasis; Caspofungin; Echinocandins; Fungemia; Humans; Lipopeptides; Peptides; Peptides, Cyclic

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis, Cutaneous; Catheterization, Central Venous; Drug Combinations; Fungemia; Humans; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols; Treatment Outcome

Candida glabrata is an increasing cause of candidemia, especially at cancer and bone marrow transplant centers where fluconazole is used for antifungal prophylaxis. This yeast is less susceptible to fluconazole in vitro than is Candida albicans. We compared the characteristics of patients who had C. glabrata and C. albicans candidemia at a large cancer center.. We searched the microbiological laboratory reports and identified 116 cases of C. glabrata candidemia between 1993 and 1999. The 116 cases of C. albicans candidemia that occurred most closely in time (before or after each case of C. glabrata candidemia) served as the control group. Data were collected from patients' medical records.. When compared with patients who had C. albicans infection, patients with C. glabrata candidemia more often had an underlying hematologic malignancy (68 [59%] vs. 26 [22%], P = 0.0001), had an Acute Physiology and Chronic Health Evaluation (APACHE) II score > or =16 (55 [48%] vs. 28 [25%], P = 0.0002), and received fluconazole prophylaxis (57 [49%] vs. 8 [7%], P = 0.0001). Patients with C. albicans candidemia more often had concomitant infections (101 [87%] vs. 78 [67%], P = 0.0003) and septic thrombophlebitis (11 [10%] vs. 2 [2%], P = 0.01). Among patients treated with antifungal therapy, those with C. albicans candidemia had a significantly greater overall response to therapy (83/104 [80%] vs. 60/97 [62%], P = 0.005) and to primary therapy (74/104 [71%] vs. 45/97 [46%], P = 0.0003). Amphotericin B preparations were not more effective than fluconazole (19/45 [42%] vs. 20/38 [53%], P = 0.5) in patients with C. glabrata candidemia. Fluconazole was less effective against C. glabrata than against C. albicans (20/38 [53%] vs. 57/74 [77%], P = 0.008).. C. glabrata has emerged as an important cause of candidemia, especially among neutropenic patients who receive fluconazole prophylaxis.

Topics: Amphotericin B; Antifungal Agents; APACHE; Bone Marrow Transplantation; Candida albicans; Candidiasis; Case-Control Studies; Female; Fluconazole; Fungemia; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Postoperative Complications; Regression Analysis; Treatment Outcome

In order to assess the risk factors for breakthrough candidemia (candidemia occurring in patients receiving at least 3 days of systemic fluconazole or amphotericin B), 270 cases of candidemia occurring in two tertiary hospitals were analyzed. Using multivariate analysis, profound neutropenia (<100/mm(3)) (odds ratio [OR], 9.14), use of corticosteroids (OR, 3.17), and heavy antibiotic exposure (previous use of 2 or more antibiotics for at least 14 days) (OR, 2.93) were identified as risk factors. Neither the susceptibility of the isolates nor the presence of a catheter was found to be a risk factor. These data suggest that gastrointestinal colonization plays a major role in the development of breakthrough candidemia.

Topics: Amphotericin B; Anti-Bacterial Agents; Candidiasis; Fluconazole; Fungemia; Humans; Multivariate Analysis; Neoplasms; Neutropenia; Odds Ratio; Retrospective Studies; Risk Factors

With the increased use of indwelling central venous catheters, increasing numbers of cases of Rhodotorula fungemia have been observed in patients with neoplasia and neutropenia. In most patients with catheter-related Rhodotorula fungemia, the condition has been treated with broadspectrum antibiotics. We report two cases of central venous catheter-related Rhodotorula rubra fungemia that occurred in patients with acute myeloblastic leukemia. Both patients were in a state of neutropenia. One patient was treated with amphotericin B and his central venous catheter was removed, but he died of Klebsiella pneumoniae bacteremia. The other patient was treated with amphotericin B and discharged, with a central venous catheter, after recovery from neutropenia. Although the management of catheter-related Rhodotorula fungemia infections remains controversial, resolution of the underlying disease is more important than catheter removal for recovery from Rhodotorula rubra fungemia.

Topics: Adolescent; Amphotericin B; Catheterization, Central Venous; Female; Fungemia; Humans; Male; Middle Aged; Rhodotorula

It is not uncommon to see amphotericin B treatment failure in patients with systemic infection caused by Candida lusitaniae. We report a patient with stage IV ovarian carcinoma and C. lusitaniae sepsis whose treatment with amphotericin B failed. The initial blood isolate was susceptible to amphotericin B in vitro; however, the MIC for a blood isolate recovered 7 weeks after treatment began showed a fourfold increase. Direct subculture of two positive blood samples obtained within a week of the patient's death showed the coexistence of two distinct colony color variants on CHROMagar Candida (CAC). One variant was susceptible to amphotericin B, and one was resistant. These results emphasize the importance of repeat amphotericin B susceptibility testing for patients with persistent C. lusitaniae infection. The presence of colony variants on CAC may signal the emergence of amphotericin B resistance in C. lusitaniae and should be investigated.

Topics: Aged; Amphotericin B; Antifungal Agents; Blood; Candida; Candidiasis; Chromogenic Compounds; Culture Media; Drug Resistance, Fungal; Electrophoresis, Gel, Pulsed-Field; Fatal Outcome; Female; Fungemia; Humans; Microbial Sensitivity Tests; Treatment Failure

Demographic information, risk factors, therapy, and outcome for all patients who had candidemia at King Fahad teaching hospital Al-khobar, between January 1995 and January 2000 were retrospectively reviewed. Thirty-two candidemic patients were identified. Candida parapsilosis was the most frequently isolated species (44%), followed by Candida tropicalis (25%), Candida albicans (19%), Candida krusei (6%), Candida glabrata (3%), and Candida guilliermondi (3%). Risk factors included recent broad-spectrum antibiotics use (100%), ICU residency (71%), central venous catheters (66%), recent surgery (56%), total parenteral nutrition (43%), and immunosuppressive therapy (31%). Fluconazole was used before the onset of candidemia in only two patients. The overall mortality rate was 44%. Eight (25%) episodes of candidemia were not diagnosed and treated before the patient's demise. In view of the high mortality rate associated with hematogenous candidiasis, and lack of sensitive and specific laboratory tests necessary for the premortem diagnosis of infection, empirical antifungal therapy is recommended for high-risk patients.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; Female; Fluconazole; Fungemia; Hospital Bed Capacity, 300 to 499; Hospitals; Humans; Infant, Newborn; Male; Middle Aged; Risk Factors; Saudi Arabia

A bloodstream infection due to Candida haemulonii afflicting a patient with fever and a medical history of megaloblastic anemia is reported. The clinical isolate was misidentified by the API 20C and VITEK identification systems. The results of susceptibility tests showed that the MIC of amphotericin B for C. haemulonii was 4 microg/ml. Additional susceptibility testing procedures based on the use of antibiotic medium 3 and Iso-Sensitest broth were performed, and killing curves were determined. Two collection strains of C. haemulonii were employed as controls. The three isolates exhibited resistance to amphotericin B in vitro regardless of the antifungal susceptibility testing method employed. In addition, the MICs of fluconazole for the three isolates were high. Further studies are needed in order to ascertain whether this species exhibits innate or acquired resistance to amphotericin B and other antifungal agents.

Topics: Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Fungemia; Humans; Male; Microbial Sensitivity Tests; Mycological Typing Techniques

The present study was conducted over a period of 6 months to determine the Candida species causing candidemia in a neonatal intensive care unit and to analyse the risk factors associated with acquisition of significant fungemia. Speciation of the 19 isolated Candida spp was done by the standard techniques. Antimicrobial susceptibility of these isolates was determined by disc diffusion method against Amphotericin B, Fluconazole, Ketoconozole and 5-Flucytosine. Candida glabrata was the most common species involved (42.1%). Other species isolated were C. tropicalis (31.6%). Calbicans (21.1%) and C.parapsilosis (5.2%). All the isolates were sensitive to Amphotericin B. Resistance to other antigungal agents was seen only in C. globrata. Significant candidemia was seen in 14/19 (72.6%) of neonates. Risk factors found to be associated with significant candidemis in these neonates included intake of multiple broad-spectrum antibiotics (p<0.0001), use of total parenteral nutrition (p<0.045) and ventilators (p<0.0001).

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; Fungemia; Hospitals; Humans; Incidence; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Risk Factors

Fungi have become increasingly important causes of nosocomial bloodstream infections. The major cause of nosocomial fungemia has been Candida spp, but increasingly molds and other yeasts have caused disease. Exophiala jeanselmei and members of the genus Rhinocladiella are dematiaceous moulds, which have been infrequently associated with systemic infection and have not been described as causes of fungemia. In this paper, the occurrence of 23 cases of fungemia due to these organisms over a 10-month period is reported and the clinical characteristics of patients and outcomes are described. The majority of patients were immunosuppressed; 21 of 23 (91%) had received blood products and 78% had a central venous catheter. All patients had at least one manifestation of fever, but only one patient had signs or symptoms suggesting deep-seated infection. Antifungal therapy was given to 19 of the 23 patients; of those who did not receive therapy, 3 died prior to the culture result and 1 had been discharged without therapy. Antifungal susceptibility of the organisms showed activity of amphotericin B, itraconazole, and the new triazole antifungals voriconazole and posaconazole. E. jeanselmei and Rhinocladiella species are potential causes of nosocomial fungemia and may be associated with systemic infection.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Ascomycota; Catheterization, Central Venous; Child; Cross Infection; Female; Fungemia; Humans; Incidence; Male; Middle Aged; Mycoses; Treatment Outcome

Candida lusitaniae is an infrequent cause of fungemia. We identified 12 cases of C. lusitaniae fungemia that occurred at the University of Texas M. D. Anderson Cancer Center from 1988 to 1999. The mean age of patients was 48 years (range 20--70 years). Eight patients had hematologic malignancy or had received a bone marrow transplant, and 4 had a solid tumor. Most patients (75%) were neutropenic (<10(3)/mm(3)). Treatment with amphotericin B alone failed for 3 of 6 patients, irrespective of neutropenic status. Fluconazole was effective as a single agent in 3 patients with solid tumors. The combination of amphotericin B plus fluconazole was effective treatment for two-thirds of patients with hematologic malignancy, despite persistence of neutropenia. The mortality rate associated with C. lusitaniae infection was 25%. C. lusitaniae presents as breakthrough fungemia in immunocompromised patients and is associated with failure of amphotericin B therapy. Fluconazole may be a useful agent in the treatment of this infection.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Candida; Candidiasis; Drug Therapy, Combination; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasms; Neutropenia; Treatment Failure

We assessed the distribution, antifungal susceptibility, and treatment associated with 161 non-Candida albicans isolates recovered from hospitalized patients over a 6-month period. The three most prevalent species were C. glabrata (100), C. tropicalis (28), and C. krusei (15). Resistance of C. glabrata to fluconazole and itraconazole were 6% and 17% respectively; 80% of the fluconazole-resistant isolates were cross-resistant to itraconazole. Prior azole exposure significantly reduced azole susceptibility in C. glabrata and also affected its subsequent selection among colonized patients. Only 21% of the patients had clinical infections. Patients with fungemia were more likely to be treated with amphotericin versus an azole. Overall treatment success was higher in patients treated with amphotericin versus an azole (56% vs 31%). Routine susceptibility testing on all Candida species does not appear necessary except where therapy with an azole is being considered to detect resistant isolates or for epidemiologic surveillance purposes. Further studies are needed to delineate the relationship between azole MICs and treatment outcomes of invasive candidiasis due to non-C. albicans species.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candidiasis; Drug Resistance, Microbial; Fluconazole; Fungemia; Humans; Itraconazole; Microbial Sensitivity Tests; Prospective Studies; Treatment Outcome

Candida parapsilosis is an increasingly important bloodstream pathogen in neonatal intensive care units (NICU). We investigated a cluster of bloodstream infections in a NICU to determine whether nosocomial transmission occurred. During a 3-day period, 3 premature infants hospitalized in the same unit presented with sepsis caused by C. parapsilosis. Electrophoretic karyotype of the organisms was performed by using pulsed field gel electrophoresis in a countour-clamped homogeneous electric field system. The isolate from 1 newborn could not be typed, and the isolates from the remaining 2 infants had identical patterns. All 3 cases are described. We conclude that nosocomial transmission of C. parapsilosis occurred and that neonates under intensive care may represent a risk group for this pathogen.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; Diseases in Twins; Electrophoresis, Gel, Pulsed-Field; Fungemia; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intensive Care Units, Neonatal; Karyotyping; Risk Factors

Topics: Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candidiasis; Cross Infection; Female; Fluconazole; Flucytosine; Fungemia; Humans; Male; Postoperative Complications; Risk Factors; Slovakia; Survival Rate

The aim of the present study was to evaluate the diagnostic significance of the D-arabinitol/L-arabinitol ratio in urine of neutropenic patients with suspected fungal infection. D-arabinitol/L-arabinitol ratios were determined in 373 serial urine samples of 104 patients with haematological malignancies receiving empirical amphotericin B treatment for suspected invasive fungal infection. Twenty-eight (8%) urine samples obtained from 17 (16%) patients were positive (ratio > or =4). Eight (47%) patients had positive urine samples at the initiation of empirical amphotericin B treatment and the rest from 7 to 30 days after empirical therapy was started. Several urine samples were positive in six patients. Only one of the five patients with candidemia had elevated D-arabinitol/L-arabinitol ratios (persistent Candida krusei fungaemia). Four patients with transient candidemia and seven patients with invasive mould infections were negative. Patients who died during the study period had significantly higher D-arabinitol/L-arabinitol ratios than patients who survived (P=0.0002). Pneumonia was the most common manifestation of infection (53% of patients with elevated D-arabinitol/L-arabinitol ratios) and was associated with an especially high mortality (67%). The present study shows that elevated urine D-arabinitol/L-arabinitol ratios are common in febrile, neutropenic patients. However, the urine arabinitol test did not detect transient candidemia at elevated levels during the course of infection. Furthermore, D-arabinitol/L-arabinitol ratios were often elevated in the late phase of infection only. This contests the use of this test in guiding the initiation of antifungal therapy. The detection of elevated arabinitol levels in neutropenic patients during empirical amphotericin B treatment is associated with poor prognosis.

Topics: Adult; Aged; Amphotericin B; Antiviral Agents; Candida; Candidiasis; Female; Fungemia; Humans; Male; Middle Aged; Neutropenia; Sugar Alcohols

Recently, the methodology that will serve as a basis of the standard for antifungal susceptibility testing of fermentative yeasts of the European Committee on Antibiotic Susceptibility Testing has been described. This procedure employs a spectrophotometric method for both inoculum adjustment and endpoint determination. However, the utilization of a spectrophotometer requires studies for standardization. The present work analyzes the following parameters: (i) accuracy of inoculum preparation, (ii) correlation between optical density and CFU per milliliter, (iii) influence of the wavelength on the endpoint determination, and (iv) influence of the dimethyl sulfoxide concentration on the growth kinetics. The main results can be summarized as follows: (i) inoculum preparation following the methodology recommended by the National Committee for Clinical Laboratory Standards is an exact procedure; (ii) the relationship between optical density and CFU per milliliter is linear (coefficient of determination, r(2) = 0.84); (iii) MICs obtained by means of spectrophotometric readings at different wavelengths are identical (for amphotericin B, an intraclass correlation coefficient of 0.98 was obtained; for fluconazole, the intraclass correlation coefficient was 1); and (iv) a 2% concentration of dimethyl sulfoxide produces a significantly slower and lower growth curve of Candida spp. than other concentrations.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Colony Count, Microbial; Dimethyl Sulfoxide; Fluconazole; Fungemia; Humans; Microbial Sensitivity Tests; Spectrophotometry

The aim of this study was to review the characteristics and outcome of 21 patients with invasive mucormycosis treated with amphotericin B colloidal dispersion (ABCD) in five phase I and phase II studies. Mucormycosis is an increasing concern in immunocompromised patients, in whom mortality exceeds 60%. The standard treatment has been amphotericin B combined with surgical debridement. Twenty-one patients with invasive mucormycosis treated with ABCD, a lipid complex of amphotericin B and cholesteryl sulfate, were identified. Patients were given ABCD on the basis of pre-existing renal insufficiency, development of nephrotoxicity during amphotericin B therapy, or fungal infection that failed to respond to amphotericin B. Response could be evaluated in 20 patients, all of whom had bone marrow or organ transplantation, haematologic malignancies, or diabetes. Infection was disseminated in six patients and localised to the sinuses, lower respiratory tract, or skin in the other patients. ABCD was given at a mean dose of 4.8 mg/kg per infusion for a mean duration of 37 days. Twelve of 20 patients responded to ABCD therapy. Response rates were similar when patients were treated with ABCD alone (4/7) and ABCD combined with surgery (8/13), with more complete response obtained in the latter group. No difference in response rate was observed in leukaemic patients (3/5) or transplant recipients (6/10) compared to diabetics (3/5). No renal or hepatic toxicity was observed. These results compare favourably with the results of standard treatment and suggest that ABCD combined with surgery may be a useful therapy in patients with mucormycosis.

Topics: Adolescent; Adult; Aged; Amphotericin B; Child; Child, Preschool; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Female; Follow-Up Studies; Fungemia; Humans; Infusions, Intravenous; Male; Middle Aged; Mucormycosis; Severity of Illness Index; Survival Rate; Treatment Outcome

The effects of emulsome nanosize range lipid particles containing amphotericin B (EAmB) were compared with the reference formulation containing deoxycholate (Fungizone; Bristol-Myers Squibb, Munich, Germany) and with the commercial amphotericin lipid complex preparation (AmBisome; Nexstar, San Dimas, CA, USA). The minimal inhibitory concentrations of Fungizone and EAmB were identical although killing of Candida albicans was delayed when EAmB was used. In a tissue culture model and in mice, the incorporation of AmB into emulsomes resulted in a considerable reduction of toxicity in comparison with Fungizone. For comparison of the in vivo effect of the preparations a mouse model of systemic infection with C. albicans was used. All preparations were able to reduce the fungal burden in the liver and kidneys in comparison with control animals treated with isotonic saline. AmBisome was more efficient in the reduction of the fungal burden of the liver than EAmB and Fungizone, even when applied in a similar dosage of 1 mg kg(-1). In the kidneys, EAmB and Fungizone was slightly more effective than AmBisome. Therefore, in our models, the incorporation of AmB into nanosize particles was able to reduce toxicity without loss of efficiency. EAmB may be considered a candidate preparation for the treatment of infections with C. albicans in humans.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candidiasis; Cell Culture Techniques; Female; Fungemia; Interleukins; Lipids; Liposomes; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Suspensions; Tissue Distribution

The incidence of disseminated infection with Scedosporium species is increasing in patients with haematological malignancy. Two fatal cases are reported of patients with acute myeloid leukaemia and neutropenia who presented with Scedosporium endophthalmitis. Diagnosis of fungal infection was delayed as blood and vitreous cultures were positive only after 3 days in patient 1 and blood culture was positive at 7 days in patient 2. Despite antifungal therapy with amphotericin B and additional fluconazole in patient 2, both patients died of overwhelming fungal septicaemia. Post-mortem examination of the right globe in patient 1 showed haemorrhagic necrotizing chorioretinitis with numerous fungal hyphae in choroidal vessels, choroid, retina and vitreous. Scedosporium species are often resistant to conventional antifungal therapy including amphotericin B. Diagnosis is difficult and mortality in disseminated infection is high.

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Endophthalmitis; Eye Infections, Fungal; Fatal Outcome; Female; Fluconazole; Fungemia; Humans; Leukemia, Myeloid; Male; Middle Aged; Mycetoma; Neutropenia; Scedosporium

The first case of a cutaneous cryptococcosis associated with systemic erythematous lupus (SLE) diagnosed in our Mycology Reference Centre is presented: a 24-year-old female patient diagnosed with SLE, nephrotic syndrome, arterial hypertension, renal insufficiency due to glomerulonephritis type IV and cellulitis in the right thigh and gluteus. Cryptococcus neoformans was isolated by cutaneous biopsy and haemoculture. Cryptococcal antigen was detected in serum by the latex agglutination test. As the patient did not respond to fluconazol intravenous treatment, amphotericin B administration was performed. She died of acute renal insufficiency.

Topics: Adult; Agglutination Tests; Amphotericin B; Antifungal Agents; Antigens, Fungal; Cellulitis; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Fatal Outcome; Female; Fluconazole; Fungemia; Humans; Injections, Intravenous; Lupus Erythematosus, Systemic; Renal Insufficiency

The fungus Fusarium sacchari was isolated repeatedly from the blood of an immunosuppressed host. The infection was treated successfully with a small dose of amphotericin B. The strain was resistant to this antifungal in vitro. MICs and minimum fungicidal concentrations of six antifungals for the clinical isolate are provided. To our knowledge, this is the first report involving this fungus in a case of fungemia.

Topics: Adult; Amphotericin B; Fungemia; Fusarium; Humans; Immunosuppression Therapy; Kidney Transplantation; Male; Microbial Sensitivity Tests

We compared the efficacies of amphotericin B and voriconazole against invasive pulmonary aspergillosis in a guinea-pig model. A susceptible isolate of Aspergillus fumigatus was used to produce the infection. Voriconazole-treated animals had significantly better survival and decreased fungal burden in the lungs as compared with controls. Although no statistical difference was seen between the efficacies of voriconazole and amphotericin B, a trend favouring voriconazole was noted. Thus, voriconazole, with its cidal activity, may be an attractive alternative to potentially toxic amphotericin B in the treatment of invasive pulmonary aspergillosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Disease Models, Animal; Female; Fungemia; Guinea Pigs; Humans; Lung Diseases, Fungal; Microbial Sensitivity Tests; Pyrimidines; Triazoles; Voriconazole

Candida spp. are the fourth leading cause of bloodstream infection. While the literature on neonatal candidemia is abundant, its prevalence in pediatric surgery cases is hardly mentioned. This study was carried out over a 5-year period to evaluate the prevalence of candidemia in pediatric surgery intensive care unit patients (ICU), and to examine both the neonatal and hospital risk factors for developing candidemia in comparison to control groups of patients with either no infection or with bacteremia, type and outcome of therapy. A total of 1,359 pediatric surgery patients admitted to the ICU and high dependency unit (HDU) were included in the study. Using relevant specimens from them, a microbiological survey was carried out on admission and weekly thereafter. Twenty-five patients developed candidemia during the study period. Twenty-one of them were admitted to ICU. Nine were low birth weight and immature neonates. All 25 patients had underlying disease, most involving the gastroentestinal tract and requiring surgical intervention. All patients had been given broad-spectrum beta-lactam antibiotics with or without aminoglycosides and an anti-anaerobic drug prior to candidemia. The data show that patients who were not infected had very few risk factors that could predispose to candidemia. The bacteremic group of patients had more risk factors: mainly ICU stay, prior antibiotic therapy or GI surgery. The candidemia patients outnumbered these two groups in both neonatal and hospital risk factors. Twenty-three candidemia patients had received amphotericin B and 2 had fluconazole. Seventeen of them improved and the rest expired during therapy. Fourteen of the Candida isolated were C. albicans while the rest belonged to other Candida spp. dominated by C. parapsilosis. In conclusion, candidemia was infrequent in pediatric surgery patients. ICU stay, GI surgery and prior broad-spectrum antibiotic therapy were important risk factors.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Fungemia; Humans; Intensive Care Units, Pediatric; Postoperative Complications; Prevalence; Risk Factors

Candida krusei is inherently resistant to fluconazole and is emerging as a frequent cause of fungemia in patients with hematologic malignant neoplasms.. To determine the risk and prognostic factors associated with C krusei fungemia in comparison with Candida albicans fungemia in patients with cancer.. Retrospective study of 57 cases of C krusei fungemia occurring at the M. D. Anderson Cancer Center, Houston, Tex, from 1989 to 1996. The C krusei cases were compared with 57 cases of C albicans fungemia with respect to demographics, underlying cancer, Acute Physiology and Chronic Health Evaluation II score, immunosuppression status, chemotherapy, and the use of central venous catheters, as well as fluconazole prophylaxis.. At our institution, C krusei accounted for 5% of fungemias during 1989 through 1992 and for 10% during 1993 through 1996. Patients with C krusei fungemia more often had leukemia than patients with C albicans (77% vs 11%; P =.02), whereas catheter-related infections were more common among patients with C albicans fungemia (42% vs 0%; P<.001). Patients with C krusei fungemia had a lower response rate (51% vs 69%; P =.05), largely because they more frequently were neutropenic and had disseminated infection. Mortality related to fungemia was 49% in the cases with C krusei vs 28% in C albicans. Multiple logistic regression analysis showed that persistent neutropenia (P =.02) and septic shock (P =.002) were predictors of poor prognosis.. In neutropenic patients, C krusei fungemia is associated with high mortality. It should be suspected in patients with leukemia who are receiving fluconazole prophylaxis and should be treated aggressively with an amphotericin B regimen.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Candida albicans; Case-Control Studies; Catheterization, Central Venous; Catheters, Indwelling; Child; Child, Preschool; Drug Resistance, Microbial; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Immunosuppressive Agents; Infant; Logistic Models; Male; Middle Aged; Neutropenia; Prognosis; Retrospective Studies; Risk Factors; Shock, Septic; Treatment Outcome

To determine the epidemiology of candidemia in our neonatal intensive care unit; to compare risk factors, clinical presentation, and outcomes for neonates infected with Candida albicans, Candida parapsilosis, and coagulase-negative staphylococcus (CoNS); and to suggest a rational approach to empiric antifungal therapy of neonates at risk for nosocomial infection.. Retrospective chart review of all neonatal intensive care unit patients with systemic candidiasis or CoNS infection between January 1, 1995 and July 31, 1998 at Duke University Medical Center.. Fifty-one patients were reviewed. Nine of 19 patients infected with C parapsilosis and 5 of 15 patients infected with C albicans died of fungemia. Seventeen neonates had >2 positive cultures for CoNS obtained within 96 hours and 1 died. There was no statistically significant difference in birth weight, gestational age, or age at diagnosis between patient groups; however, candidemic patients had a sevenfold higher mortality rate. Before diagnosis, candidemic patients had greater exposure to systemic steroids, antibiotics, and catecholamine infusions. Of the 51 patients, 32 received third-generation cephalosporins in the 2 weeks before diagnosis and 19 did not. Twenty-nine of the 32 who were treated with third-generation cephalosporins subsequently developed candidemia, while candidemia occurred in only 5 of 19 patients who were not treated with cephalosporins. At the time of diagnosis, candidemic patients were more likely to have required mechanical ventilation and were less likely to be tolerating enteral feeding. Multivariate clustered logistic regression analysis revealed that candidemic patients had more exposure to third-generation cephalosporins. Once the clinician was notified of a positive blood culture for Candida, patients infected with C parapsilosis retained their central catheters longer than patients infected with C albicans.. In this retrospective review, we were able to identify aspects of the clinical presentation and medication history that may be helpful in differentiating between candidemia and CoNS bacteremia. Those key features may be used by clinicians to initiate empiric amphotericin B therapy in premature neonates at risk for nosocomial infections. Prolonged use of third-generation cephalosporins was strongly associated with candidemia. There was no statistically significant difference in the morbidity and mortality between patients infected with C parapsilosis and those infected with C albicans. Observed delays in removal of the central venous catheter may have contributed to finding a mortality rate from C parapsilosis that was higher than was previously reported.

Topics: Amphotericin B; Analysis of Variance; Anti-Bacterial Agents; Antifungal Agents; Bacteremia; Candida; Candida albicans; Candidiasis; Catheterization, Central Venous; Cephalosporins; Cross Infection; Diagnosis, Differential; Fungemia; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Logistic Models; Retrospective Studies; Risk Factors; Staphylococcal Infections

We report the first case of fungemia due to Candida catenulata, a contaminant of dairy products. C. catenulata was isolated from three blood cultures of a patient with gastric cancer. The patient failed to respond to fluconazole but recovered after treatment was switched to amphotericin B. In vitro, C. catenulata was susceptible to amphotericin B and itraconazole and was also susceptible to fluconazole in dose-dependent manner. The likely portal of entry was the digestive tract, as the patient often ate cheese and had multiple gastric ulcerations.

Topics: Adult; Amphotericin B; Antifungal Agents; Blood; Candida; Candidiasis; Female; Fungemia; Humans; Stomach Neoplasms

Twelve cases of Trichosporon spp. fungemias occurring in a national cancer institution within 10 years are described. The trend of hematogenous trichosporonosis within the last 10 years is increasing. While no cases occurred in 1988-1991, after 1991, Trichosporon spp. was the most common species among non-Candida spp. fungemias in 1993-1997. The 12 cases of fungemia included 5 that started while the patients were receiving prophylaxis with oral itraconazole, and 2 appeared despite empiric therapy with amphotericin B. Five of the 12 fungemias were catheter associated. Risk factors for fungemia were: central venous catheter, broad-spectrum antibiotics (third-generation cephalosporins plus aminoglycoside); all but 1 had neutropenia and were receiving antineoplastic chemotherapy. All but 2 of the patients died of systemic fungal infection (83.3% mortality). Amphotericin B was administered to all but 1 patient, who was not treated because he died the day after his culture was found to be positive for T. beigelii, before antifungals were administered. All cases infected with T. pullulans were catheter related, and all these patients died. One of the remaining 9 fungemias was caused by T. capitatum (Blastoschizomyces capitatus), and 8 by T. beigelii. Only 2 patients were cured, 1 with a combination therapy with amphotericin B plus fluconazole, and 1 with amphotericin B monotherapy. Several risk factors (neutropenia, acute leukemia, prior therapy or prophylaxis with antifungals and catheter as source of fungemia, breakthrough fungemia) were significantly associated with Trichosporon spp. fungemia, in comparison to 63 C. albicans candidemia occurring in the same period at the same institution. Attributable mortality of hematogenous trichosporonosis was also significantly higher (83.3% vs. 15.8%, P<0.001) than that of hematogenous candidiasis.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Catheterization, Central Venous; Catheterization, Peripheral; Cause of Death; Cephalosporins; Chemoprevention; Female; Fungemia; Humans; Itraconazole; Male; Middle Aged; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Risk Factors; Trichosporon

Histoplasmosis is an important systemic fungal infection, particularly among immunocompromised individuals, who may develop a progressive disseminated form which is often fatal if it is untreated. In such patients, the detection of antibody responses for both diagnosis and follow-up may be of limited use, whereas the detection of Histoplasma capsulatum var. capsulatum antigens may provide a more practical approach. We have recently described an inhibition enzyme-linked immunosorbent assay (ELISA) for the detection in patients' sera of a 69- to 70-kDa H. capsulatum var. capsulatum-specific antigen which appears to be useful in diagnosis. To investigate its potential for the follow-up of histoplasmosis patients during treatment, antigen titers in the sera of 16 patients presenting with different clinical forms of histoplasmosis were monitored at regular intervals for up to 80 weeks. Sera from four of five patients with the acute form of the disease showed rapid falls in antigenemia, becoming antigen negative by week 14 (range, weeks 10 to 16). Sera from four patients with disseminated histoplasmosis showed falls in antigen levels; three of them became antigen negative by week 32; the fourth patient became negative by week 48. In contrast, antigen titers in four of six AIDS patients with the disseminated form of the disease remained positive throughout follow-up. Sera from only one patient who presented with the chronic form of the disease were analyzed, and this individual's serum became antigen negative by week 9. The inhibition ELISA is shown to be of particular use in the monitoring of non-AIDS patients with the acute and disseminated forms of the disease and may complement existing means of follow-up.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antigens, Fungal; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Fungemia; Histoplasma; Histoplasmosis; Humans; Infant; Itraconazole; Male; Sensitivity and Specificity; Time Factors

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Chemistry, Pharmaceutical; Dyspnea; Fungemia; Humans; Male; Middle Aged

All cases of infective endocarditis occurring from January 1990 to December 1996 at our institution were reviewed, with a special focus on fungal endocarditis. Five critically ill children with fungal endocarditis and eleven children with bacterial endocarditis were recorded. The proportion of fungal endocarditis in our series was 5/16 (31%) and Candida albicans (4/5) was the most common fungal pathogen. Only one patient required heart surgery because of a loose patch but all the others were treated only by medical management for cure. The hospital survival rate was 80% (4/5) and the overall long-term survival rate was 60% (3/5) with only one death directly related to fungal infection.. Despite the small number of cases, a sole medical approach including amphotericin B and long-term fluconazole prophylaxis for the treatment of fungal endocarditis in critically ill children seems to offer an alternative to surgical treatment which may be kept for failure of medical treatment.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Endocarditis; Female; Fungemia; Heart Defects, Congenital; Humans; Male; Postoperative Complications; Retrospective Studies; Switzerland; Treatment Outcome

We report the case of a patient who, following surgical removal of an extensive tumour of the bowel, developed fungaemia. The yeast was isolated from repeated blood and urine cultures and identified as Rhodotorula rubra on the basis of macroscopic and microscopic features. Following treatment with amphotericin B, the patient's condition improved and the cultures became sterile.

Topics: Amphotericin B; Antifungal Agents; Fungemia; Humans; Immunocompromised Host; Intestinal Neoplasms; Male; Middle Aged; Mycoses; Opportunistic Infections; Postoperative Complications; Rhodotorula

The purpose of this study was to identify the pharmacokinetics of Amphotericin B Colloidal Dispersion in patients undergoing bone marrow transplantations with systemic fungal infections and to assess the influence of ABCD on renal function. Seventy-five patients (42 females, 33 males) with a median age of 34.5 years and median weight of 70.0 kg were enrolled in the study. The plasma concentration data was available in 51/75 patients and was best described by a two-compartment model; both plasma clearance and volume of distribution increased with escalating doses; the overall average terminal elimination half-life was 29 h. Serum creatinine values over the duration of therapy were available in 59/75 patients. Overall, there was no net change in renal function over the duration of therapy.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Child; Child, Preschool; Creatinine; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Combinations; Female; Fungemia; Humans; Kidney; Kidney Function Tests; Male; Middle Aged; Mycoses; Treatment Outcome

Twenty-two candidemia happened in our hospital from January 1997 to may 1998. We studied the clinical evolution of the patients and the sensitivity of the yeasts to antifungal therapy (Fungitest and E-Test method). We found 11 Candida albicans (CA), 10 Candida non albicans (CNA) (3 C. glabrata, 2 C. parapsilosis, 4 C. tropicalis, 1 C. krusei) and 1 Saccharomyces cerevisiae. The mean age of the patients was 56.4 years. There were 13 men and 9 women. We found one group of 8 (36.4%) oncohematological patients, one group of 8 (36.4%) patients with abdominal surgery, one group of 3 (13.6%) children and one group of 3 adults (13.6%) who spent more than 10 days in an intensive care unit. Ten times, these candidemia were associated with bacteriemia, 4 times with several bacteria. Three patients died because of the candidemia, 2 times with CNA and one time with CA. There wasn't any resistance to amphotericin B or ketoconazole. All the CA and 3 CNA (30%) remained sensitive to the four antifungal drugs we used (amphotericin B, ketoconazole, fluconazole, itraconazole). The 3 C. glabrata and the C. krusei were resistant or limit to fluconazole. Since the generalization of the use of fluconazole, the epidemiology is marked by the emergence of new strains of CA with high level of resistance to azols, and of CNA. In our hospital, the CA remain preponderant and only the CNA are resistant to fluconazole making difficult the choice of empiric treatment for serious fungemia.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Child, Preschool; Female; Fluconazole; France; Fungemia; Hospitals, University; Humans; Infant; Itraconazole; Ketoconazole; Male; Microbial Sensitivity Tests; Middle Aged; Mycoses; Postoperative Complications; Saccharomyces cerevisiae

Yeast fungemia has increased markedly in the last few years. Currently, Candida spp. is one of the microorganisms recovered most frequently from blood cultures. To better know the prevalence of yeast fungemia in our country we conducted a cross-sectional study with yeasts recovered from blood cultures obtained during a 3-month period from 39 hospitals in the Spanish public health hospital net. A total of 153 yeasts were recovered (59 were C. albicans, 53 C. parapsilosis, and 41 other species of yeasts). The percentage of males was 64.1. Mean age was 50.8 years. Factors associated with the appearance of fungemia were previous antibiotic therapy (83.7%), venous catheter (66%), previous bacterial infections (47.7%), and parenteral nutrition (40.5%). The recovery of C. albicans was independently associated with the admission to ICU, PDA and presence of urological/renal disease; C. parapsilosis was independently associated with the presence of hematological disease. The susceptibility studies of these strains recovered from blood cultures showed that in vitro resistance to amphotericin B and 5-fluorocytosine are practically nonexistent and that resistance to azole compounds is low. Multicentric epidemiologic studies are still necessary in this field of Microbiology.

Topics: Adult; Age Factors; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross-Sectional Studies; Drug Resistance, Microbial; Female; Fluconazole; Flucytosine; Fungemia; Humans; Itraconazole; Male; Middle Aged; Mycoses; Sex Factors; Spain; Yeasts

Topics: Aged; Amphotericin B; Fatal Outcome; Fungemia; Humans; Hyperkalemia; Male; Mycoses; Renal Dialysis; Trichosporon

Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and tumor necrosis factor-soluble receptor (TNF-sR), and adhesion molecules, e.g. vascular adhesion molecule-1 (VCAM-1) and E-selectin, play an important role in the pathogenesis of bacterial sepsis. Experimental data on cytokine expression during candidaemia are controversial. In this study, plasma concentrations of cytokines and adhesion molecules were compared between patients with sepsis due to Candida albicans and bacterial sepsis. Plasma levels of TNF-alpha, TNF-sR, IL-6, VCAM-1 and E-selectin, were determined in 20 patients with sepsis due to C. albicans, in 20 patients with bacterial sepsis, and in 20 controls on days 1, 7 and 14. On day 1, elevated plasma levels of TNF-alpha, TNF-sR and IL-6 were detected in both sepsis groups compared to controls. On day 1, VCAM-1 levels were higher, and E-selectin levels were lower in patients with Candida sepsis than in patients with bacterial sepsis (p < 0.05). At any time, VCAM-1 levels were significantly greater in patients with Candida sepsis than in patients with bacterial sepsis (p < 0.05). Non-survivors, regardless of the etiology of sepsis, had higher blood levels of IL-6, TNF-sR and E-selectin than survivors. The cytokines, TNF-alpha, IL-6 and TNF-sR, and the adhesion molecules, VCAM-1 and E-selectin, are involved in sepsis due to C. albicans as in bacterial sepsis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Bacteremia; Candidiasis; Cell Adhesion Molecules; Cytokines; Female; Fluconazole; Fungemia; Humans; Male; Middle Aged

A retrospective study of 76 episodes of candidemia in 73 patients with underlying hematological malignancy, from 1988 until 1997, has been conducted to evaluate the clinical characteristics and to ascertain the variables related to the onset and the outcome of candidemia. The most frequent malignancy was acute myeloid leukemia (29 episodes). Candidemia developed mainly during aplasia in patients refractory to chemotherapy (42%). In 65 episodes (86%) the patients were neutropenic (ANC <1 x 10(9)/l) before the candidemia diagnosis for a median time of 13 d, and in 53 episodes (70%) at microbiological diagnosis of candidemia ANC was <1 x 10(9)/l. Candida albicans was the most frequently isolated etiologic agent (31 episodes), but C. non-albicans species sustained the majority of candidemia. Seventeen candidemias developed during azoles prophylaxis. One month after the diagnosis of candidemia, 26 patients died. In 19 cases, death was attributable to candidemia. The case-control study demonstrated, at univariate analysis, that the colonization with Candida. spp. (p=0.004), antimycotic prophylaxis (p=0.01), presence of central venous catheter (p=0.01), neutropenia (p=0.002), and the use of glycopeptide (p=0.0001) increased the risk of candidemia. Using multivariate regression analysis only colonization with Candida spp. and the previous therapy with glycopeptide were associated with a significantly increased risk. Acute mortality, expressed by a cumulative probability of survival at 30 d from diagnosis of candidemia, was 0.67 (95% C.I. 0.55-0.77) and was significantly reduced in patients with neutrophils <1 x 10(9)/l when compared to those with neutrophils >1 x 10(9)/l (p at Mantel-Cox=0.029). Overall cumulative probability of survival at 1 yr was 0.38 (95% C.I. 0.27-0.49) and only the treatment with Amfotericin B significantly reduced the risk of death.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Case-Control Studies; Catheterization, Central Venous; Female; Fungemia; Glycopeptides; Hematologic Neoplasms; Humans; Life Tables; Male; Middle Aged; Neutropenia; Parenteral Nutrition, Total; Proportional Hazards Models; Regression Analysis; Retrospective Studies; Risk Factors; Superinfection; Survival Analysis; Survival Rate; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Drug Carriers; Fatal Outcome; Fungemia; Humans; Lipids; Neoplasms; Treatment Failure

Forty-five cases of fungaemia due non-albicans Candida spp. (NAC) in a single National Cancer Institution within 10 years were analysed for aetiology, risk factors and outcome. There had been 12 cases of fungaemia that were due to C. krusei, 14 due to C. parapsilosis, 7 due to C. (T.) glabrata, 6 to C. tropicalis, 2 to C. guillermondii, 2 to C. lusitaniae, 1 to C. stellatoidea, and 1 to C. rugosa. Comparison of 45 NAC fungaemia with 75 episodes of C. albicans fungaemia revealed differences only in two risk factors: previous empiric therapy with amphotericin B (16.0 vs 2.2%, P<0.01) appeared more frequently in cases of C. albicans fungaemia, and prior prophylaxis with fluconazole (8.9 vs 0%, P<0.02) was conversely more frequently observed with NAC. The incidence of other risk factors, such as underlying disease, chemotherapy, antibiotic prophylaxis or therapy, treatment with corticosteroids, catheter insertion, mucositis, cytotoxic chemotherapy, and neutropenia, was similar in both groups. There was no difference either in attributable or in overall mortality between NAC and C. albicans fungaemia in our cancer patients.

Topics: Adrenal Cortex Hormones; Amphotericin B; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Agents; Candida; Candida albicans; Candidiasis; Catheterization; Chi-Square Distribution; Cross Infection; Fluconazole; Fungemia; Humans; Incidence; Neoplasms; Neutropenia; Outcome Assessment, Health Care; Prospective Studies; Risk Factors; Slovakia

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Clotrimazole; Community-Acquired Infections; Drug Resistance, Microbial; Drug Resistance, Multiple; Fluconazole; Fungemia; Humans; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged

Outcome for 105 patients with candidemia treated with amphotericin B was correlated with amphotericin B in vitro susceptibility results. Thirty-three patients had microbiologic failure, which was defined as persistence of Candida in the bloodstream despite > or = 3 days of amphotericin B. Amphotericin B minimum inhibitory concentrations (MICs) were determined by the National Committee for Clinical Laboratory Standards methodology. After determination of MICs, the minimal lethal concentrations (MLCs) were determined. The isolates tested yielded a narrow range of amphotericin B MICs (0.06-2 microg/mL); only 5% (5/105) exhibited MICs > or = 1 microg/mL. The MLC range, on the other hand, was significantly broader (0.125 to > 16 microg/mL); 24% (25/105) exhibited MLCs > or = 1 microg/mL. The strongest predictor for microbiologic failure was 48-h MLC (P < .001), followed by 24-h MLC (P = .03) and 48-h MIC (P = .11). A resistant break point for amphotericin B of > 1 microg/mL for MLC and > or = 1 microg/mL for MIC could be inferred from this study.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Microbial; Fungemia; Humans; Microbial Sensitivity Tests; Predictive Value of Tests; Sensitivity and Specificity; Treatment Failure; Treatment Outcome

Forty-one episodes of breakthrough fungaemia occurring over a 7.5 year period in the National and St Elizabeth's Cancer Institutes in Bratislava, Slovakia, were analysed. Five of them occurred during prophylaxis with fluconazole (one Torulopsis glabrata, one Hansenula anomala, two Candida krusei and one Candida parapsilosis), ten with itraconazole (three Trichosporon pullulans, one Trichosporon beigelii, one Cryptococcus laurentii, three Candida albicans and two T. glabrata), 11 during prophylaxis with ketoconazole (one Candida norvegenesis, one C. parapsilosis, one C. krusei, one Candida tropicalis, five C. albicans, one Candida stellatoidea and one C. laurentii and 15 during empirical therapy with amphotericin B (ten C. albicans, two T. beigelii and three Candida lusitaniae). The most frequent risk factors for breakthrough fungaemia were neutropenia, previous therapy with multiple antibiotics and recent catheter insertion. Comparing these episodes with 38 non-breakthrough fungaemias (appearing at the same institute in the same period) differences in certain risk factors were noted: breakthrough fungaemias were more frequently observed in patients with acute leukaemia (39.0% vs 5.2%, P < 0.001), mucositis (34.2% vs 13.1%, P < 0.05), prophylaxis with quinolones (58.5% vs 15.8%, P < 0.0001) and catheter-associated infections (29.3% vs 2.6%, P < 0.003). In this subgroup overall mortality (36.6% vs 28.8%) or early attributable mortality (22.0% vs 23.6%) were not significantly different.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Cross Infection; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Fluconazole; Fungemia; Humans; Incidence; Itraconazole; Ketoconazole; Male; Mitosporic Fungi; Neoplasms; Pichia; Retrospective Studies; Risk Factors; Slovakia; Treatment Outcome

We retrospectively analyzed 13 episodes of candidemia observed between July 1990 and July 1995 in human immunodeficiency virus (HIV)-infected adults. Candidemia was nosocomially acquired by 11 patients, among whom nine had a central venous catheter (CVC). Twelve cases were of stage C2/C3 according to the 1993 classification of the Centers for Disease Control and Prevention. The median CD4+ cell count was 10/mm3 (range, 3-400/mm3). Causative species were Candida albicans in nine episodes and Candida glabrata and Candida krusei in two episodes each. Eleven episodes occurred in 11 patients who had previously received fluconazole (mean total dose, 7.4 g), including the four episodes caused by non-albicans species. Outcome did not differ according to the administered antifungal therapy. CVCs were removed from seven patients (78%). The overall mortality was 38%. Candidemia is a potentially lethal nosocomial complication during late-stage AIDS and can be due to C. albicans and non-albicans strains.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Catheterization, Central Venous; CD4 Lymphocyte Count; Cross Infection; Female; Fluconazole; Fungemia; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors

A patient with myelofibrosis complicated by recurrent candidemia died despite treatment with amphotericin B and fluconazole. Autopsy revealed systemic candidiasis with fungal verrucae in the right ventricle and the root of the pulmonary artery. The strains of Candida albicans isolated from the blood had become resistant to amphotericin B and fluconazole during therapy, as well as to other azole antifungals that had not been used. Pulsed-field gel electrophoresis showed that the resistant isolates had the same genotype as the sensitive strains isolated before treatment, but a chromosomal change in >2.0 Mb-bands was observed after treatment. It was thus proved that these repeatedly isolated C. albicans strains which were causing the continued fungemia in our patient were all the same strain and were acquiring resistance to antifungal agents during the therapy.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; DNA, Fungal; Drug Resistance, Microbial; Electrophoresis, Gel, Pulsed-Field; Fluconazole; Fungemia; Humans; Male; Middle Aged; Primary Myelofibrosis

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Drug Combinations; Fungemia; Humans; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols; Rhodotorula

To identify areas of consensus and controversy in the management of neonatal candidiasis.. A questionnaire was distributed to US-based members of the Pediatric Infectious Diseases Society and a sampling of US neonatologists.. Three hundred eighty evaluable questionnaires were returned (42% of those mailed). Ninety-five percent of respondents have cared for an infant with systemic candidiasis in the past 2 years. Fluconazole and liposomal amphotericin are used to some extent by 90 and 69% of respondents, respectively. A single blood culture positive for Candida led to a recommendation for immediate treatment by 99%; amphotericin B was the preferred therapy for candidemia (88%). More than 80% of respondents would request cerebrospinal fluid, urine and repeat blood cultures and ophthalmologic examination in the evaluation of candidemia. If a cerebrospinal fluid culture is positive, 25% would use amphotericin B alone whereas 62% would add flucytosine. For candiduria Society members chose fluconazole therapy more often than did neonatologists, 23% vs. 3.4% (P<0.001). There was no consensus concerning duration of therapy, use of an amphotericin B test dose or management of a central catheter in place during candidemia.. Systemic candidiasis in neonates is a frequently encountered clinical problem. There is agreement that prompt therapy with amphotericin B is required if a blood culture is positive for Candida and that such infants require additional evaluations. Other antifungals (fluconazole, liposomal amphotericin B) are used to some extent in this population. Many issues in management have no clear consensus and warrant further research.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Decision Making; Fungemia; Humans; Infant, Newborn; Surveys and Questionnaires

The paper presents an analysis of fungemia cases which were caused by C. parapsilosis in a cancer center within 10 years, with the aim to compare risk factors and the outcome with fungemias caused by C. albicans and other non-albicans Candida spp. fungemias. Before 1990 (1988-1989) in our institutes C. parapsilosis fungemias were not observed at all. During 1990-1997, the proportion of C. parapsilosis among fungemias increased, in 1990-1993 from 0% to 7.1% in 1996-1997 to 14.2-15%. It represents 25% out of non-albicans Candida spp. fungemias and 7.9% out of all fungemias and is the third commonest pathogen after C. albicans (50.5%) and C. krusei (9.9%). Two from eight (25%) C. parapsilosis fungemias were breakthroughs, one appeared during prophylaxis with ketoconazol and one with fluconazol. Considering the proportion of C. parapsilosis among blood cultures, 13 of 170 blood cultures contained C. parapsilosis (6.6% among all yeasts from blood cultures). C. parapsilosis was the second commonest fungal organism isolated from blood cultures (after C. albicans) in our cancer center. Infected vascular catheters were surprisingly not the major risk factor: central venous catheters were documented as a source in two cases only. The commonest risk factors were similar to those occurring with other fungemias--such as preceding antimicrobial therapy (62.5%), neutropenia (50%) and prior prophylaxis with azoles.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candidiasis; Child; Female; Fluconazole; Fungemia; Humans; Incidence; Male; Microbial Sensitivity Tests; Neoplasms; Risk Factors

Infections with fluconazole-resistant Candida albicans isolate have rarely been described in clinical settings other than oropharyngeal candidiasis in patients with late-stage AIDS. We report on two patients with leukemia who developed fungemia caused by fluconazole-resistant C. albicans after receiving fluconazole prophylaxis (400 mg/day) and empiric amphotericin B therapy (0.5 mg/kg of body weight per day). The fluconazole MICs for the isolates were > or = 64 micrograms/ml, and the isolates were resistant to other azoles and had membrane sterol changes consistent with a mutation in the delta 5,6-sterol desaturase gene. The lack of ergosterol in the cytoplasmic membrane of the fluconazole-resistant strains also imparted resistance to amphotericin B. Both patients were successfully treated with high-dose amphotericin B (1 to 1.25 mg/kg/day) and flucytosine (150 mg/kg/day).

Topics: Adolescent; Adult; Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Drug Resistance, Multiple; Female; Fluconazole; Flucytosine; Fungemia; Humans; Leukemia, Myeloid, Acute; Male; Mice; Microbial Sensitivity Tests; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Virulence

Thirty-seven episodes of hospital-acquired candidaemia, which occurred over a two-year period, were reviewed. The predominant risk factors were previous antibiotic therapy (100%), indwelling central venous catheter (94.6%), parenteral hyperalimentation (78.3%) and preceding surgery (51.4%). Eighty-nine percent of the patients had three or more risk factors. Candida albicans (56.8%), and Candida tropicalis (13.5%) were the most common isolates. Mortality was 48.6%. No significant difference was observed between patients treated with amphotericin B and those treated with fluconazole. The age of the patient, species of Candida, number of positive blood cultures for Candida, concomitant bacteraemia, and antifungal therapy did not have any significant effect on outcome. Our results were similar, in many aspects, to those reported from developed countries.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Cross Infection; Female; Fluconazole; Fungemia; Humans; Infant; Male; Middle Aged; Qatar; Risk Factors

A PCR assay was developed for the detection and identification of Candida and Aspergillus species. The design of the oligonucleotide primer pair as well as the species-specific probes used for species identification was derived from a comparison of the sequences of the 18S rRNA genes of various fungal pathogens. The primers targeted a consensus sequence for a variety of fungal pathogens. The assay was tested for sensitivity and specificity with 134 fungal and 85 nonfungal isolates. To assess clinical applicability, 601 blood samples from four defined groups were tested: group A (n = 35), controls; groups B to D (n = 86), patients with febrile neutropenia, without fungal colonization (group B; n = 29) and with fungal colonization (group C; n = 36); and patients with documented invasive fungal infection (IFI) (group D; n = 21). The assay detected and, by species-specific hybridization, identified most of the clinically relevant Candida and Aspergillus species at 1 CFU/ml of blood. Amplification was 100% sensitive for all molds and yeasts tested, with Histoplasma capsulatum being the only non-Aspergillus species hybridizing with the Aspergillus spp. probe. None of 35 group A patients and only 3 of 65 group B and C patients were PCR positive. The sensitivity of the assay for specimens from patients with IFI (21 patients in group D) was 100% if two specimens were tested. For specificity, 3 of 189 specimens from patients at risk but with negative cultures were positive by the assay, for a specificity of 98%. PCR preceded radiological signs by a median of 4 days (range, 4 to 7 days) for 12 of 17 patients with hepatosplenic candidiasis or pulmonary aspergillosis. For the 10 patients with IFI responding to antifungal therapy, PCR assays became persistently negative after 14 days of treatment, in contrast to the case for 11 patients, who remained PCR positive while not responding to antifungal therapy. Thus, the described PCR assay allows for the highly sensitive and specific detection and identification of fungal pathogens in vitro and in vivo. Preliminary data from the screening of a selected group of patients revealed some value in the early diagnosis and monitoring of antifungal therapy.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Candida; Candidiasis; DNA, Fungal; Fluconazole; Fungemia; Fungi; Humans; Molecular Sequence Data; Neutropenia; Oligonucleotide Probes; Polymerase Chain Reaction; RNA, Ribosomal, 18S; Sensitivity and Specificity

Trichosporon beigelii is an uncommon cause of sepsis in low-birth-weight infants. We present two cases of neonatal trichosporonosis and two cases of neonatal trichosporon colonization to familiarize neonatologists with this entity and to discuss management considerations. A 23-week-gestation male developed clinical evidence of sepsis on day 10 and was found to have "yeast" growing in a blood culture on day 12. Despite receiving amphotericin B, he expired within 2 days, at which time the organism was identified as T. beigelii. A 23-week gestation female developed fungal septicemia in the second week of life, while being treated for persistent bacterial sepsis. Candida albicans grew from blood culture, while T. beigelii grew from suprapubic urine, tracheal aspirate, and umbilical catheter tip cultures. She died 2 days later despite therapy with amphotericin B, at which time the fungal isolates were correctly identified. Two other infants were found to have colonization of central vascular catheters, without evidence of invasive disease. Trichosporon infections in neonates have been almost uniformly fatal. Most strains of T. beigelii are relatively resistant to amphotericin B and may be confused with Candida sp. on initial culture examinations. Therefore, delays in appropriate treatment may occur. We discuss treatment options, including alternative antifungal drugs, as well as possibilities for combination therapy.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Catheterization, Central Venous; Catheterization, Peripheral; Diagnosis, Differential; Drug Combinations; Drug Resistance, Microbial; Equipment Contamination; Fatal Outcome; Female; Fungemia; Humans; Infant, Low Birth Weight; Infant, Newborn; Male; Methicillin Resistance; Mycoses; Sepsis; Staphylococcal Infections; Staphylococcus epidermidis; Trachea; Trichosporon; Urine

Amphotericin B is still the first-line therapy for neonatal fungal infections. With several comparative trials of intralipid-based amphotericin B (IL-AmB) demonstrating its clinical effectiveness and reduced renal toxicity in adults, we examined the renal tolerance and infection outcome in low-birth-weight infants in our 48-bed NICU treated with IL-AmB. Over 2 years, 52 patients (58 courses) received > or = 10 days of IL-AmB. Nineteen charts (23 episodes) were randomly accessed and reviewed. Mean birthweight = 747 grams, gestational age = 25.6 weeks, total IL-AmB dosage = 19.8 +/- 3.3 mg/kg (n = 23); 20 of these episodes were fungal culture positive (9 fungemias). Only one patient (who died during therapy) had a rise in creatinine of > 0.3 mg/dL. Overall, serum creatinine decreased significantly after Day 10 of IL-AmB therapy, from 0.93 +/- 0.42 mg/dL at baseline, to 0.54 +/- 0.24 after 19 days of therapy (p < 0.0001). Serial urine output, serum potassium and potassium supplementation data showed no significant differences from baseline. No interruption of therapy nor infusion reactions occurred. Only one death occurred attributable to fungal infection. Intralipid-amphotericin B may provide an effective alternative in the antifungal therapy of low birthweight neonates, without nephrotoxicity. Further prospective, comparative trials are warranted.

Topics: Amphotericin B; Analysis of Variance; Antifungal Agents; Blood Urea Nitrogen; Candida albicans; Candidiasis; Chi-Square Distribution; Creatinine; Female; Fungemia; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Intensive Care Units, Neonatal; Kidney; Kidney Function Tests; Male; Registries; Retrospective Studies; Treatment Outcome; Urine

We report a case of maternal brain death at 25 weeks gestation in which aggressive maternal hemodynamic, respiratory, and metabolic support and tocolytic drug therapy resulted in prolongation of pregnancy for 25 days. The indication for delivery was torulopsis giabrata amnionitis, which may have occurred due to transmembrane or transplacental route. The baby was treated for fungal sepsis, and did well. Premature labor may occur spontaneously after maternal brain death, and may be precipitated by infection or by maternal drug therapy. The myriad of hemodynamic and endocrine issues associated with maternal brain death complicate the choice of tocolytic drugs, but this case illustrates that uterine activity can be successfully blocked, potentially diminishing risks to the newborn, following the tragedy of maternal brain death during pregnancy.

Topics: Adult; Amphotericin B; Brain Death; Candidiasis; Cerebral Hemorrhage; Disease-Free Survival; Fatal Outcome; Female; Fungemia; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Obstetric Labor, Premature; Pneumonia; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy Trimester, Second; Tocolysis

The case of a white-heroin addict who developed disseminated candidiasis following coinfection by Candida glabrata and Candida albicans is reported. Genomic random amplified polymorphic DNA typing suggested that the Candida glabrata blood isolates originated in the oral cavity of the patient. This case strengthens the evidence that Candida species other than Candida albicans can be involved in the pathogenesis of disseminated candidiasis in heroin addicts.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; DNA, Fungal; Fungemia; Heroin Dependence; HIV Seropositivity; Humans; Injections, Intravenous; Male; Mouth; Skin; Species Specificity

In the past, evidence of endogenous fungal endophthalmitis has been used as a guide to initiating potentially toxic antifungal therapy in patients with systemic fungal infections. Recently, however, a trend has developed to provide patients with antifungal therapy at the first evidence of fungal infection. The authors' study evaluates the incidence of endogenous fungal endophthalmitis in this setting.. The design is a retrospective review of the medical records of patients examined by the inpatient ophthalmology consultation service to rule out endogenous fungal endophthalmitis between January 1994 and April 1996 at the University of Michigan Hospitals, Ann Arbor, Michigan.. Two hundred fourteen eyes of 107 patients with a diagnosis of systemic fungal infection were studied.. A review of medical records was performed.. The findings of the ocular examination, the presence of risk factors for disseminated fungal infection, the type of antifungal therapy, and the source and identity of the isolated fungus were recorded.. The majority of patients examined had either fungal growth from blood cultures or evidence of deep tissue fungal infection. All patients in the study were at risk for fungal disease with each having at least one risk factor for disseminated fungal infection. Of the patients examined, 93.4% already were receiving systemic antifungal therapy at the time of ophthalmologic consultation. Only 3 (2.8%) of the 107 patients examined had chorioretinal findings consistent with early endogenous fungal endophthalmitis. None had intravitreous involvement, and the ocular findings did not change the course of therapy.. Early systemic treatment of deep tissue fungal infection appears to dramatically decrease the incidence of endogenous fungal endophthalmitis.

Topics: Administration, Oral; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Fungal; Female; Fluconazole; Flucytosine; Fungemia; Humans; Incidence; Infant; Injections, Intravenous; Male; Middle Aged; Retrospective Studies

Topics: Adult; Amphotericin B; Antifungal Agents; Fungemia; Histoplasma; Histoplasmosis; Humans; Itraconazole; Liver Transplantation; Male

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cross Infection; Fluconazole; Fungemia; Humans; Retrospective Studies; Risk Factors

To analyze the epidemiologic characteristics of non-neutropenic patients with candidemia in a general hospital and the advantages and disadvantages of treatment with amphotericin B or fluconazole.. A total of 62 adult non-neutropenic patients with candidemia and treated with amphotericin B (n = 35) or fluconazole (n = 27) were studied. All episodes were considered to be associated with infection in a vein catheter. The demographic characteristics, risk factors for the development of candidemia, Candida species recovered from blood culture, underlying diseases, and clinical manifestations in both groups were compared. The evolution regarding secondary effects developed with both drugs, therapy failures, long term complications, and overall mortality rate associated with candidemia were analyzed.. Both groups were comparable with the exception of the percentage of patients infected with species different from Candida albicans, which was higher in the group of patients who received amphotericin B (57%) than in the fluconazole group (26%) (p = 0.02), and in that patients with severe renal failure or AIDS had received preferentially fluconazole. There were no statistically significant differences regarding the evolution of patients treated with amphotericin B or fluconazole with the following factors: therapy failure (27% versus 19%; p = 0.7), overall mortality rate (40% versus 44%; p = 0.6), and mortality directly related to candidemia (33% versus 30%). Mortality was significantly higher among patients who had not their vein catheters removed early (78%) compared with those who had their vein catheters removed early (34%) (p = 0.01). Sixty-six percent of patients treated with amphotericin developed some severe secondary effect, whereas no patient in the fluconazole group developed such effects.. Both amphotericin B and fluconazole seem to be effective drugs for the treatment of vein catheter related candidemia in the non-neutropenic patient, although fluconazole is far less toxic. The early removal of the vein catheter plays a prognostic role with at least the same relevance than the type of antifungal therapy chosen.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Blood; Candida; Candida albicans; Candidiasis; Catheterization; Female; Fluconazole; Fungemia; Humans; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Time Factors

Invasive fungal infections occur frequently in neutropenic patients although only in recent years has the role of emerging fungi been clearly established. We describe two cases of fungemia caused by Trichosporon beigelii and Rhodotorula glutinis respectively in two neutropenic patients with hematological malignancies who were treated with amphotericin B. The first patient, with refractory multiple myeloma, died following massive pneumonia despite therapy with amphotericin B and granulocyte-colony stimulating factor (G-CSF); the second patient, with relapsed acute lymphatic leukemia and persistent fever without any other clinical evidence, finally recovered. Amphotericin B continues to be considered the "gold standard" in the treatment of invasive mycoses although other approaches need to be tested for refractory infections.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Female; Fungemia; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Multiple Myeloma; Neoplasm Recurrence, Local; Neutropenia; Pneumonia, Bacterial; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pseudomonas Infections; Rhodotorula; Treatment Outcome; Trichosporon

To study the clinical histories and courses of six patients with choroidal neovascularization secondary to endogenous Candida albicans chorioretinitis.. The medical records, fundus photographs, and fluorescein angiograms of six patients who developed C. albicans chorioretinitis secondary to candidemia and who subsequently developed choroidal neovascularization in one or both eyes were reviewed.. The six patients ranged in age from 18 to 79 years. Four were women and two men; all but one showed evidence of bilateral chorioretinal scarring secondary to C. albicans chorioretinitis. All patients had been treated successfully with systemic antifungal therapy (amphotericin B). Two weeks to two years after the chorioretinitis, choroidal neovascularization developed in one eye (four cases) or both eyes (two cases). The neovascularization on initial examination was subfoveal in four eyes, extrafoveal in three eyes, and juxtafoveal in one eye. Laser photocoagulation was used in four of the eight involved eyes. In these cases, the active choroidal neovascularization was brought under control. In one eye, the patient had submacular surgery for excision of the choroidal neovascular membrane. Final visual acuities ranged from 20/20 to 20/200 in treated eyes and from 20/50 to 20/400 in untreated eyes.. Choroidal neovascularization is a potential cause of late visual loss in patients who have had C. albicans sepsis and endogenous C. albicans chorioretinitis. Eyes that have chorioretinal scarring from C. albicans chorioretinitis should be watched for the development of choroidal neovascularization. Laser photocoagulation or perhaps surgical excision of the neovascular complex may be of benefit in selected cases.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Chorioretinitis; Choroid; Eye Infections, Fungal; Female; Fluorescein Angiography; Fundus Oculi; Fungemia; Humans; Laser Coagulation; Male; Middle Aged; Neovascularization, Pathologic; Visual Acuity

A 51-year-old man with acquired immunodeficiency syndrome and cytomegalovirus retinitis had bilateral endogenous fungal endophthalmitis. Cultures yielded Fusarium species. Histopathologic examination showed a severe necrotizing acute and granulomatous reaction, with numerous fungal elements in the retina and uveal tract. Fungal elements were seen in the lens, sclera, and emissarial vessels. Angiopathic infiltration by fungus and widespread thrombosis produced retinal and choroidal infarction. In some areas, fungal infection coexisted with cytomegalovirus retinitis. The bilateral distribution suggests hematogenous seeding of the eyes. The eye findings were the first clinically apparent manifestations of fungal disease in this patient.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cytomegalovirus Retinitis; Endophthalmitis; Eye; Eye Infections, Fungal; Fluconazole; Fungemia; Fusarium; Humans; Male; Middle Aged; Mycoses

To assess the changing epidemiology of candidemia in the 1990s, to evaluate the clinical implications for the presence of non-Candida albicans in blood, and to evaluate the presence of antifungal resistance in relation to prior antifungal administration.. Multicenter prospective observational study of patients with positive blood cultures for Candida species or Torulopsis glabrata.. Four tertiary care medical centers.. Four hundred twenty-seven consecutive patients were enrolled. The frequency of candidemia due to non-C. albicans species significantly increased in each hospital throughout the 3.5-year study period (P = 0.01). Thirteen percent of candidemias occurred in patients who were already receiving systemic antifungal agents. Candidemias developing while receiving antifungal therapy were more likely caused by non-C. albicans species than by C. albicans species (P = 0.0005). C. parapsilosis and C. krusei were more commonly seen with prior fluconazole therapy, whereas T. glabrata was more commonly seen with prior amphotericin B therapy. Candida species isolated during episodes of breakthrough candidemia exhibited a significantly higher MIC to the antifungal agent being administered (P < 0.001).. In this large scale study, the non-C. albicans species, especially T. glabrata, emerged as important and frequent pathogens causing fungemia. This finding has major clinical implications given the higher complication and mortality rate associated with the non-C. albicans species. The change in the pattern of candidemia might be partly attributed to the increase in number of immunocompromised hosts and the widespread use of prophylactic or empiric antifungal therapy. This is an ominous sign given the in vitro resistance of the non-C. albicans species to currently available antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Drug Resistance, Microbial; Fluconazole; Fungemia; Humans; Incidence; Microbial Sensitivity Tests; Multivariate Analysis; Prospective Studies; Risk; Risk Factors

A 35-year-old man with B lymphoblastic lymphoma was treated with bone marrow transplant and aggressive chemotherapy. He developed a Fusarium infection of the great toenail. Septicemic dissemination of a Fusarium sp. occurred 9 months later during a lymphoma relapse. The clinical course of the hyalohyphomycosis was then rapidly fatal despite institution of amphotericin B therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Bone Marrow Transplantation; Fatal Outcome; Foot Dermatoses; Fungemia; Fusarium; Humans; Immunocompromised Host; Lymphoma, B-Cell; Male; Mycoses; Neoplasm Recurrence, Local; Onychomycosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma

When a diagnosis of invasive candidiasis has been made, treatment with toxic fungicidal agents is inevitable. The crucial decision of when to stop such treatment is difficult to make, because cultures are often negative despite ongoing invasive candidiasis and can therefore not be used as a reliable parameter of effective therapy. In the present study, the use of PCR in monitoring the therapeutic efficacy of antifungal treatment with liposomal amphotericin B was evaluated by using neutropenic mice with systemic candidiasis. Blood cultures of infected mice treated with different doses of liposomal amphotericin B were only positive at the early onset of the infection process and became sterile within 3 days; this was true even with mice treated with 1 mg of liposomal amphotericin B per kg of body weight that experienced a relapse of infection 14 days later. A significant correlation between presence of Candida albicans in the kidneys and PCR results obtained with blood was demonstrated. Thus, PCR results obtained with blood samples correlated well with the therapeutic efficacy of antifungal treatment.

Topics: Amphotericin B; Animals; Antifungal Agents; Base Sequence; Candida albicans; Candidiasis; DNA Primers; DNA, Fungal; Evaluation Studies as Topic; Female; Fungemia; Liposomes; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Mycology; Neutropenia; Polymerase Chain Reaction; Time Factors

Topics: Amphotericin B; Antifungal Agents; Female; Fungemia; Humans; Leukemia, Myeloid, Acute; Middle Aged; Pichia

We describe a case of candidaemia in a paediatric cystic fibrosis (CF) patient with a totally implantable vascular access (TIVA). Serial quantitative blood cultures during therapy with amphotericin B delivered via the catheter suggested that the patient was responding to therapy. The TIVA was finally removed because of persistent fever, but its culture remained sterile. Randomly amplified polymorphic DNA (RAPD) analysis of Candida albicans from various anatomical sites showed that the patient's sputum was the most likely source of TIVA contamination. Investigation of TIVA-related candidaemia by molecular analysis could guide rational antifungal chemoprophylaxis of TIVA-related candidaemia.

Topics: Amphotericin B; Candidiasis; Catheters, Indwelling; Child; Cystic Fibrosis; DNA, Fungal; Female; Fungemia; Humans

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Drug Resistance, Microbial; Female; Fluconazole; Fungemia; Humans; Middle Aged

In recent decades an increase in the incidence of fungal infection has been reported. We retrospectively analyzed 41 patients with candidemia seen at Basel University Hospital over a six-year period. 1.2-6.7 candidemias per 10000 admissions were observed. In contrast to other studies, there was no increase during the study period. Out of 41 patients, 19 were hospitalized in ICUs. All patients had risk factors such as intravascular catheters (92.7%), antibiotic therapy (88%), immunosuppressive therapy (31%), indwelling Foley catheters (54%) and previous surgery (63%). The most frequent symptoms were fever with rigor, tachycardia and hypotension. The isolates were Candida albicans (n = 28), Torulopsis glabrata (n = 5), C. krusei (n = 3), C. parapsilosis (n = 2), C. guilliermondii, C. kefyr and C. lusitaniae (n = 1 each). In 22 patients, candida colonization had been documented and 5 patients had superficial mucocutaneous candidiasis before candidemia. The initial foci were the gastrointestinal tract (n = 13), an intravascular catheter (n = 8), the urinary tract (n = 5), the respiratory tract, or intravenous drug use (n = 3 each). Out of 32 patients who were treated either with amphotericin B or fluconazole, 13 died. 5 of the untreated patients died, in 3 instances before microbiological diagnosis. The mortality was similar for treatment with amphotericin B and with fluconazole (50% vs. 33%) (p = 0.3).

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; Female; Fluconazole; Fungemia; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Treatment Outcome

Mycethemia was diagnosed in 56 burn patients between 1958 and 1992. The overall incidence was 0.39% and the mortality rate was 39.29%. Candida albicans, constituting for 75% of cases, was most common encountered. The incidence was 0.26% and the mortality 72.73% in years before 1985, while that in the years after 1985 were 0.58% and 17.65%, respectively. The differences are of significance (P < 0.01) predisposing. The clinical characteristics were summed up, and the causes, clinical diagnosis and treatment were studied and discussed.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Burns; Candidiasis; Child; Child, Preschool; Female; Fungemia; Humans; Infant; Male; Middle Aged

The risk factors for systemic fungal infections were analysed retrospectively in 186 orthotopic liver transplant procedures performed in 152 patients between June 1985 and January 1993. The total incidence of systemic fungal infections was 16.5% (25/152). The incidence of disseminated candidiasis, aspergillosis, and combined candidiasis and aspergillosis was 6.5% (n = 10), 7.2% (n = 11) and 2.6% (n = 4), respectively. Mortality associated with systemic fungal infections was 80% (20 of 25 patients). There were ten cases of disseminated candidiasis, with 4 patients surviving, and 11 cases of invasive aspergillosis, with 1 patient surviving. All patients with combined systemic fungal infection died. To identify perioperative risk factors, 39 variables were used to compare patients with systemic fungal infections versus those without fungal infections. Fourteen variables were significantly associated with systemic fungal infections by univariate analysis. A consecutive logistic regression analysis revealed that the amount of fresh frozen plasma transfused due to poor initial function of the allograft and acute renal failure requiring hemofiltration were independently significant risk factors for systemic fungal infections. There was no statistical correlation between systemic fungal infections and the underlying liver disease, previous long-term corticosteroids and the postoperative immunosuppressive therapy. Risk factors identified in this study should be considered in the postoperative care of the individual liver transplant recipient. In our study a poor initial function of the hepatic allograft substantially increased the risk of systemic fungal infection.

Topics: Adult; Amphotericin B; Analysis of Variance; Antifungal Agents; Female; Fungemia; Humans; Incidence; Liver Transplantation; Logistic Models; Male; Middle Aged; Mycoses; Opportunistic Infections; Retrospective Studies; Risk Factors

We describe a patient who developed Candida albicans brain abscess associated with prominent vascular invasion following an episode of central venous catheter-related fungemia. The increasing population of immunosuppressed patients and the frequent use of broad-spectrum antimicrobials, corticosteroids, chemotherapeutics, organ transplantation, and prolonged supportive measures are responsible for an increasing incidence of candidal infections. Brain abscess is a rare complication of candidemia but may be expected to become more common as venous catheter-related fungemia is encountered more frequently.

Topics: Amphotericin B; Arterial Occlusive Diseases; Brain; Brain Abscess; Candida albicans; Candidiasis; Carotid Artery Diseases; Carotid Artery, Internal; Catheterization, Central Venous; Cerebral Arteries; Craniotomy; Drug Therapy, Combination; Flucytosine; Fungemia; Humans; Magnetic Resonance Angiography; Male; Middle Aged; Tomography, X-Ray Computed

Topics: Amphotericin B; Brain Abscess; Candidiasis; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; Fungemia; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Tomography, X-Ray Computed

Malassezia furfur sepsis developed in a woman with hyperemesis gravidarum while she was receiving total parenteral nutrition supplemented with lipids. Fever, chills, dyspnea, pleuritic chest pain, and multiple bilateral pulmonary nodular infiltrates were the primary clinical manifestations. Lysis-centrifugation fungal blood cultures supplemented with olive oil grew M furfur. Treatment included removal of the central venous catheter line, discontinuation of the lipid emulsion, and antifungal chemotherapy. Malassezia furfur sepsis complicating total parenteral nutrition may be more common in adults than once suspected. A high index of suspicion is required to diagnose this infection, and the addition of olive oil to the fungal culture medium will provide the necessary growth factors to isolate this fungus.

Topics: Adult; Amphotericin B; Catheterization, Central Venous; Female; Fungemia; Humans; Hyperemesis Gravidarum; Malassezia; Parenteral Nutrition, Total; Pregnancy; Pregnancy Complications, Infectious; Pulmonary Embolism

The in vitro activity of amphotericin B, flucytosine and fluconazole against 95 yeasts causing fungemia in a single institution over the last eight years was determined by a broth macromethod recommended by the National Committee for Clinical Laboratory Standards. All strains were inhibited by amphotericin B concentrations of < or = 1 microgram/ml. With flucytosine in most species the MIC50 was between 0.12 and 0.25 microgram/ml and the MIC90 was between 0.25 and 1 microgram/ml. One exception with flucytosine was Candida krusei, with an MIC50 and MIC90 of 16 micrograms/ml and 32 micrograms/ml, respectively. Overall, 12% of the isolates needed at least 8 micrograms/ml of fluconazole to be inhibited. Fluconazole was very active against Candida albicans, Candida tropicalis and Cryptococcus neoformans, with MIC50 ranging from 0.12 to 0.5 microgram/ml and MIC90 of 1 microgram/ml, and somewhat less active against Candida parapsilosis (MIC50 of 1 microgram/ml and MIC90 of 4 micrograms/ml). Fluconazole exhibited poor in vitro activity against Candida krusei (MIC50 and MIC90 of 64 micrograms/ml) and Torulopsis glabrata (MIC50 of 4 micrograms/ml and MIC90 of 16 micrograms/ml). High MICs of fluconazole were found for four strains of Candida albicans, one with an MIC of 4 micrograms/ml and three (5.7%) with MICs of > or = 16 micrograms/ml. Previous exposure to fluconazole could be demonstrated in two of these strains. Further work must be done in order to determine appropriate breakpoints of antifungal agents, to assess the clinical relevance of azole resistance in yeasts causing bloodstream infections and to identify risk factors for infections with azole-resistant yeasts.

Topics: Amphotericin B; Fluconazole; Flucytosine; Fungemia; Humans; Microbial Sensitivity Tests; Yeasts

Mucormycosis is a rare fungal disease commonly affecting individuals with diabetes mellitus, hematological malignancy, and immune deficiency. Isolated pulmonary mucormycosis is extremely rare. This article reports a case of isolated pulmonary mucormycosis that presented as a solitary cavity infiltrate in a patient with no underlying risk factors.

Topics: Aged; Amphotericin B; Fatal Outcome; Fungemia; Humans; Lung Diseases, Fungal; Male; Mucormycosis; Radiography; Renal Insufficiency; Shock, Septic

To determine the efficacy of short-course (7 to 14 days of therapy after the last positive blood culture) amphotericin B therapy for candidemia in children.. Case series.. Tertiary care university medical center in Virginia.. Thirty patients younger than 17 years of age who had candidemia between 1983 and 1990.. The charts of 30 children with 31 episodes of candidemia were retrospectively reviewed for patient data, dates of positive and negative cultures for Candida from blood and other sites, dates of removal of the intravascular catheters, duration and dosage of amphotericin B administration, and outcome. Eight patients had persistent candidemia and died. Five patients were treated not in accordance with the short-course recommendations. Two had relapses; 1 was cured with catheter removal alone, and 2 were successfully treated with 26 and 30 days of amphotericin B therapy. Eighteen episodes (two episodes in 1 patient) of candidemia were cured using 7 to 14 days of amphotericin B therapy after the last positive blood culture.. Once the bloodstream is sterilized, and there is no other evidence of invasive fungal disease, 7 to 14 additional days of amphotericin B at a dose of 0.5 mg/kg per day seems adequate for treatment of candidemia in children.

Topics: Amphotericin B; Candidiasis; Child; Child, Preschool; Drug Administration Schedule; Fungemia; Humans; Infant; Infant, Newborn; Retrospective Studies; Treatment Outcome

Topics: Amphotericin B; Candidiasis; Catheterization; Fluconazole; Fungemia; Humans

Topics: Amphotericin B; Candidiasis; Fluconazole; Fungemia; Humans

Topics: Amphotericin B; Candidiasis; Catheterization, Central Venous; Fluconazole; Fungemia; Humans

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

Fusarium infection is increasingly reported in immunocompromised patients. The role of central venous catheters as potential portals of entry for Fusarium is possibly underestimated. Four cases of catheter-related fusarial infection in children with acute leukemia or a solid tumor are described. These patients had an excellent response to removal of the central venous catheter and treatment with amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Catheterization, Central Venous; Child; Child, Preschool; Female; Fungemia; Fusarium; Humans; Immunocompromised Host; Male; Neoplasms

The authors report a case of acute renal failure caused by fungal bezoar in the renal pelvis. The patient was successfully treated with bilateral percutaneous nephrostomy drainage. He had been admitted because of necrotizing enterocolitis, at the age of 26 days. Eventually, his bowel was reduced to 40 cm of small intestine, including 5 cm of terminal ileum. Candida sepsis developed during central total parenteral nutrition, at the age of 76 days. Five weeks after the diagnosis of systemic candidiasis, sudden anuria developed, and ultrasonography showed echogenic material in both renal pelvises. Bilateral percutaneous nephrostomy catheters were placed in the renal pelvises, and local irrigation with amphotericin B was performed for 3 weeks. The renal function of the baby was completely recovered, without systemic antifungal treatment.

Topics: Acute Kidney Injury; Amphotericin B; Antifungal Agents; Bezoars; Candidiasis; Catheterization, Central Venous; Fungemia; Humans; Hydronephrosis; Infant, Newborn; Kidney Pelvis; Male; Parenteral Nutrition, Total; Ultrasonography

The use of high dose chemotherapy in the treatment of solid tumors is associated with prolonged neutropenia and, consequently, in some patients, systemic candidiasis. The authors describe their experience with a clinicoradiologic syndrome developing after high dose chemotherapy was administered to patients with breast cancer.. The authors evaluated the clinical and radiologic records of 12 patients in whom hepatic, splenic, or renal candidiasis developed.. Three patients had positive blood cultures for candida tropicalis. One of these patients and two others had fungal organisms identified with special stains of an organ aspirate. Most patients were asymptomatic, and most of them were treated successfully with antifungal agents, although untreated patients also recovered. There were no fatalities due to the candidiasis.. A radiographic syndrome resembling hepatic, splenic, or renal candidiasis is described, which occurred after high dose chemotherapy was administered and autologous bone marrow transplantation was performed on patients with breast cancer. This syndrome has a favorable prognosis. Conclusions as to the more indolent nature of this syndrome cannot be made; however, this topic warrants further investigation.

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Bone Marrow Transplantation; Breast Neoplasms; Candidiasis; Combined Modality Therapy; Female; Fluconazole; Fungemia; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Kidney Diseases; Liver Diseases; Middle Aged; Neutropenia; Retrospective Studies; Splenic Diseases; Syndrome; Tomography, X-Ray Computed; Transplantation, Autologous

Intensive chemotherapy has prolonged survival in cancer patients. Unfortunately it has also predisposed them to unusual infections because of their immunocompromised state. We report a case of fungal septicaemia caused by Geotrichum candidum, an imperfect yeast of low virulence in a young girl with acute lymphoblastic leukaemia. It was successfully treated with amphotericin B. The morphological characteristics of this fungus leading to its identification are described.

Topics: Amphotericin B; Antineoplastic Agents; Child, Preschool; Female; Fungemia; Geotrichosis; Humans; Immunocompromised Host; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Candida; Candidiasis, Oral; Female; Fluconazole; Fungemia; Humans; Recurrence; Zidovudine

Topics: Adult; Amphotericin B; Candidiasis; Fluconazole; Fungemia; Humans; Neutropenia

Topics: Aged; Agranulocytosis; Amphotericin B; Candidiasis; Child; Child, Preschool; Drug Carriers; Fat Emulsions, Intravenous; Female; Fungemia; Humans; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Male

We performed antifungal susceptibility tests with cilofungin (LY121019), amphotericin B, and flucytosine against 38 strains of yeasts from patients with esophagitis or fungemia either before, during, or after treatment with cilofungin. Tests were performed using a macrobroth dilution method similar to that proposed by the National Committee for Clinical Laboratory Standards (M27-P) and two microbroth methods. For cilofungin and amphotericin B, minimum inhibitory concentrations from microbroth tests using Antibiotic Medium 3 (AM3) were systematically lower than results from the other two methods that utilized RPMI-1640 medium (RPMI). AM3 did not provide any greater degree of in vitro correlation with clinical results than did RPMI. We conclude that cilofungin and possibly other congeners of the echinocandin class of antifungal agents can effectively be studied using the proposed National Committee for Clinical Laboratory Standards method.

Topics: Amphotericin B; Candida; Candidiasis; Drug Resistance, Microbial; Echinocandins; Esophagitis; Evaluation Studies as Topic; Flucytosine; Fungemia; Humans; Microbial Sensitivity Tests; Peptides, Cyclic; Prospective Studies

Candida albicans meningitis developed in a 55-year-old diabetic female, 1 year after catheter-associated candidemia. It was characterized by a protracted course, lack of meningeal signs, and the presence of an intradural filling defect within the caudal canal. Complete resolution of this filling defect with antifungal therapy implies that it probably represented an inflammatory mass. The development of meningitis after self-limiting candidemia and similar intradural filling defects have not been reported previously.

Topics: Amphotericin B; Candida albicans; Candidiasis; Catheters, Indwelling; Female; Fluconazole; Fungemia; Humans; Meningitis, Fungal; Middle Aged; Time Factors

Serious infections caused by Torulopsis glabrata, once rarely encountered, have become common over the last 3 decades. The most frequent manifestations of serious fungal infections include septicemia, endocarditis, hepatosplenic infections, and meningitis. We report a case of fungemia and pelvic abscess caused by T glabrata following gynecologic surgery.. A 43-year-old woman developed fever, abdominal pain, and abdominal distention following a total abdominal hysterectomy and right salpingo-oophorectomy. Empirical treatment with broad-spectrum antimicrobial agents was not successful. Three sets of blood cultures were positive for T glabrata, and radiologic investigations revealed pelvic and lesser sac fluid collections. Cultures of the pelvic abscess grew T glabrata. Treatment was changed to amphotericin B, with complete clinical recovery.. Serious T glabrata infections are rare following gynecologic surgery, especially in immunocompetent patients. Given the morbidity and mortality associated with these infections, aggressive treatment with amphotericin B and drainage of abscesses is warranted.

Topics: Abscess; Adult; Amphotericin B; Candidiasis; Female; Fungemia; Humans; Hysterectomy; Pelvis; Postoperative Complications; Uterine Neoplasms

Fungal endocarditis is considered an absolute indication for valve replacement surgery. We describe the successful medical treatment of recurrent Candida parapsilosis candidemia with sequential treatment with amphotericin B and fluconazole in a patient with probable prosthetic valve endocarditis. Because of the presumed effectiveness of amphotericin B and fluconazole in the treatment of this patient, medical therapy should be considered as potentially useful in the treatment of recurrent C parapsilosis fungemia or endocarditis or both.

Topics: Amphotericin B; Candidiasis; Drug Therapy, Combination; Endocarditis; Fluconazole; Fungemia; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Recurrence

A simple, rapid susceptibility test is needed to determine the possible resistance of yeasts to commonly used antifungal agents. The BacT/Alert automated blood culture system was evaluated as one technology for development of such a test. Yeast nitrogen base was used as the growth medium, and amphotericin B was the test antifungal agent. Isolates of various Candida species, Torulopsis glabrata, Saccharomyces cerevisiae, and Cryptococcus neoformans were evaluated. The results suggest that detection of amphotericin B resistance of yeast isolates within 12 to 14 h after inoculation of test medium is possible.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Cross Infection; Culture Media; Evaluation Studies as Topic; Fungemia; Fungi; Humans; Microbial Sensitivity Tests; Mycoses; Saccharomyces cerevisiae

A case of Candida parapsilosis endocarditis observed 16 months after BMT is reported. The patient, a 35-year-old female with CML, suffered from Candida parapsilosis fungemia on day +22 after BMT. In spite of treatment with amphotericin B, fluconazole and catheter withdrawal, the same yeast was isolated > 1 year later from a vegetation on an old rheumatic mitral valve. Although the patient remained in complete cytogenetical and hematological remission, in vitro tests showed reduced phagocytic and chemotactic capacity of neutrophils and monocytes. This case stresses the need of prolonged therapy for patients with candidemia after BMT.

Topics: Adult; Amphotericin B; Bone Marrow Transplantation; Candida; Candidiasis; Endocarditis; Female; Fluconazole; Fungemia; Heart Valve Diseases; Humans; Mitral Valve; Recurrence

Twenty-six cases of candidemia associated with a well-defined urinary tract source were retrospectively identified and reviewed. Urinary tract abnormalities were present in 23 of 26 patients (88%), 19 (73%) of whom had urinary tract obstruction. Nineteen patients had undergone urinary tract procedures before the onset of candidemia. Episodes of candidemia were brief and low-grade in intensity (median duration, 1 day; median colony count, 1.5 cfu/10 mL of blood). Only eight patients (31%) received > or = 500 mg of amphotericin B. There were five in-hospital deaths (19%); two of these deaths were attributed to candidiasis. No late complications of candidemia were documented for the surviving patients. Patients with urologic pathology and candiduria who undergo surgery or manipulation of the urinary tract are at significant risk for candidemia, and further studies should examine the issue of administration of prophylaxis to this group.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Candidiasis; Female; Fungemia; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Treatment Outcome; Urinary Tract; Urinary Tract Infections; Urine; Urography; Urologic Diseases

The incidence of candidemia and its complications, such as endophthalmitis, has measurably increased in recent years. However, the optimal method of treatment of hematogenous candidal infection remains a controversial issue. Traditional therapy with amphotericin B is associated with well-known adverse reactions. Many clinicians therefore prefer to use fluconazole, which is administered orally and is relatively less toxic. We recently observed a patient with candidal sepsis in whom blinding endophthalmitis developed despite aggressive and lengthy therapy with fluconazole. This grave clinical outcome and the data derived from experimental models of ocular candidal infection suggest that empirical usage of fluconazole may not be warranted in cases of disseminated candidiasis potentially complicated by endophthalmitis.

Topics: Adult; Amphotericin B; Candidiasis; Cross Infection; Endophthalmitis; Female; Fluconazole; Fungemia; Humans; Pyelonephritis

Invasive aspergillosis developed in three (5%) of 55 adult liver transplant recipients at our institution. All three of our patients had concomitant candidemia and consumption coagulopathy, and invasive aspergillosis developed while they were receiving therapy with intravenous amphotericin B (0.5 mg/[kg.d]). The simultaneous occurrence of candidemia and invasive aspergillosis in liver transplant recipients may reflect a common defect in the host-defense mechanism against Candida and Aspergillus organisms (i.e., impaired phagocytic and mononuclear macrophage function) and liver disease per se. These three cases suggest that such low-dose intravenous amphotericin B will likely be ineffective if used as antifungal prophylaxis for invasive aspergillosis.

Topics: Adult; Amphotericin B; Aspergillosis; Candidiasis; Disseminated Intravascular Coagulation; Fungemia; Humans; Liver Transplantation; Male; Middle Aged

We report here the second case of Candida utilis infection in humans. The patient was apparently immunocompetent, had no central catheter, and survived an 8-day fungemia. Genomic analysis confirmed the conspecificity of medical and industrial strains of C. utilis and that of the anamorphic yeast C. utilis with the teleomorphic yeast Pichia jadinii.

Topics: Aged; Amphotericin B; Candida; Candidiasis; DNA, Fungal; Fungemia; Humans; Male; Virulence

The objective of this study is to identify prognostic factors affecting mortality in surgical patients with culture-proved fungemia and to examine how amphotericin B affects mortality after controlling for these factors.. The study is based on a retrospective logistic regression analysis of general surgical patients with blood cultures positive for fungi. We analyzed the patients' ages; whether they received triple antibiotics, had diabetes, had malignant neoplasia, received steroids, had concomitant bacteremia, or took antibiotics for greater than 7 days; and total dose of amphotericin B.. The study was carried out at a university-based county hospital.. Analysis of microbiology records for blood cultures that were positive for fungi from November 1987 to January 1992 revealed 63 general surgical patients. Patients with burns and those undergoing organ transplantation were excluded. Forty charts were complete and available for review.. Death was the outcome variable studied.. Stepwise logistic regression analysis of death revealed age to be a risk factor for mortality. Treatment with at least 210 mg of amphotericin B was associated with relative risk of death of 0.055.. Amphotericin B is effective even at low doses at decreasing the mortality in surgical patients with fungemia. On the other hand, increasing age is associated with an increased risk of mortality. Found not to be associated were concomitant bacteremia, concurrent triple antibiotic therapy, malignant neoplasia, and steroid use.

Topics: Age Factors; Aged; Amphotericin B; Aspergillosis; Candidiasis; Female; Fungemia; Histoplasmosis; Humans; Logistic Models; Male; Middle Aged; Postoperative Complications; Prognosis; Regression Analysis; Retrospective Studies; Risk Factors; Survival Analysis

Systemic and gastrointestinal infection was established in infant (15-19 days old) mice after oral-intragastric challenge with Candida albicans. All survivors retained high levels of organisms in the liver, kidney, spleen, stomach and intestine up to the 24th post infection day. These animals with persistent infections were used to study the efficacy of short term antifungal therapy. Drug treatment was initiated on 13th day for a two week period, treatment with fluconazole was compared with amphotericin B, and 5 fluorocytosine. The results suggest that fluconazole is a useful drug in the treatment of gastrointestinal candidiasis.

Topics: Amphotericin B; Animals; Candidiasis; Disease Models, Animal; Fluconazole; Flucytosine; Fungemia; Gastrointestinal Diseases; Mice

Topics: Adult; Amphotericin B; Candidiasis; Female; Fluconazole; Fungemia; Humans

Amphotericin B (Amph-B) is the treatment of choice for systemic fungal infections. The application of high doses is limited due to the high incidence of acute side effects (fever, chills) and organ toxicity (reduction in glomerular filtration rate, renal tubular damage). Amph-B was applied without success in a three months old infant, who suffered from systemic candidiasis. After a change to high doses (3-5 mg/kg/day) of liposomal Amph-B (Amph-lip) rapid improvement of the patient's condition occurred and the pulmonary lesions disappeared during six weeks of treatment (total dose 185.5 mg/kg). Acute side effects or renal function abnormalities did not occur. The reported case indicates that the application of high doses of Amph-lip is an alternative to conventional Amph-B in treatment of systemic fungal infections.

Topics: Amphotericin B; Candidiasis; Cross Infection; Dose-Response Relationship, Drug; Drug Carriers; Female; Fungemia; Humans; Infant; Infusions, Intravenous; Liposomes

Topics: Amphotericin B; Candidiasis; Drug Therapy, Combination; Flucytosine; Fungemia; Humans; Infant, Newborn

Candida krusei has become an increasingly important invasive pathogen, particularly in immunocompromised patients. Previous experimental and clinical experience suggest that C. krusei has a low propensity for hematogenously infecting the eye. We report 10 cases of fungemia due to C. krusei at our institutions, including three cases of endophthalmitis due to C. krusei. Fungemia was associated with nodular skin lesions in all seven patients with neutropenia and occurred despite administration of antifungal prophylaxis or empirical therapy. None of the patients apparently died as a direct result of C. krusei fungemia. Treatment with amphotericin B resulted in resolution of endophthalmitis, although one patient required vitrectomy. Early institution of aggressive therapy with amphotericin B may alter the course and improve the prognosis of C. krusei infection, particularly in immunocompromised patients.

Topics: Aged; Amphotericin B; Candida; Candidiasis; Endophthalmitis; Eye Infections, Fungal; Female; Fungemia; Humans; Male; Middle Aged; Prospective Studies; Retrospective Studies; Skin

We reviewed all 155 episodes of central venous catheter-associated fungemia among inpatients at the National Cancer Institute during a 10-year period. Candida species accounted for 98% of episodes. Fungemia was documented by culture of blood drawn through catheters in 50% of cases and by culture of both catheter-drawn and peripheral blood in 39%; mortality and the rate of dissemination were similar for these two groups. Four management strategies were used: catheter removal, antifungal therapy (with amphotericin B), both, or neither; indications for the use of both modes of treatment included fever, neutropenia, long-term indwelling catheterization, positive cultures of both catheter-drawn and peripheral blood, isolation of Candida tropicalis, and fungal isolation from two or more blood cultures. Disseminated fungal infection was documented in 82% of cases with these features but also in 35% of the less severe cases treated only with catheter removal. In addition, nine (82%) of 11 cases managed only with antifungal therapy had a negative outcome (either death from disseminated infection or the recurrence of fevers and/or fungemia), a finding suggesting that intravascular catheters should be removed in fungemia. Virtually all cases of catheter-associated fungemia in patients with cancer are clinically significant and require prompt therapy with amphotericin B.

Topics: Adolescent; Adult; Aged; Amphotericin B; Candidiasis; Catheterization, Central Venous; Catheters, Indwelling; Chemotherapy, Adjuvant; Child; Child, Preschool; Cross Infection; Female; Fungemia; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Retrospective Studies

Topics: Amphotericin B; Candidiasis; Child, Preschool; Fluconazole; Fungemia; Humans; Male; Risk Factors

A 51-year-old man who was being treated with corticosteroids for chronic extrinsic asthma developed biliary tract sepsis, candidemia, and Candida endophthalmitis with vitreous fluff-ball lesions in both eyes. Extensive vitreous fibrosis and retinal detachment with loss of useful vision occurred in his left eye, which had a vitreous biopsy. Useful vision was maintained in his right eye with two full courses of systemic amphotericin B, 5-flucytosine, and a cataract extraction. Encapsulated Candida organisms remained in the vitreous of his right eye at the time of death. Useful vision can be preserved without aggressive vitreous surgery and intravitreal anti-fungal agents in eyes with intravitreal Candida albicans.

Topics: Amphotericin B; Candidiasis; Cataract Extraction; Endophthalmitis; Eye Infections, Fungal; Fibrosis; Flucytosine; Fungemia; Humans; Male; Middle Aged

Topics: Abdomen; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Fungemia; Pelvis