amphotericin-b and Candidemia

Candidemia is the fourth most common nosocomial bloodstream infection. Endocarditis from candidemia is a rare but possibly fatal complication. The efficacy of amphotericin and echinocandins for induction and azoles for suppression has been well studied. Source control of infection, including removal of foreign bodies, remains the cornerstone for the success of any antifungal therapy.. We are describing a case of a 63-years old patient with multiple comorbidities who developed candidemia secondary to Candida albicans. The prospect of curing the fungemia was made difficult by prosthetic devices, including prosthetic heart valves, intracardiac defibrillator, and inferior vena filter, which could not be extracted due to poor cardiovascular status and higher postoperative mortality risk. Combination therapy with amphotericin and 5-Flucytosine (5FC) was used with the first recurrence. Suppression with fluconazole was contraindicated due to prolonged corrected QT (QTc) interval. Isavuconazole was employed for chronic lifelong suppression.. Retaining prosthetics in higher surgical risk patients presents us with unique clinical and pharmacological challenges regarding breakthrough infections, drug interaction, and side effects from prolonged suppressive therapies.

Topics: Amphotericin B; Candida albicans; Candidemia; Drug-Related Side Effects and Adverse Reactions; Endocarditis; Humans; Middle Aged

Regardless of the available antifungals, intraabdominal candidiasis (IAC) mortality continues to be high and represents a challenge for clinicians.. This opinion paper discusses alternative antifungal options for treating IAC. This clinical entity should be addressed separately from candidemia due to the peculiarity of the required penetration of antifungals into the peritoneal cavity. Intraabdominal concentrations may be further restricted in critically ill patients where pathophysiological facts alter normal drug distribution. Echinocandins are recommended as first-line treatment in guidelines for invasive candidiasis. However, considering published data, our pharmacodynamic analysis suggests the required increase of doses, postulated by some authors, to attain adequate pharmacokinetic (PK) levels in peritoneal fluid. Given the limited evidence in the literature on PK/PD-based treatments of IAC, an algorithm is proposed to guide antifungal treatment. Liposomal amphotericin B is advocated as first-line therapy in patients with sepsis/septic shock presenting candidemia or endophthalmitis, or with prior exposure to echinocandins and/or fluconazole, or with infections by Candida glabrata. Other situations and alternatives, such as new compounds or combination therapy, are also analysed.. There is a critical need for more robust clinical trials, studies examining patient heterogeneity and surveillance of antifungal resistance to enhance patient care and optimise treatment outcomes. Such evidence will help refine the existing guidelines and contribute to a more personalised and effective approach to treating this serious medical condition. Meanwhile, it is suggested to broaden the consideration of other options, such as liposomal amphotericin B, as first-line treatment until the results of the fungogram are available and antifungal stewardship could be implemented to prevent the development of resistance.

Topics: Antifungal Agents; Candidemia; Candidiasis, Invasive; Echinocandins; Humans

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

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

Because exclusive use of echinocandins can induce the drug-resistant strains, appropriate use of azoles and polyenes is still necessary in the treatment of candidemia. In this study, we conducted a meta-analysis of randomized controlled trials regarding the efficacy and safety of azole and polyene antifungals in the treatment of candidemia. MEDLINE and the Cochrane Register of Controlled Trials were used as reference databases, and papers published up to June 10, 2019 were searched. The search results were carefully scrutinized, duplicate references were removed, and the study was ultimately carried out using three reports. Among azole antifungals, fluconazole and voriconazole were extracted, however; only conventional amphotericin B (AMPH-B) was extracted among polyene antifungals. Treatment successes with the use of azoles and AMPH-B were compared, and findings showed that AMPH-B was significantly superior (RR = 0.90, 95% CI 0.82-1.00, p = 0.04). However, there was no significant difference in mortality (RR = 0.87, 95% CI 0.72-1.07, p = 0.19). Analysis of adverse events showed that renal disorders were significantly less common with azoles than with AMPH-B (RR = 0.26, 95% CI 0.10-0.68, p = 0.006). In conclusion, AMPH-B were superior to azoles in terms of efficacy, but had a risk of causing renal disorders.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candidemia; Echinocandins; Humans; Randomized Controlled Trials as Topic

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

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

Ascomycetous yeast species belonging to the subphylum Saccharomycotina (Ascomycota, Fungi) may cause a variety of pathologies in humans. Candida albicans accounts for almost half of candidemia cases but the emergence of uncommon yeasts in the clinical setting is increasing. Here, we highlight the epidemiology of Saccharomycotina budding yeasts causing bloodstream infections, address antifungal susceptibility patterns and unravel how the latter corresponds to their phylogenetic relationship. Only studies applying Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and/or sequence-based identification methods were considered. A ribosomal DNA-based phylogeny was used to present phylogenetic relationships of yeasts pathogens and their close relatives and to show how the antifungal susceptibility patterns for amphotericin B and azole drugs correlate with the clades found. Candida albicans was still the leading cause of yeast-related sepsis, but 22 other Saccharomycotina yeast species were also identified as a common cause of sepsis based on the literature. Similar minimum inhibitory concentration (MIC) values are found between phylogenetically closely related species and appear to be clade-specific to a large extent. This demonstrates that phylogeny may serve as a first guidance for treatment of emerging yeasts with uncommon susceptibility patterns due to intrinsic resistance.

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Azoles; Candida; Candidemia; DNA, Ribosomal; Humans; Microbial Sensitivity Tests; Phylogeny; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Invasive candidiasis is the most common fungal infection affecting critically ill adults. International guidelines provide differing recommendations for first-line antifungal therapy, with echinocandins considered first-line in the majority. Amphotericin B has broad activity and low minimum inhibitory concentration resistance patterns across most Candida species and guidance away from its use should be supported by the available evidence. Areas Covered: A systematic literature review was conducted from August to September 2017 to determine whether treatment with echinocandins or other available drugs, namely voriconazole, confers a therapeutic or survival benefit over amphotericin B in critically ill adults with invasive candidiasis. Inclusion criteria were: (1) studies describing critically ill adults with invasive candidiasis, (2) studies describing therapeutic benefit or survival as an outcome, and (3) studies comparing amphotericin B, deoxycholate or lipid preparations, with any newer antifungal agent. Eight studies were included in the final review, incorporating 2352 unique patients. No difference in treatment efficacy or mortality outcomes in critically ill patients with invasive candidiasis receiving an amphotericin B formulation compared with those receiving an echinocandin or voriconazole was shown. Expert Commentary: We conclude that in the existing literature, there is no evidence that choice between echinocandins, voriconazole, or amphotericin B formulations as first-line therapy for critically ill adults with invasive candidiasis is associated with a therapeutic or survival benefit. Clinicians must therefore consider other factors in the selection of first-line therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidemia; Candidiasis, Invasive; Critical Illness; Humans; Microbial Sensitivity Tests; Practice Guidelines as Topic

Bloodstream infection with Candida species is not uncommon in the intensive care unit setting and has the potential to distribute organisms to many different organ systems causing secondary infections, such as endophthalmitis, osteomyelitis, and endocarditis. In some patients, these types of infections become manifested shortly after the episode of candidemia. In others, especially vertebral osteomyelitis, weeks pass before the diagnosis is entertained. Endophthalmitis should be sought by a retinal examination in all patients early after an episode of candidemia. Both osteomyelitis and endocarditis are less common complications of candidemia than endophthalmitis. In patients who manifest symptoms or signs suggesting these infections, magnetic resonance imaging and transesophageal echocardiography, respectively, are extremely helpful diagnostic tests. Newer approaches to the treatment of these infections allow the use of better tolerated, safer antifungal agents. Endophthalmitis is often treated with fluconazole or voriconazole, and the echinocandins are increasingly used, instead of amphotericin B, as initial therapy for osteomyelitis and endocarditis before step-down therapy to oral azole agents.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidemia; Echinocandins; Echocardiography; Endocarditis; Endophthalmitis; Fluconazole; Humans; Intensive Care Units; Magnetic Resonance Imaging; Osteomyelitis; Voriconazole

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

In our part of the world invasive fungal infections include invasive yeast infections with Candida as the absolutely dominating pathogen and invasive mould infections with Aspergillus as the main organism. Yeasts are part of our normal micro-flora and invasive infections arise only when barrier leakage or impaired immune function occurs. On the contrary, moulds are ubiquitous in the nature and environment and their conidia inhaled at a daily basis. Hence invasive mould infections typically arise from the airways whereas invasive yeast infections typically enter the bloodstream causing fungaemia. Candida is by far the most common fungal blood stream pathogen; hence this genus has been the main focus of this thesis. As neither the Danish epidemiology nor the susceptibility of fungal pathogens was well described when we initiated our studies we initially wanted to be able to include animal models in our work. Therefore, a comprehensive animal study was undertaken comparing the virulence in a haematogenous mouse model of eight different Candida species including the five most common ones in human infections (C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis and in addition three rarer species C. guilliermondii, C. lusitaniae and C. kefyr). We found remarkable differences in the virulence among these species and were able to group the species according to decreasing virulence in three groups I: C. albicans and C. tropicalis, II: C. glabrata, C. lusitaniae and C. kefyr, and III: C. krusei, C. parapsilosis and C. guilliermondii. Apart from being necessary for our subsequent animal experiments exploring in vivo antifungal susceptibility, these findings also helped us understand at least part of the reason for the differences in the epidemiology and the pitfalls associated with the establishment of genus rather than species specific breakpoints. In example, it was less surprising that C. albicans has been the dominant pathogen and associated with a significantly higher mortality than C. parapsilosis and that C. glabrata and C. krusei mainly emerged in the post fluconazole era and in settings with azole selection pressure. Moreover, it was less surprising that infections due to mutant C. albicans isolates with echinocandin MICs of 1-2 mg/l were not good targets for the echinocandins despite the fact that the outcome for infections involving wild type C. parapsilosis for which similar echinocandin MICs were similar was not inferior. This last ob

Topics: Amphotericin B; Antifungal Agents; Candida; Candidemia; Denmark; Echinocandins; Fluconazole; Humans; Incidence; Microbial Sensitivity Tests

Candida famata (also known as Debaryomyces hansenii and Torulopsis candida) is a commensal yeast found in cheese, dairy products and the environment. C. famata accounts for 0.2%-2% of invasive candidiasis. The purpose of this study was to provide an overview of the treatment of C. famata bloodstream infections.. The clinical course of two hospitalized patients who developed C. famata fungaemia within 2 weeks of each other was summarized along with available data regarding in vitro susceptibility patterns, genotyping and clinical outcomes of these cases compared with the published literature.. C. famata appears to exhibit reduced susceptibility to echinocandins and azoles, particularly in the setting of prior antifungal exposure. The removal of indwelling central venous catheters and prompt initiation of therapy with liposomal amphotericin B is recommended for successful treatment of C. famata fungaemia, particularly in immunocompromised patients. These cases also help provide justification for routine antifungal susceptibility testing in patients with candidaemia to guide optimal antifungal therapy.

Topics: Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidemia; Catheter-Related Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Treatment Outcome

In 2009 the Infectious Diseases Society of America reviewed the guidelines on the treatment of candidemia in non-neutropenic patients. In this document the preferred treatment was either fluconazole or an echinocandin. Amphotericin-B formulations were considered an alternative. However, careful assessment of published data showed similar efficacy between these drugs.

Topics: Adult; Amphotericin B; Animals; Antifungal Agents; Candidemia; Echinocandins; Fluconazole; Fungal Proteins; Humans; Kidney Diseases; Neutropenia; Practice Guidelines as Topic; Treatment Outcome

There are a variety of diseases, from local mucous membrane infections to invasive systemic infections, that are caused by Candida species. As a causative agent, Candida albicans is the most common; however, the other Candida species can also cause the same clinical syndromes. Most invasive fungal infections in children occur in the hospital setting. Candidemia is a serious condition associated with high morbidity and mortality and increased healthcare costs in pediatric patients. Children at the highest risk are those with prolonged intensive care unit stays, reduced immune function, recent surgery, prior bacterial infection, prior use of antibiotics and/or corticosteroids and other immunosuppressive agents, as well as use of a central venous catheter, total parenteral nutrition, mechanical ventilation and dialysis. Positive blood culture is the gold standard of candidemia; it should not be accepted as contamination or colonization in children with an intravascular catheter. However, in oropharyngeal or vulvovaginal candidiasis, culture of lesions is rarely indicated unless the disease is recalcitrant or recurrent. Recovery of Candida from the sputum should usually be considered as colonization and should not be treated with antifungal therapy. Antigen and antibody detecting tests are evaluated in invasive Candida infections; however, there are no published results in children, and their roles in diagnosis are also unclear. For the therapy of invasive Candida infections in non-neutropenic patients, fluconazole or an echinocandin is usually recommended. Alternatively, amphotericin B deoxycholate or lipid formulations of amphotericin B can also be used. The recommended therapy of Candida meningitis is amphotericin B combined with flucytosine. The combination therapy for Candida infections is usually not indicated. Prophylaxis in non-neonatal, immunocompetent children is not recommended.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidemia; Catheter-Related Infections; Child; Cross Infection; Deoxycholic Acid; Drug Combinations; Echinocandins; Fluconazole; Flucytosine; Humans; Infant, Newborn; Intensive Care Units; Leukocyte Count; Mycological Typing Techniques; Neutrophils; Survival Rate; United States

Ocular candidiasis is a major complication of candidemia. The incidence, risk factors, and outcome of eye involvement during candidemia are largely unknown. We prospectively studied the ocular manifestations of candidemia in a large, worldwide, randomized multicenter trial that compared voriconazole with amphotericin B followed by fluconazole for the treatment of candidemia.. Nonneutropenic patients with blood cultures positive for Candida species were assigned treatment with voriconazole or with amphotericin B followed by fluconazole in a randomized 2:1 ratio. Dilated fundoscopy was performed in each patient at baseline, on day 7, at 2 and 6 weeks after the end of treatment (EOT), and, if clinically indicated, at 12 weeks after EOT.. Of 370 patients, 49 had findings consistent with the diagnosis of ocular candidiasis at baseline, and an additional 11 patients developed abnormalities during treatment, totaling 60 patients with eye involvement (16%). Of these patients, probable Candida eye infection was diagnosed in 40 patients (6 with endophthalmitis, 34 with chorioretinitis), and possible Candida eye infection in 20 (all with chorioretinitis). The duration of candidemia was significantly longer in patients with ocular candidiasis (median, 4 days; range, 1-18 days) compared with patients without ocular involvement (median, 3 days; range 1-26 days; log rank, P = .026). Therapy with either voriconazole (44 cases) or amphotericin B followed by fluconazole (16 cases) was successful in 65% of patients; outcome was not evaluable in 32% and was unfavorable in 3%.. Ocular involvement occurred in 16% of patients with candidemia; however, endophthalmitis was uncommon (1.6%). Treatment with either voriconazole or amphotericin B followed by fluconazole was successful for ocular candidiasis in most cases with follow-up.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidemia; Endophthalmitis; Eye Infections, Fungal; Female; Fluconazole; Humans; Incidence; Male; Middle Aged; Prospective Studies; Pyrimidines; Risk Factors; Triazoles; Voriconazole; Young Adult

Biofilm formation causes virulence and resistance in Candida albicans. However, little is known about breakthrough candidemia isolates. We evaluated the antifungal activity of fluconazole, anidulafungin, deoxycholate amphotericin B (dAMB), and amphotericin B lipid complex (ABLC) against biofilms of C. albicans isolated from patients with breakthrough candidemia.. The present study used strains of C. albicans isolated from breakthrough and non-breakthrough candidemia patients (control group). The susceptibility of planktonic cells to amphotericin B, anidulafungin, and fluconazole was determined by broth microdilution. Antifungal activity in sessile cells was evaluated using the minimum biofilm eradication concentration (MBEC), metabolic activity was estimated by reducing MTT, and biomass was estimated using crystal violet retention.. The planktonic strains were susceptible to amphotericin B, anidulafungin, and fluconazole, with minimum inhibitory concentrations of 1, ≤0.03, and 2mg/L, respectively. However, fluconazole and anidulafungin did not exert an antifungal effect on biofilms. Additionally, dAMB and ABCL reduced the metabolic activity and biomass. However, eradication was only achieved using 16mg/L dAMB. C. albicans isolates of breakthrough candidemia exhibited strong biofilm production, and the in vitro activity of available therapeutic options was poor.. In the present study, only dAMB and ABCL exhibited antibiofilm effects against sessile breakthrough candidemia isolates.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Biofilms; Candida; Candida albicans; Candidemia; Deoxycholic Acid; Fluconazole; Humans

Candidemia and other forms of invasive candidiasis (C/IC) are serious conditions, especially for immunosuppressed individuals with prolonged hospitalization in intensive care units (ICU). This study analyzed the incremental cost-effectiveness and budgetary impact (BI) of treatment for IC with anidulafungin compared to amphotericin B lipid complex (ABLC) and amphotericin B deoxycholate (ABD) or conventional amphotericin B (CAB), in the Brazilian Unified Health System (SUS). A decision model was conducted with a time horizon of two weeks from the perspective of SUS. The primary effectiveness endpoints were survival and treatment response rate. All patients were followed up until successful therapy or death. BI analysis was performed based on the measured demand method. A five-year time horizon was adopted based on the number of hospitalizations (per 1,000 hospitalizations). For effectiveness measured in the successful response rate (SRR), anidulafungin dominated the ABLC and ABD formulations. In the results of the analysis with the effectiveness measured according to survival, anidulafungin had a better cost-effectiveness ratio (R$988.26/survival) compared to ABD (R$16,359.50/survival). The BI estimate related to the incorporation of anidulafungin suggests savings of approximately 148 million reais in 5 years when comparing it to ABD. The economic evaluation of anidulafungin and its comparators found it to be cost-effective. The consensus of international scientific societies recommends it as a first-line drug for IC, and its incorporation by SUS would be important.

Topics: Anidulafungin; Brazil; Candidemia; Candidiasis, Invasive; Cost-Effectiveness Analysis; Humans

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

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

Data on persistent candidemia (PC), a recognized complication of candidemia, are lacking in China. This study aimed to investigate the clinical characteristics and risk factors for the mortality of PC among adults in China.. This 6-year retrospective study analyzed the prevalence, species distribution, antifungal susceptibility, risk factors, and patient mortality of PC among adults in three regional tertiary teaching hospitals in China from 2016 to 2021. We collected electronic laboratory records data of PC and non-PC patients and used the Student test or Mann-Whitney U test for a retrospective study. Logistic regression was used to identify risk factors associated with persistent candidemia.. The definition of PC was fulfilled by 36 patients (13.7%, 36/263). The mean age of the patients was 59.9 years (60 years for patients with PC; 59.8 years for those with non-PC; P > 0.05) and 131 (60.1%) were men [16 with PC (44.4%), 115 with non-PC (63.2%), P < 0.05]. The mean annual incidence was 0.15/1000 admissions (including PC 0.03/1000 admissions vs. non-PC 0.12/1000 admissions, P < 0.05). Candida parapsilosis (14/36, 38.9%) and Candida albicans (81/182, 44.5%) were the predominant pathogens in patients with PC and non-PC, respectively. Most isolates were susceptible to flucytosine (99.0%) and amphotericin B (99.5%), and the activity of antifungal agents against Candida species was not statistically significantly different between patients with PC and non-PC (P > 0.05). The 30-day mortality rate was 20.2% (16.7% with PC vs. 20.9% with non-PC, P > 0.05). Multivariable regression analysis showed that use of broad-spectrum antibiotics (odds ratio (OR), 5.925; 95% confidence interval (CI), 1.886-18.616, P = 0.002), fluconazole (OR, 3.389; 95% CI, 1.302-8.820, P = 0.012) and C. parapsilosis infection (OR, 6.143; 95% CI, 2.093-18.031, P = 0.001) were independent predictors of PC, sex (male) (OR, 0.199; 95% CI, 0.077-0.518, P = 0.001) was the protective factor for PC. Respiratory dysfunction (OR, 5.763; 95% CI, 1.592-20.864, P = 0.008) and length of hospital stay(OR, 0.925; 95% CI, 0.880-0.973, P = 0.002) were independent predictors of 30-day mortality in patients with non-PC. C. tropicalis bloodstream infection (OR, 12.642; 95% CI, 1.059-150.951; P = 0.045) was an independent predictor of 30-day mortality in patients with PC.. The epidemiological data of patients with PC and non-PC were different in the distribution of Candida species, the mean annual incidence and independent predictors of 30-day mortality. Flucytosine and amphotericin B could be used as first-choice drugs in the presence of PC infections.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candida parapsilosis; Candida tropicalis; Candidemia; China; Female; Flucytosine; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Risk Factors

Candida auris is an emerging yeast pathogen that can cause invasive infections, particularly candidemia, in healthcare settings. Candida auris is characterized by resistance to multiple classes of antifungal drugs and high mortality.. To describe the risk factors, clinical characteristics, antifungal susceptibility pattern and outcomes of Candida auris blood stream infection.. We conducted a retrospective review of electronic medical records of C. auris fungemia cases in the facilities under Hamad Medical corporation, Qatar from 1/11/2018 to 31/7/2021. Demographic data, risk factors, antibiogram and 30-day outcome are described.. We identified 36 patients with C. auris fungemia. Most of the patients were in intensive care unit following severe COVID-19 pneumonia and had received steroids and broad-spectrum antibiotics. Most cases were central line related. Over 90% of isolates were non-susceptible to fluconazole, while amphotericin B resistance reached 85%. Factors associated with high mortality included initial SOFA score of 9 or above and absence of source control.. Our study reveals a concerning 41.6% mortality rate within 30 days of C. auris candidemia. Furthermore, the prevalence of amphotericin B resistance in Qatar exceeds what has been reported in the literature necessitating further exploration. Echinocandins retains nearly 100% susceptibility and should be prioritized as the treatment of choice. These findings emphasize the need for vigilant monitoring and appropriate management strategies to combat C. auris infections and improve patient outcomes.

Topics: Amphotericin B; Antifungal Agents; Candida auris; Candidemia; COVID-19; Humans; Microbial Sensitivity Tests; Qatar

The increasing incidence of candidemia and the emergence of drug-resistant Candida species are major concerns worldwide. Therefore, long-term surveillance studies are required. Here, we provide one of the largest longitudinal overviews of the trends in the prevalence of Candida species using national data of 57 001 candidemia isolates obtained from > 2000 hospitals for the 2010-2019 period in the Japan Nosocomial Infections Surveillance database. The proportion of Candida species, except Candida krusei and Candida guilliermondii, was almost the same during the study period. The proportion of C. guilliermondii surpassed that of C. krusei in 2014. The incidence of candidemia due to C. albicans (P < 0.0001), C. parapsilosis (P = 0.0002), and C. tropicalis (P < 0.0001) have decreased significantly over this period. Azole susceptibility of C. tropicalis was low, with 17.8% of isolates resistant to fluconazole and 13.5% resistant to voriconazole. The micafungin susceptibility of C. glabrata was low, with 8.0% of isolates showing resistance. The resistance rate of C. krusei toward amphotericin B fluctuated considerably (between 3.2% and 35.7%) over this period. The incidence rate of candidemia caused by C. parapsilosis and C. guilliermondii in hospitals responsible for bone marrow transplantation was significantly higher than that in other hospitals. Overall, our study suggests that in Japan, the species distribution of Candida was almost the same in this period and similar to that reported in North America and Europe. A relatively high resistance to azoles and micafungin was observed in C. glabrata, C. tropicalis, and C. krusei isolates, which require continued surveillance.. This study verifies that the proportion of Candida species in Japan was almost the same from 2010–2019. A relatively higher resistance to azoles and micafungin was observed for C. glabrata, C. tropicalis, and C. krusei isolates.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidemia; Drug Resistance, Fungal; Fluconazole; Humans; Japan; Micafungin; Microbial Sensitivity Tests; Voriconazole

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

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

Invasive candidiasis and/or candidemia (IC/C) is a common fungal infection leading to significant health and economic losses worldwide. Caspofungin was shown to be more effective than fluconazole in treating inpatients with IC/C. However, cost-effectiveness of caspofungin for treating IC/C in Ethiopia remains unknown. We aimed to assess the cost-utility of caspofungin compared to fluconazole-initiated therapies as primary treatment of IC/C in Ethiopia.. A Markov cohort model was developed to compare the cost-utility of caspofungin versus fluconazole antifungal agents as first-line treatment for adult inpatients with IC/C from the Ethiopian health system perspective. Treatment outcome was categorized as either a clinical success or failure, with clinical failure being switched to a different antifungal medication. Liposomal amphotericin B (L-AmB) was used as a rescue agent for patients who had failed caspofungin treatment, while caspofungin or L-AmB were used for patients who had failed fluconazole treatment. Primary outcomes were expected quality-adjusted life years (QALYs), costs (US$2021), and the incremental cost-utility ratio (ICUR). These QALYs and costs were discounted at 3% annually. Cost data was obtained from Addis Ababa hospitals while locally unavailable data were derived from the literature. Cost-effectiveness was assessed against the recommended threshold of 50% of Ethiopia's gross domestic product/capita (i.e.,US$476). Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the findings.. In the base-case analysis, treatment of IC/C with caspofungin as first-line treatment resulted in better health outcomes (12.86 QALYs) but higher costs (US$7,714) compared to fluconazole-initiated treatment followed by caspofungin (12.30 QALYs; US$3,217) or L-AmB (10.92 QALYs; US$2,781) as second-line treatment. Caspofungin as primary treatment for IC/C was not cost-effective when compared to fluconazole-initiated therapies. Fluconazole-initiated treatment followed by caspofungin was cost-effective for the treatment of IC/C compared to fluconazole with L-AmB as second-line treatment, at US$316/QALY gained. Our findings were sensitive to medication costs, drug effectiveness, infection recurrence, and infection-related mortality rates. At a cost-effectiveness threshold of US$476/QALY, treating IC/C patient with fluconazole-initiated treatment followed by caspofungin was more likely to be cost-effective in 67.2% of simulations.. Our study showed that the use of caspofungin as primary treatment for IC/C in Ethiopia was not cost-effective when compared with fluconazole-initiated treatment alternatives. The findings supported the use of fluconazole-initiated therapy with caspofungin as a second-line treatment for patients with IC/C in Ethiopia.

Topics: Adult; Antifungal Agents; Candidemia; Candidiasis, Invasive; Caspofungin; Cost-Benefit Analysis; Echinocandins; Ethiopia; Fluconazole; Humans; Lipopeptides

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Candida glabrata; Candidemia; Caspofungin; Cross-Sectional Studies; Drug Resistance, Fungal; Fluconazole; Humans; Micafungin; Pakistan; Retrospective Studies; Tertiary Care Centers

Candida bloodstream infection continues to be a significant cause of mortality in premature infants. Amphotericin B has been recommended as the primary treatment; however, its use is limited due to drug-induced nephrotoxicity and amphotericin B-resistant candidemia.. The gestational age was 29 (+6) weeks, and birth weight was 1760 g.. The infant was diagnosed with Candida parapsilosis bloodstream infection.. Fluconazole, 12 mg/kg/day, combined with caspofungin (loading dose 3 mg/kg, at a maintenance dose of 2 mg/kg every 24 h) therapy was administered to premature infant with Candida bloodstream infection. When fluconazole or caspofungin was used to treat Candida bloodstream infection in preterm infants, the blood cultures of the infant remained positive for Candida parapsilosis.. All persistent candidemia resolved on fluconazole combined with caspofungin therapy. There were no adverse effects, hepatotoxicity, nephrotoxicity, anemia, or thrombocytopenia.. Fluconazole combined with caspofungin successfully treated Candida bloodstream infection in premature infants at 29 + 6 weeks' gestational age, but large-scale clinical trials are required.

Topics: Amphotericin B; Antifungal Agents; Candida parapsilosis; Candidemia; Caspofungin; Female; Fluconazole; Humans; Infant, Newborn; Infant, Premature; Male; Microbial Sensitivity Tests; Treatment Outcome

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

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

Amphotericin B (AmB) is a very effective antifungal agent, and resistance in clinical isolates is rare. However, clinical treatment with AmB is often associated with severe side effects. Reducing the administration dose of AmB by combining it with other agents is a promising strategy to minimize this toxicity. In this study, we screened a small compound library and observed that the anti-obesity drug rimonabant exhibited synergistic antifungal action with AmB against Candida species and Cryptococcus neoformans. Moreover, the combination of AmB and rimonabant exhibited synergistic or additive effects against Candida albicans biofilm formation and cell viability in preformed biofilms. The effects of this combination were further confirmed in vivo using a murine systemic infection model. Exploration of the mechanism of synergy revealed that rimonabant enhances the fungicidal activity of AmB by increasing cellular oxidative stress and cell membrane permeability. These findings provide a foundation for the possible development of AmB-rimonabant polytherapies for fungal infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Biofilms; Candida albicans; Candidemia; Cell Membrane Permeability; Cryptococcosis; Cryptococcus neoformans; Drug Synergism; Fungi; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Oxidative Stress; Rimonabant; Small Molecule Libraries

Candida auris is an emerging, multidrug-resistant yeast transmitted in healthcare settings. Conventional methods of speciation are unable to identify C. auris to species level. Three methods, namely VITEK® MS v.3.0, VITEK®2 and target sequencing of the internal transcribed spacer (ITS) region and 28S rRNA gene, were evaluated. Antifungal susceptibility testing (AFST) was also performed, and risk factors for acquisition of C. auris candidaemia were studied.. Between November 2016 and November 2017, 203 Candida spp. were isolated from blood cultures, of which 11 isolates that were unidentifiable by conventional methods were further tested by VITEK® MS v.3.0 and VITEK®2 and were confirmed by sequencing. AFST was carried out on all 11 isolates by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Clinical and epidemiological data of all patients retrieved from electronic patient records were reviewed.. Of the 11 isolates identified as C. auris both by ITS and 28S rRNA sequencing, VITEK®2 identified only 5 as C. auris and VITEK® MS v.3.0 was not able to identify any of them as C. auris. Ten isolates (91%) were resistant to fluconazole, whereas all isolates were susceptible to amphotericin B and caspofungin.. Candida auris can be misidentified in routine microbiology laboratories. Sequencing remains the gold standard if commercial identification systems are not updated.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidemia; Humans; India

With improved and prolonged survival of very and extremely low birth weight infants, invasive fungal infection has emerged as an important concern in the neonatal intensive care units. Candidiasis is the third leading cause of late onset sepsis in these neonates and is associated with 20-30% mortality. Extreme prematurity, central venous catheters, prolonged antibiotic exposure, parenteral nutrition are important risk factors. Various forms of cutaneous manifestations of candidiasis have been described ranging from local diaper dermatitis and oral thrush to widespread erosive and ulcerative lesions with extensive crusting in invasive fungal dermatitis. We report a series of four cases with cutaneous hyperpigmentation as manifestation of systemic candidiasis.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candidemia; Candidiasis, Invasive; Female; Humans; Hyperpigmentation; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Male; Neonatal Sepsis

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

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

To determine the prevalence of Candida auris candidaemia in our ICU patients and its molecular epidemiology.. A prospective observational study was conducted on candidaemia in our ICU patients over 18 months during 2016-2017. Demographics, underlying disease, risk factors, antifungal therapy and outcome were studied. Risk factors of C. auris and non-auris candidaemia were compared.. During the study period, among 108 candidaemia cases recorded, the incidence was 6.75/1000 ICU bed days. C. auris topped the list (n = 42, 39.9%), followed by C. tropicalis (34.3%), and C. parapsilosis (15.7%). On bivariate analysis prior antibiotic therapy, long central line days, mechanical ventilation and length of ICU stay were significant risk factors for C. auris candidaemia compared to non-auris candidaemia. Multivariate analysis showed underlying respiratory and neurological diseases as significantly associated with risk of C. auris candidaemia. Fluconazole, amphotericin B, and caspofungin resistance were noted in 97.0%, 93.7% and 3% of C. auris isolates respectively.. Longer duration of central line days, prior antibiotic use, mechanical ventilation and prolonged ICU stay were important risk factors associated with C. auris candidaemia along with underlying respiratory or neurological disease. The isolates are non-clonal in origin, but they belong to a single clade.

Topics: Adult; Aged; Amphotericin B; Amplified Fragment Length Polymorphism Analysis; Antifungal Agents; Candida; Candidemia; Female; Fluconazole; Humans; Incidence; Intensive Care Units; Length of Stay; Male; Middle Aged; Molecular Typing; Phylogeny; Prevalence; Prospective Studies; Respiration, Artificial; Risk Factors; Treatment Outcome

Although antimicrobial stewardship programmes are one of the highest priorities in healthcare systems and many articles have been published, few refer to the implementation of antifungal stewardship and highlight specific points on which efforts should be focused.. To assess the percentage of patients with confirmed candidaemia in whom de-escalation was conducted, and the economic impact of step-down or step-up antifungal therapy. Additionally, we attempted to estimate the potential increase in drug minimum inhibitory concentrations or to detect resistant strains of. We selected, retrospectively, patients who had received systemic antifungal therapy between 2011 and 2016 for documented candidaemia. Statistical analysis and diagrams were used to assess the results.. Of 157 patients with confirmed candidaemia, 58 received azoles, 74 echinocandinsand 18 liposomal amphotericin B for empirical therapy. 51 patients were eligible to step-down to fluconazole but only 23 patients did so. Furthermore, in nine patients unjustified step-up from fluconazole to echinocandins or liposomal amphotericin B was carried out. The additional cost incurred bythe healthcare system due to high prices of echinocandins and liposomal amphotericin B in comparison with fluconazole was€211 837. Interestingly, it was found that one strain of. The presence of a multidisciplinary team, including an infection control specialist and a clinical pharmacist, would limit the prescription of advanced antifungal agents as empirical therapy. Moreover, this team would control the de-escalation process-where applicable-leading to a reduction in costs and, probably, a decrease in the emergence of resistant

Topics: Amphotericin B; Antifungal Agents; Candidemia; Drug Resistance, Fungal; Drug Utilization Review; Echinocandins; Humans; Microbial Sensitivity Tests; Retrospective Studies

This study aimed to describe the effect of initial antifungal therapy on patient mortality and to detail the current distribution and resistance patterns of Candida spp. among patients with candidaemia. A prospective observational study was performed among consecutive patients with candidaemia from 10 Turkish medical centres between January 2015 and November 2018. The primary outcome was 10-day mortality. Species were identified using MALDI-TOF/MS. A total of 342 patients with candidaemia were included, of which 175 (51.2%) were male and 68 (19.9%) were aged <18 years. The most common species were Candida albicans (47.4%), Candida parapsilosis (26.6%), Candida tropicalis (9.6%) and Candida glabrata (7.6%). Among all Candida spp., the 10-day case fatality rate (CFR) was 32.2%. The CFR was highest in patients with C. albicans (57.3%) and lowest in patients with C. parapsilosis (21.8%). The resistance rate to fluconazole was 13% in C. parapsilosis, with no significant effect on mortality. No resistance to echinocandins was detected. In the multivariate analysis, being in the ICU [OR = 2.1 (95% CI 1.32-3.57); P = 0.002], renal failure [OR = 2.4 (1.41-3.97); P = 0.001], total parenteral nutrition [OR = 2 (1.22-3.47); P = 0.006], C. albicans infection [OR = 1.7 (1.06-2.82); P = 0.027] and echinocandin as primary agent [OR = 0.6 (0.36-0.99); P = 0.047] were significantly associated with mortality. Candidaemia is a deadly infection. Fluconazole resistance is emerging, although it was not significantly related to mortality. Using an echinocandin as the primary agent could be life-saving.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidemia; Drug Resistance, Multiple, Fungal; Echinocandins; Female; Fluconazole; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Turkey; Voriconazole

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

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

Topics: Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidemia; Candidiasis, Cutaneous; Coinfection; Drug Resistance, Multiple, Fungal; Fluconazole; Hospitalization; Humans; Male; Microbial Sensitivity Tests; Saccharomycetales; Vietnam

We evaluated the epidemiology, clinical characteristics, microbiology, outcomes, and risk factors for mortality of candidemia in adult surgical patients in Shenyang from 2012 to 2018.. We designed a retrospective observational study of adult patients with candidemia in a teaching hospital including three hospital campuses. Data regarding clinical and demographic characteristics were collected from the patient's medical records.. Of the 236 cases of candidemia, 172 (72.9%) were identified in surgical patients, including 146 (84.9%) general surgeries, 11 (6.4%) urologic surgeries, 6 (3.5%) thoracic surgeries, and others. Higher proportions of solid tumors, total parenteral nutrition, the presence of a urinary catheter, and the presence of a gastric tube were observed in surgical patients with candidemia versus non-surgical ones, whereas the percentages of hematological malignancy, diabetes mellitus, and renal replacement therapy were relatively lower in surgical patients. Renal failure, leukopenia, and thrombocytopenia were less common laboratory findings in surgical patients with candidemia than compared to non-surgical ones. Among surgical patients with candidemia, Candida parapsilosis was the predominant species (43%), followed by C. albicans (33.7%), C. glabrata (11%), C. tropicalis (8.1%), and others (4.1%). Overall susceptibility, susceptible dose dependent or intermediate susceptibility, and resistance to fluconazole were detected in 73.3, 19.8, and 3.5% Candida isolates from surgical patients, respectively, but no resistance to amphotericin B was observed. Overall, the 30-day mortality in surgical patients was 19.2%. At multivariable analysis, independent risk factors for death in surgical patients with candidemia were ICU stay, thrombocytopenia, and C. albicans infection.. Surgical patients account for the majority of candidemia cases. Among patients with recent surgery, risk factors for species distribution, antifungal sensitivity patterns of Candida isolates causing candidemia, and independent risk factors for mortality should be evaluated and considered for a better outcome in the antifungal treatment.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candida parapsilosis; Candidemia; China; Female; Fluconazole; Hospitals, Teaching; Humans; Incidence; Male; Microbial Sensitivity Tests; Middle Aged; Postoperative Complications; Retrospective Studies; Risk Factors; Treatment Outcome

In this study, a case of candidemia caused by Candida hellenica as the first report in our country was presented. Fluconazole and liposomal amphotericin B treatment was initiated in a 20-year-old male patient in October 2018 due to the diagnosis of candidemia following esophageal surgery. The patient had a history of multiple esophageal operations. The patient was discharged during the last 24 hours due to the lack of fever, improvement in general condition and lack of growth in blood cultures. Germination tube test of the Candida isolate grown in blood culture was negative and the colony morphology in corn meal tween 80 agar was not defining. It was identified as C.hellenica according to the profile obtained from the ID32C® (bioMérieux, France) method based on carbohydrate assimilation. The target ITS regions of the rRNA genes were amplified by polymerase chain reaction and sequenced using suitable primers for the confirmation of the identification on species level. The DNA sequences obtained were searched by using the "National Center for Biotechnology Information (BLAST)" (http://www.ncbi.nlm.nih.gov/ BLAST/) database and the isolate was identified as C.hellenica with a 99% homology with GenBank sequences. MALDI-TOF (Vitek MS, bioMerieux) could not identify the yeast isolate. The reference microdilution method was performed according to the recommendations of the Clinical and Laboratory Standards Institute in order to test the antifungal susceptibility. The minimal inhibitory concentrations for the isolate, determined after 24-hour incubation were 0.25 µg/ml for amphotericin B, 8 µg/ml for fluconazole, 0.25 µg/ml for voriconazole, and 0.25 µg/ml for itraconazole. As our case had a previous history of gastrointestinal tract surgery it was thought that gastrointestinal tract was the endogenous source of candidemia by leading to mucosal disruption and this mucosal disruption might facilitate the translocation of Candida. The carbohydrate assimilation test ID32C®, was able identify the causative agent of candidaemia at the species level in this case. However, uncommon or previously unrecognized organisms may be misidentified by commercial systems. While the phenotypic definition is sufficient in routine laboratories, it is mandatory to confirm the microorganism species definition by DNA sequence analysis, as done in this case. We have presented a correctly identifed and successfully treated candidemia case. Although the candidemia was not mortal in our pat

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidemia; Esophagus; Fluconazole; Humans; Male; Microbial Sensitivity Tests; Postoperative Complications; Young Adult

Candidemia is among the most frequent nosocomial bloodstream infections. Landmark case-control studies on amphotericin B and fluconazole estimated attributable mortality rates of 38% and 49%, respectively. After introduction of echinocandins, these may have decreased.. In a case-control design, 100 consecutive, hospitalised patients with candidemia were enrolled at the University Hospital of Cologne, Germany between 2014 and 2017. Controls were patients without candidemia matched for age, sex, year and duration of hospitalisation, main admission diagnosis and Patient Clinical Complexity Level (PCCL). Main data captured were risk factors for candidemia, attributable mortality rates and diagnostic and therapeutic adherence according to the EQUAL Candida score.. Overall mortality rates for cases and controls were 43% and 17% (P < .001), respectively; day 30 mortality rates were 38% and 11% (P = .03), accounting for an attributable mortality of 26% and 27%. Guideline adherence was higher in surviving vs non-surviving patients: while survivors reached a median of 17 (IQR: 16-19) points, non-surviving cases reached a median 16 (IQR: 14-18) points out of 22 maximum achievable points (P = .028). Risk factors for candidemia were more frequent in cases compared to control patients, especially chronic pulmonary disease (25% vs 16%; P = n.s.), chronic liver disease (21% vs 6%; P = .002), stay on intensive care unit (70% vs 64%; P = n.s.), respiratory failure (56% vs 50%; P = n.s.) and central venous catheter (97% vs 35%; P < .001).. Attributable mortality of nosocomial candidemia is still substantial but has decreased compared to previous studies with similar design.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidemia; Case-Control Studies; Cross Infection; Echinocandins; Female; Germany; Hospital Mortality; Hospitalization; Hospitals, University; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Risk Factors

An epidemiologic surveillance of non-albicans candidemia for a 6-year period was conducted in Korea. Compared to the published epidemiologic data for the previous 6 years, an increase of C. glabrata (from 21.3% to 28.5%) and a decrease of C. parapsilosis (from 36.5% to 24.7%) were noticed. During the study period, C. tropicalis (36.4%) was most frequently isolated non-albicans Candida, followed by C. glabrata (28.5%), C. parapsilosis (24.7%), and C. krusei (2.6%). Replacement of primary amphotericin B treatment with echinocandins (P < 0.001) eliminated amphotericin B resistance (from 7.8% in 2011 to 0% in 2014).

Topics: Amphotericin B; Antifungal Agents; Candida; Candidemia; Drug Resistance, Fungal; Echinocandins; Epidemiological Monitoring; Humans; Republic of Korea

Candida blood steam infection is a life-threatening disease that seems to be under estimated. Understanding epidemiology of such disease is crucial for improved diagnosis, optimized treatment, and better outcome. Through this retrospective study, we aimed to determine the incidence of candidemia in a secondary care hospital, and to describe the epidemiology and outcome of candidemia among adult patients. The incidence of candidemia for all age groups was 0.24, 0.16 and 0.15 cases/1000 patient-days in 2014, 2015 and 2016 respectively. Among adult patients, 82 cases were identified. The patients had the following clinical characteristics with varying proportions: old age, diabetes, antibiotic exposure, use of vascular catheter, abdominal surgery, ICU hospitalization, haemodialysis, and total parenteral nutrition. All-cause 30-day mortality was 54% and ICU hospitalization was a recognized risk factor for death. The leading causative agents were Candida albicans (32%), and Candida parapsilosis (32%), followed by Candida tropicalis (20%), Candida glabrata (13%) and one each by Candida dubliniensis, Candida famata, and Candida auris. Almost all tested isolates were susceptible to caspofungin and amphotericin B. With regard to fluconazole, C. glabrata showed variable susceptibility. Other species were susceptible except one isolate, each of C. parapsilosis and C. auris. The study highlights the growing importance of non-C. albicans Candida species in the etiology of candidemia. Emergence of C. auris is a warning sign and needs to be closely monitored.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidemia; Cross Infection; Drug Resistance, Fungal; Female; Humans; Incidence; Kuwait; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Risk Factors; Secondary Care Centers

Candida albicans is the most frequently isolated fungal species in hospital settings worldwide. However, non-albicans Candida species with decreased susceptibility to antifungals have emerged as an important cause of fungemia. The aims of this study were to determine the species distribution of fungi isolated from the blood samples of patients at a Swedish University Hospital and to define the in vitro susceptibilities of these isolates to nine antifungal agents. In total, 233 yeast isolates from 143 patients were included in this study. Antifungal susceptibility testing was performed using broth dilution Sensititre YeastOne panels, which comprised amphotericin B, 5-flucytosine, fluconazole, itraconazole, voriconazole, posaconazole, anidulafungin, micafungin, and caspofungin. The most common species in all age groups was C. albicans (n = 93, 65%), followed by C. glabrata (n = 27, 19%) and C. parapsilosis (n = 15, 10%). C. glabrata was mostly found in elderly individuals, while C. parapsilosis was found mainly in young children (p = 0.008). Antifungal resistance was low in the Candida species, except for reduced susceptibility to fluconazole among C. glabrata strains. C. albicans is the most frequent colonizer of Swedish patients. In general antifungal resistance is uncommon in Candida species. Nevertheless, reduced susceptibilities to fluconazole and echinocandins were found in C. glabrata and C. parapsilosis, respectively.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Anidulafungin; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candidemia; Caspofungin; Child; Child, Preschool; Female; Fluconazole; Flucytosine; Humans; Itraconazole; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Triazoles; Voriconazole; Young Adult

Invasive candidiasis is an important cause of morbidity and mortality, which primarily occurs in intensive care units. The Candida colonization index is an accepted score as an early warning tool for invasive candidiasis. This study was performed in a medical PICU with patients prone to contracting invasive candidiasis, to determine the usefulness of the Candida colonization index in forecasting invasive candidiasis in children. This prospective study including 87 patients (children 1 month to 16 years old with several illnesses and requiring ICU care) was conducted in a 22-bed medical PICU, Health Science University of Kayseri Training and Research Hospital, between January 2015 and September 2016. Those patients not on antifungal therapy, who were expected to stay more than seven days in PICU and had no history of a PICU stay within the previous two months were included in the study. In all patients, rectal, cervical, throat, axillary, perineal and nasal swab cultures, urine culture and blood culture tests were performed at admission and every week throughout their stay. Overall, 2639 swab and urine cultures (mean: 30.3) and 325 blood cultures (mean: 3.73) were obtained from 87 patients and a total of 576 grew Candida spp. In patients' swab and urine cultures C. albicans was detected in 64.5%, C. parapsilosis in 12.1%, C. glabrata in 7.5%, Saccharomyces spp in 3.0 %, C. tropicalis in 2.4%, C. krusei in 2.1% and C. kefyr in 1.2%. Three patients had C. albicans and one had C. parapsilosis growth in blood culture. Sensitivity, specificity, positive predictive value and negative predictive value for CI were found to be 33.73%, 100%, 6.7%, and 100%, respectively. Patients are at risk of fungal infection in paediatric intensive care units. Specificity and the negative predictive value of 100 % indicate that CI is a useful score to rule out the presence of invasive fungal disease. On the other hand, the low rate of sensitivity (33.3 %) and positive predictive value (6,7%) make this score less reliable in forecasting invasive candidiasis in children.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candida; Candidemia; Caspofungin; Child; Child, Preschool; Disease Susceptibility; Feasibility Studies; Female; Fluconazole; Humans; Infant; Intensive Care Units, Pediatric; Itraconazole; Male; Microbial Sensitivity Tests; Organ Specificity; Prospective Studies; Sensitivity and Specificity; Voriconazole

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

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

Bloodstream infection with non-Candida albicans Candida species is one of the serious complications among patients with hematological malignancies who receive long-term prophylactic antifungal agents. Here we describe three cases of Candida fermentati (C. fermentati) candidemia after allogeneic stem cell transplantation for hematological malignancies. Case 1 is fluconazole-breakthrough C. fermentati fungemia, which was well controlled with liposomal amphotericin B. Case 2 and 3 were caspofungin-breakthrough C. fermentati fungemia. In case 2, blood culture turned negative for Candida responding to liposomal amphotericin B. Although in vitro susceptibility data for the isolated pathogen suggested the efficacy of both caspofungin and liposomal amphotericin B in all three cases, clinically liposomal amphotericin B seemed to have been more effective for eradication of the pathogen from blood stream. C. fermentati needs to be considered as a possible cause for breakthrough candidemia among post-transplant patients with prolonged antifungal prophylaxis. Discrepancy between in vitro and in vivo susceptibility to antifungals, especially to echinocandins, might provide a clue for the optimal choice of antifungals for C. fermentati infections.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidemia; Caspofungin; DNA, Ribosomal; Echinocandins; Fatal Outcome; Female; Fluconazole; Hematopoietic Stem Cell Transplantation; Humans; Lipopeptides; Lymphoproliferative Disorders; Male; Middle Aged; Sequence Analysis, DNA

Amphotericin B (AmB) is one of the most used drugs for the treatment of systemic fungal infections; however, the treatment causes several toxic manifestations, including nephrotoxicity and hemolytic anemia. Chitosan-coated poly(lactide-co-glycolide) (PLGA) nanoparticles containing AmB were developed with the aim to decrease AmB toxicity and propose the oral route for AmB delivery. In this work, the antifungal efficacy of chitosan-coated PLGA nanoparticles containing AmB was evaluated in 20 strains of fungus isolates from patients with vulvovaginal candidiasis (01 Candida glabrata and 03 Candida albicans), bloodstream infections (04 C. albicans and 01 C. tropicalis) and patients with urinary tract infection (04 Candida albicans, 02 Trichosporon asahii, 01 C. guilhermondii, 03 C. glabrata) and 01 Candida albicans ATCC 90028. Moreover, the cytotoxicity over erythrocytes was evaluated. The single-emulsion solvent evaporation method was suitable for obtaining chitosan-coated PGLA nanoparticles containing AmB. Nanoparticles were spherical in shape, presented mean particle size about 460 nm, positive zeta potential and encapsulation efficiency of 42%. Moreover, nanoparticles prolonged the AmB release. All the strains were susceptible to plain AmB and nanostructured AmB, according to EUCAST breakpoint version 8.1 (resistant > 1 μg/mL), using broth microdilution method. In C. albicans (urine, blood, and vulvovaginal secretion isolates, and 1 ATCC), the MIC value of AmB-loaded nanoparticles varied from 0.25 to 0.5 μg/mL and EUCAST varied from 0.03 to 0.5 μg/mL. In urine and vulvovaginal secretion isolates of C. glabrata, the MIC value of AmB-loaded nanoparticles varied from 0.25 to 0.5 μg/mL and EUCAST varied from 0.03 to 0.015 μg/mL. In urine isolates of C. guilhermondii, the MIC value of AmB-loaded nanoparticles was 0.12 μg/mL and EUCAST was 0.06 μg/mL. In blood isolates of C. tropicalis, the MIC value of AmB-loaded nanoparticles was 0.5 μg/mL and EUCAST was 0.25 μg/mL. Finally, in urine isolates of T asahii, the MIC value of AmB-loaded nanoparticles was 1 μg/mL and EUCAST varied from 0.5 to 1 μg/mL. In the cytotoxicity assay, plain AmB was highly hemolytic (100% in 24 h) while AmB-loaded chitosan/PLGA nanoparticles presented negligible hemolysis.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candidemia; Candidiasis, Vulvovaginal; Chitosan; Drug Carriers; Female; Humans; Lactic Acid; Microbial Sensitivity Tests; Nanoparticles; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Trichosporon; Urinary Tract Infections

The emerging human fungal pathogen Candida auris has been recognized as a multidrug resistant species and is associated with high mortality. This fungus was first described in Japan in 2009 and has been reported in at least 18 countries on five continents. In this study, we report the first isolate of C. auris from the bronchoalveolar lavage fluid (BALF) of a hospitalized woman in China. Interestingly, this isolate is susceptible to all tested antifungals including amphotericin B, fluconazole, and caspofungin. Copper sulfate (CuSO

Topics: Aged; Amphotericin B; Animals; Antifungal Agents; Bronchoalveolar Lavage Fluid; Candida; Candidemia; Caspofungin; China; Copper Sulfate; Echinocandins; Female; Fluconazole; Humans; Lipopeptides; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Moths

Micafungin was reported to be non-inferior to liposomal amphotericin B (LAmB) in treating patients with candidaemia and invasive candidiasis (IC). The current study aimed to evaluate the economic impact of using micafungin versus LAmB for treatment of candidaemia and IC in Turkey. A decision analytic model, which depicted economic consequences upon administration of micafungin or LAmB for treating patients with candidaemia and IC in the Turkish hospitals, was constructed. Patients were switched to an alternative antifungal agent if initial treatment failed due to mycological persistence. All patients were followed up until treatment success or death. Outcome probabilities were obtained from published literature and cost inputs were derived from the latest Turkish resources. Expert panels were used to estimate data that were not available in the literature. Cost per patient treated for each intervention was then calculated. Sensitivity analyses including Monte Carlo simulation were performed. For treatment of candidaemia and IC, micafungin (€4809) was associated with higher total cost than LAmB (€4467), with an additional cost of €341 per treated patient. Cost of initial antifungal treatment was the major cost driver for both comparators. The model outcome was robust over a wide variation in input variables except for drug acquisition cost and duration of initial antifungal treatment with micafungin or LAmB. LAmB is cost-saving relative to micafungin for the treatment of candidaemia and IC from the Turkish hospital perspective, with variation in drug acquisition cost of the critical factor affecting the model outcome.

Topics: Amphotericin B; Antifungal Agents; Candidemia; Candidiasis, Invasive; Cost-Benefit Analysis; Decision Support Techniques; Humans; Micafungin; Treatment Outcome; Turkey

We determined micafungin, caspofungin and amphotericin B (AMB) minimum inhibitory concentration (MICs) and killing rates in RPMI-1640 and in RPMI-1640 with 50% serum against three Candida krusei bloodstream isolates. MIC ranges in RPMI-1640 were 0.125-0.25, 0.25 and 0.125-0.5 mg/L, in RPMI-1640 with 50% serum, MICs were 64-128-, 8- and 4-16-fold higher, respectively. In RPMI-1640 micafungin and caspofungin at 1, 4, 16 and 32 mg/L as well as AMB at 2 mg/L were fungicidal against all isolates in ≤3.96, ≤4.42 and 14.96 h, respectively. In RPMI-1640 with 50% serum, caspofungin was fungicidal for all isolates only at 32 mg/L, micafungin and AMB were fungistatic. In neutropenic mice, 5 mg/kg caspofungin and 1 mg/kg AMB were ineffective against two of the three isolates. Thus, in vivo efficacy of echinocandins and AMB is weak or absent against C. krusei. Prescribers treating C. krusei infections with echinocandins should watch out for clinical resistance and therapeutic failure.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida; Candidemia; Caspofungin; Disease Models, Animal; Drug Evaluation, Preclinical; Humans; Micafungin; Microbial Sensitivity Tests

Topics: Amphotericin B; Antifungal Agents; Aortic Valve; Burns; Candida tropicalis; Candidemia; Echocardiography; Endocarditis; Heart Valve Prosthesis Implantation; Hospitalization; Humans; Invasive Fungal Infections; Male; Micafungin; Middle Aged; Mitral Valve

To identify the risk factors associated with Candida auris candidaemia, as this fungus now poses a global threat.. We performed a subgroup analysis of a previously reported study of 27 Indian ICUs. The clinical data of candidaemia cases due to C. auris and other Candida species were compared to determine significant risk factors associated with C. auris infection.. Of the 1400 candidaemia cases reported earlier, 74 (5.3%) from 19 of 27 ICUs were due to C. auris . The duration of ICU stay prior to candidaemia diagnosis was significantly longer in patients with C. auris candidaemia (median 25, IQR 12-45 days) compared with the non- auris group (median 15, IQR 9-28, P  <   0.001). Based on logistic regression modelling, admission to north Indian ICUs [OR 2.1 (1.2-3.8); P  =   0.012], public-sector hospital [OR 2.2 (1.2-3.9); P  =   0.006], underlying respiratory illness [OR 2.1 (1.3-3.6); P  =   0.002], vascular surgery [OR 2.3 (1.00-5.36); P  =   0.048], prior antifungal exposure [OR 2.8 (1.6-4.8); P  <   0.001] and low APACHE II score [OR 0.8 (0.8-0.9); P  =   0.007] were significantly associated with C. auris candidaemia. The majority (45/51, 88.2%) of the isolates were clonal. A considerable number of isolates were resistant to fluconazole ( n  =   43, 58.1%), amphotericin B ( n  =   10, 13.5%) and caspofungin ( n  =   7, 9.5%).. Although C. auris infection has been observed across India, the number of cases is higher in public-sector hospitals in the north of the country. Longer stay in ICU, underlying respiratory illness, vascular surgery, medical intervention and antifungal exposure are the major risk factors for acquiring C. auris infection even among patients showing lower levels of morbidity.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidemia; Caspofungin; Echinocandins; Female; Fluconazole; Humans; India; Intensive Care Units; Lipopeptides; Male; Microbial Sensitivity Tests; Middle Aged; Mycological Typing Techniques; Risk Factors; Young Adult

The incidence of candidemia is increasing in developing countries. Very little is known about the epidemiology of candidemia in Peru. The aim of this study is to describe the incidence, microbiology, clinical presentation and outcomes of Candida bloodstream infections in three Lima-Callao hospitals.. Candida spp. isolates were identified prospectively at participant hospitals between November 2013 and January 2015. Susceptibility testing for amphotericin B, fluconazole, posaconazole, voriconazole and anidulafungin was performed using broth microdilution method. Clinical information was obtained from medical records and evaluated.. We collected information on 158 isolates and 157 patients. Median age of patients was 55.0 yrs., and 64.1% were males. Thirty-eight (24.2%) episodes of candidemia occurred in those <18 yrs. The frequency of non-Candida albicans was 72.1%. The most frequently recovered species were C. albicans (n = 44, 27.8%), C. parapsilosis (n = 40, 25.3%), C. tropicalis (n = 39, 24.7%) and C. glabrata (n = 15, 9.5%). Only four isolates were resistant to fluconazole, 86.7% (n = 137) were susceptible and 17 were susceptible-dose dependent. Decreased susceptibility to posaconazole was also observed in three isolates, and one to voriconazole. All isolates were susceptible to anidulafungin and amphotericin B. The most commonly associated co-morbid conditions were recent surgery (n = 61, 38.9%), mechanical ventilation (n = 60, 38.2%) and total parenteral nutrition (n = 57, 36.3%). The incidence of candidemia by center ranged between 1.01 and 2.63 cases per 1,000 admissions, with a global incidence of 2.04. Only 28.1% of cases received treatment within 72 hrs. of diagnosis. Overall, the 30-day survival was 60.4% (treated subjects, 67.4%; not-treated patients, 50.9%).. We found a very high proportion of non-albicans Candida species. Despite this, the decreased susceptibility/resistance to fluconazole was only 13.3% and not seen in the other antifungals. Overall, the incidence of candidemia mortality was high when compared to other international studies. It is possible, that the delay in initiating antifungal treatment contributed to the elevated mortality rate, in spite of low antifungal resistance.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anidulafungin; Antifungal Agents; Candida; Candidemia; Child; Child, Preschool; Drug Resistance, Fungal; Echinocandins; Female; Fluconazole; Humans; Incidence; Infant; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Peru; Prospective Studies; Triazoles; Voriconazole; Young Adult

A total of 59

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida parapsilosis; Candidemia; Echinocandins; Humans; Polymerase Chain Reaction; Prohibitins

The 28-day crude mortality rate in 68 cancer patients with fluconazole-susceptible dose-dependent

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida glabrata; Candidemia; Drug Resistance, Fungal; Echinocandins; Female; Fluconazole; Humans; Male; Middle Aged; Neoplasms; Polyenes; Retrospective Studies

To investigate the species distribution and antifungal susceptibility profiles of yeast isolates causing invasive infections across Beijing.. A total of 1201 yeast isolates recovered from blood and other sterile body fluids were correctly identified by matrix-assisted laser desorption/ionization TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute broth microdilution method.. Candida (95.5%) remained the most common yeast species isolated; Candida albicans (38.8%) and Candida parapsilosis (22.6%) were the leading species of candidemia. Azole resistances were mainly observed in Candida glabrata and Candida tropicalis isolates.. This study outlined the epidemiologic data of invasive yeast infections and highlighted the need for continuous monitoring of azole resistances among C. glabrata and C. tropicalis isolates in Beijing.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Beijing; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidemia; Candidiasis, Invasive; Child; Child, Preschool; Drug Resistance, Fungal; Echinocandins; Epidemiological Monitoring; Female; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Middle Aged; Sequence Analysis, DNA; Triazoles; Yeasts; Young Adult

Candida spp. vertebral osteomyelitis is rare. Clinical presentation is unspecific. Diagnosis requires mycological culture of a biopsy specimen. Therapeutic management is based on prolonged course of azole or liposomal amphotericin B. We report the case of Candida tropicalis vertebral osteomyelitis with epidural involvement in a 27 years-old male patient, followed for S-β-thalassemia and with a history of candidemia. The fungus was isolated from a needle biopsy of the vertebral disk. The outcome was favorable under antifungal treatment by amphotericin B and voriconazole.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida tropicalis; Candidemia; Humans; Male; Osteomyelitis; Voriconazole

Small bowel transplantation (SBT) can be a life-saving medical procedure. However, these recipients experience high risk of bloodstream infections caused by Candida. This research aims to characterise the SBT recipient gut microbiota over time following transplantation and investigate the epidemiology of candidaemia in seven paediatric patients. Candida species from the recipients' ileum and bloodstream were identified by internal transcribed spacer sequence and distinguished to strain by multilocus sequence typing and randomly amplified polymorphic DNA. Antifungal susceptibility of bloodstream isolates was determined against nine antifungals. Twenty-two ileostomy samples harboured at least one Candida species. Fungaemia were caused by Candida parapsilosis, Candida albicans, Candida glabrata, Candida orthopsilosis and Candida pelliculosa. All but three bloodstream isolates showed susceptibility to all the antifungals tested. One C. glabrata isolate showed multidrug resistance to itraconazole, amphotericin B and posaconazole and intermediate resistance to caspofungin. Results are congruent with both endogenous (C. albicans, C. glabrata) and exogenous (C. parapsilosis) infections; results also suggest two patients were infected by the same strain of C. parapsilosis. Continuing to work towards a better understanding of sources of infection-particularly the exogenous sources-would lead to targeted prevention strategies.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Candida; Candidemia; Caspofungin; DNA, Fungal; Drug Resistance, Fungal; Echinocandins; Female; Humans; Intestine, Small; Itraconazole; Lipopeptides; Male; Multilocus Sequence Typing; Sequence Analysis, DNA; Transplant Recipients; Triazoles; Young Adult

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

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

The incidence of Candida bloodstream infections (BSIs) has increased over time, especially in medical wards. The objective of this study was to evaluate the impact of different antifungal treatment strategies on 30-day mortality in patients with Candida BSI not admitted to intensive care units (ICUs) at disease onset. This prospective, monocentric, cohort study was conducted at an 1100-bed university hospital in Rome, Italy, where an infectious disease consultation team was implemented. All cases of Candida BSIs observed in adult patients from November 2012 to April 2014 were included. Patients were grouped according to the initial antifungal strategy: fluconazole, echinocandin, or liposomal amphotericin B. Cox regression analysis was used to identify risk factors significantly associated with 15-day and 30-day mortality. During the study period, 130 patients with candidemia were observed (58 % with C. albicans, 7 % with C. glabrata, and 23 % with C. parapsilosis). The first antifungal drug was fluconazole for 40 % of patients, echinocandin for 57.0 %, and liposomal amphotericin B for 4 %. During follow-up, 33 % of patients died. The cumulative mortality 30 days after the candidemia episode was 30.8 % and was similar among groups. In the Cox regression analysis, clinical presentation was the only independent factor associated with 15-day mortality, and Acute Physiology and Chronic Health Evaluation (APACHE) II score and clinical presentation were the independent factors associated with 30-day mortality. No differences in 15-day and 30-day mortality were observed between patients with and without C. albicans candidemia. In patients with candidemia admitted to medical or surgical wards, clinical severity but not the initial antifungal strategy were significantly correlated with mortality.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candida glabrata; Candidemia; Cohort Studies; Echinocandins; Female; Fluconazole; Fungal Proteins; Hospitalization; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Severity of Illness Index; Systemic Inflammatory Response Syndrome

Adult data suggest that echinocandins for treatment of candidaemia are associated with decreased mortality, attributed to their fungicidal activity. There are limited data comparing antifungals in children. We compared 30-day all-cause mortality among paediatric candidaemia patients treated with fungicidal vs. fungistatic agents. All inpatients (>6 months and <19 years of age) with candidaemia between 2000 and 2012 at The Children's Hospital of Philadelphia were retrospectively identified. Definitive therapy with fungicidal (amphotericin B and caspofungin) agents was compared with fungistatic (fluconazole) agents. A propensity score model generated the inverse probability of receiving a fungicidal agent, which was included in a weighted logistic regression model. Among 203 children meeting inclusion criteria, 151 (74.4%) and 52 (25.6%) received a fungicidal and fungistatic agent, respectively. Overall, 18 (8.9%) patients died within 30 days. There was no statistically significant difference in mortality between patients started on a fungicidal or fungistatic agent (OR: 2.19, 95% CI: 0.42-11.48). In a propensity score-weighted model, definitive therapy with a fungicidal agent did not result in a significant decrease in mortality. These data suggest that both agents can be considered definitive therapy for paediatric candidaemia. The results should be interpreted with caution given the small sample size. Larger cohort studies are needed.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candidemia; Caspofungin; Child; Child, Preschool; Cohort Studies; Echinocandins; Fluconazole; Humans; Infant; Inpatients; Lipopeptides; Retrospective Studies; Treatment Outcome

Candida glabrata isolates have reduced in vitro susceptibility to azoles, which raises concerns about the clinical effectiveness of fluconazole for treating bloodstream infection (BSI) by this Candida species. We aimed to evaluate whether the choice of initial antifungal treatment (fluconazole versus echinocandins or liposomal amphotericin B [L-AmB]-based regimens) has an impact on the outcome of C. glabrata BSI. We analyzed data from a prospective, multicenter, population-based surveillance program on candidemia conducted in 5 metropolitan areas of Spain (May 2010 to April 2011). Adult patients with an episode of C. glabrata BSI were included. The main outcomes were 14-day mortality and treatment failure (14-day mortality and/or persistent C. glabrata BSI for ≥48 h despite antifungal initiation). The impact of using fluconazole as initial antifungal treatment on the patients' prognosis was assessed by logistic regression analysis with the addition of a propensity score approach. A total of 94 patients with C. glabrata BSI were identified. Of these, 34 had received fluconazole and 35 had received an echinocandin/L-AmB-based regimen. Patients in the echinocandin/L-AmB group had poorer baseline clinical status than did those in the fluconazole group. Patients in the fluconazole group were more frequently (55.9% versus 28.6%) and much earlier (median time, 3 versus 7 days) switched to another antifungal regimen. Overall, 14-day mortality was 13% (9/69) and treatment failure 34.8% (24/69), with no significant differences between the groups. On multivariate analysis, after adjusting for baseline characteristics by propensity score, fluconazole use was not associated with an unfavorable evolution (adjusted odds ratio [OR] for 14-day mortality, 1.16, with 95% confidence interval [CI] of 0.22 to 6.17; adjusted OR for treatment failure, 0.83, with 95% CI of 0.27 to 2.61). In conclusion, initial fluconazole treatment was not associated with a poorer outcome than that obtained with echinocandins/L-AmB regimens in patients with C. glabrata BSI. (This study has been registered at ClinicalTrials.gov under registration no. NCT01236261.).

Topics: Aged; Amphotericin B; Antifungal Agents; Candida glabrata; Candidemia; Echinocandins; Female; Fluconazole; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies

Candida tropicalis is the fourth most common cause of candidaemia in hospitalized patients and associated mortality is high. C. tropicalis frequently causes biofilm-related infections. Echinocandins and amphotericin B show potent in vitro activity against C. albicans biofilms, but their activity against C. tropicalis biofilms has received little attention.. We studied production of biofilm by 54 C. tropicalis isolates from blood and the antifungal susceptibility of these isolates to micafungin, amphotericin B and liposomal amphotericin B. Biofilm production was measured using the crystal violet assay to determine biomass and the XTT reduction assay to determine metabolic activity. The antifungal susceptibility of planktonic and sessile cells was measured using the EUCAST EDef 7.2 procedure and XTT reduction assay, respectively. The sessile MIC endpoint of SMIC80 was defined as an 80% reduction in the metabolic activity of the biofilm treated with the antifungal compared with the control well.. The three drugs were very active against the isolates in planktonic form, with micafungin showing the highest activity (P < 0.001). Micafungin was the most active agent against C. tropicalis biofilms (P < 0.001). In contrast, liposomal amphotericin B showed poor antifungal activity.. Micafungin was the most active drug against C. tropicalis biofilm. Although the echinocandins and liposomal amphotericin B are considered very active against Candida spp. biofilms, this is not true for C. tropicalis, as liposomal amphotericin B showed poor antifungal activity against biofilms.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Biomass; Candida tropicalis; Candidemia; Echinocandins; Formazans; Gentian Violet; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Staining and Labeling; Tetrazolium Salts

Characterization of a hospital outbreak of Candida auris candidemia that involved 18 critically ill patients in Venezuela.. Bloodstream isolates of C. auris obtained from 18 patients admitted at a medical center in Maracaibo, between March, 2012 and July, 2013 were included. Species identification was confirmed by ITS rDNA sequencing. Isolates were subsequently typed by amplified fragment length polymorphism fingerprinting (AFLP). Susceptibility testing was performed according to CLSI. Clinical data were collected from all cases by using a standard clinical form.. A total of 13 critically ill pediatric and 5 adult patients, with a median age of 26 days, were included. All were previously exposed to antibiotics and multiple invasive medical procedures. Clinical management included prompt catheter removal and antifungal therapy. Thirteen patients (72%) survived up to 30 days after onset of candidemia. AFLP fingerprinting of all C. auris isolates suggested a clonal outbreak. The isolates were considered resistant to azoles, but susceptible to anidulafungin and 50% of isolates exhibited amphotericin B MIC values of >1 μg/ml.. The study demonstrated that C. auris is a multiresistant yeast pathogen that can be a source of health-care associated infections in tertiary care hospitals with a high potential for nosocomial horizontal transmission.

Topics: Adult; Aged; Americas; Amphotericin B; Amplified Fragment Length Polymorphism Analysis; Anidulafungin; Antifungal Agents; Azoles; Candida; Candidemia; Cross Infection; Disease Outbreaks; DNA, Fungal; Drug Resistance, Fungal; Echinocandins; Female; Humans; Infant, Newborn; Male; Microbial Sensitivity Tests; Venezuela; Young Adult

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida glabrata; Candidemia; Echinocandins; Humans; Male; Microbial Sensitivity Tests; Molecular Sequence Data; Neutropenia; Sequence Analysis, DNA

A case of persistent candidemia in a preterm neonate caused by Candida fermentati, identified by sequencing of the internally transcribed spacer region of ribosomal DNA (rDNA), is described. The neonate was treated for 30 days by combination therapy with amphotericin B (AmBisome) and caspofungin with a successful outcome, and no drug-related side effects were observed.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidemia; Caspofungin; DNA, Fungal; DNA, Intergenic; Drug Therapy, Combination; Echinocandins; Humans; Infant, Newborn; Infant, Premature; Lipopeptides; Male; Molecular Sequence Data; Sequence Analysis, DNA; Treatment Outcome

Candida species has become the seventh most frequent causal microorganisms of nosocomial sepsis. Prematurity and low birth weights are strongly associated with the development of neonatal nosocomial bloodstream infections. Candida albicans has been the species most often associated with neonatal infections, but recently, there has been a changing pattern in the isolates recovered from neonates with invasive candidiasis, which poses resistance to the existing class of azoles such as fluconazole antifungals along with cross resistance to newer triazoles, which results in a therapeutic challenge in invasive fungal infections causing high incidence of mortality. Candida species was isolated from blood of neonates and children younger than 15 years admitted to hospital and susceptible for Candida-induced sepsis. Polymerase chain reaction-based identification and confirmation of individual Candida species were done using DNA sequencing. Antibiotic susceptibility assay and resistance pattern for fluconazole, voriconazole, and amphotericin were done for all the isolates. Furthermore, the change in free radical, cytokine release, and nitric oxide synthase expression and nitric oxide release from polymorphonuclear leukocytes isolated from control and pediatric sepsis cases were also performed. The present study probably for the first time reports the change in increasing incidence of nonalbicans Candida-induced sepsis in neonates and children admitted to the intensive care unit of hospital, and current antibiotics load posing resistance for antifungal treatment strategy and provide serious threats in future treatment. The increase in free radicals in polymorphonuclear leukocytes and increase in expression of nitric oxide synthase expression and nitric oxide release in Candida-infected pediatric sepsis cases underlie the role of host factor in dissemination and invasiveness of infection from exogenous sources and pathogenesis of systemic inflammation during sepsis.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candida; Candidemia; Candidiasis; Child; Child, Preschool; Cross Infection; Cytokines; Female; Fluconazole; Free Radicals; Humans; Incidence; India; Infant; Infant, Newborn; Intensive Care Units; Interleukin-10; Interleukin-1beta; Male; Microbial Sensitivity Tests; Nitric Oxide; Nitric Oxide Synthase; Sepsis; Tumor Necrosis Factor-alpha; Voriconazole

Amphotericin B (Ampho B) isa fungicidal drug that causes cell wall injury. Pharmacological ascorbate induces the extracellular prooxidants, which might enter the Ampho B-induced cell wall porosity and act synergistically.W e tested low-dose Ampho B with a short course of pharmacological ascorbate using a mouse model of sepsis preconditioned with an injection of Candida albicans 6 h prior to cecal ligation and puncture (CLP). In this model, candidemia reappeared as early as 6 h after CLP with a predictably high mortality rate. This characteristic mimics sepsis in the phase of immunosuppression inpatients. Using the model, at 12- and 18-h post-CLP, we administered isotonic (pH neutralized) pharmacological ascorbate intravenously with low-dose Ampho B or sodium deoxycholate, vehicle-controlled, administered IP. The survival rate of low-dose Ampho B plus ascorbate was 53%, compared with < 11% for low-dose Ampho B or high-dose Ampho B alone. In addition, a beneficial effect was demonstrated in terms of kidney damage,liver injury, spleen histopathology, and serum markers at 24 h after CLP. Kidney injury was less severe in low-dose Ampho B plus ascorbate combination therapy due to less severe sepsis. Moreover, ascorbate enhanced the effectiveness of phagocytosis against C. albicans in human phagocytic cells. Taken together, the data indicate that the new mouse model simulates sepsis-induced immunosuppression and that the combination of pharmacological ascorbate with an antifungal drug is a potentially effective treatment that may reduce nephrotoxicity, and perhaps also increase fungicidal activity in patients with systemic candidiasis caused by Candida albicans.

Topics: Amphotericin B; Animals; Ascorbic Acid; Candidemia; Disease Models, Animal; Drug Combinations; Kidney; Liver; Male; Mice, Inbred BALB C; Sepsis; Spleen

We undertook the present study to ascertain the contributing risk factors and explore the epidemiological and mycological characteristics of opportunistic candidemia among patients with hematological malignancies.. Observational cross-sectional study in a tertiary care center.. Consecutive patients with hematological malignancies reporting to the collaborating medical and pediatric units with a febrile episode were recruited and screened for candidemia by blood culture. Recovered Candida isolates were speciated and antifungal susceptibility testing was performed as per Clinical and Laboratory Standards Institute guideline (CLSI) guidelines M44-A. Further analysis was done for potential risk factors and compared between culture positive and negative patients.. Of 150 patients recruited, the majority (n=27) were between 51 and 60 years and the male to female ratio was 1.63:1. Fifteen patients (10%) were culture positive. The culture positivity was significantly higher in acute lymphocytic leukemia (ALL) than in non-ALL patients (p=0.03). There was significant association of candidaemia with leucopenia, chemotherapeutic drugs, corticosteroids and presence of indwelling devices. Duration of disease (p=0.032) and duration of hospitalization (p=0.003) were significantly prolonged in culture positive patients. C. tropicalis was the commonest isolate (46.67%), with non- Candida albicans outnumbering C. albicans in all categories of hematological malignancies (2.75:1). All isolates of C. albicans were uniformly sensitive to all the azoles, but only 50% were sensitive to amphotericin B and none to nystatin and flucytosine.. This observational study identifies ALL and chronic lymphocytic leukemia (CLL) as the forms of hematological malignancy predominantly associated with candidemia; specifies risk factors and chemotherapeutic agents predisposing patients towards its occurrence; reports a preponderance of C. tropicalis among the causative agents and finds voriconazole to be the most effective antifungal agent against the recovered isolates. This information could assist in tailoring prophylactic and therapeutic antifungal practices for this infection, according to local epidemiological and mycological characteristics.

Topics: Amphotericin B; Candida albicans; Candida tropicalis; Candidemia; Cross-Sectional Studies; Female; Hematologic Neoplasms; Humans; India; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Nystatin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prevalence; Risk Factors; Tertiary Care Centers; Voriconazole

Bloodstream infections (BSI) caused by various Candida spp. are a significant cause of morbidity and mortality in hospitalized patients. An increasing proportion of device- related infections, particularly those involving the bloodstream and urinary tract, are being caused by Candida spp.. This study was conducted to evaluate the different species of Candida causing blood stream infections and their antifungal susceptibility.. The present study was conducted on 12464 blood samples received for culture, the samples were incubated at 37ºC for overnight and inoculated on culture plate next day. The growth on culture plates was identified by standard microbiological techniques and their antifungal susceptibility was put up as per Centre for Laboratory Standard Institute guidelines.. Out of 12464 blood samples, isolation rate of Candida spp was 7.25%, which was higher in paediatric age group patients (89%) as compared to adults (11%). BSIs due to Candida spp. was significantly more common among ICUs (72%) than non-ICU settings (28%). C. tropicalis was the commonest (43%) species isolated followed by C. albicans (41%), C. krusei (9%) and C. parapsilosis (7%). All strains were 100% sensitive to Amphotericin B.. There is a changing trend of increased isolation of non albicans Candida spp. than Candida albicans. It was common in ICUs settings and in paediatric age group. All isolates were found 100% sensitive to Amphotericin-B, C.krusei was 100% resistant to fluconazole followed by C. tropicalis 32.6% and C. parapsilosis 28.58%.

Topics: Adolescent; Adult; Age Factors; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candidemia; Child; Child, Preschool; Drug Resistance, Fungal; Female; Fluconazole; Humans; Infant; Intensive Care Units; Male; Microbial Sensitivity Tests; Risk Factors; Tertiary Care Centers; Young Adult

The incidence of invasive candidiasis caused by non-albicans Candida (NAC) spp. is increasing. The aim of this analysis was to evaluate the efficacy of micafungin, caspofungin and liposomal amphotericin B in patients with invasive candidiasis and candidaemia caused by different Candida spp. This post hoc analysis used data obtained from two randomised phase III trials was conducted to evaluate the efficacy and safety of micafungin vs. caspofungin and micafungin vs. liposomal amphotericin B. Treatment success, clinical response, mycological response and mortality were evaluated in patients infected with C. albicans and NAC spp. Treatment success rates in patients with either C. albicans or NAC infections were similar. Outcomes were similar for micafungin, caspofungin and liposomal amphotericin B. Candida albicans was the most prevalent pathogen recovered (41.0%), followed by C. tropicalis (17.9%), C. parapsilosis (14.4%), C. glabrata (10.4%), multiple Candida spp. (7.3%) and C. krusei (3.2%). Age, primary diagnosis (i.e. candidaemia or invasive candidiasis), previous corticosteroid therapy and Acute Physiology and Chronic Health Evaluation II score were identified as potential predictors of treatment success and mortality. Micafungin, caspofungin and liposomal amphotericin B exhibit favourable treatment response rates that are comparable for patients infected with different Candida spp.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidemia; Candidiasis, Invasive; Caspofungin; Clinical Trials, Phase III as Topic; Echinocandins; Female; Humans; Lipopeptides; Male; Micafungin; Middle Aged; Survival Analysis; Treatment Outcome; Young Adult

We identified a case of breakthrough candidemia in a 25-year-old patient receiving micafungin prophylaxis (50 mg/day). Five Candida glabrata isolates were obtained from blood cultures and were classified as multidrug-resistant isolates, since all of them exhibited high MICs for echinocandin and azole drugs. A mutation (S663F) in hot spot 1 of the FKS2 gene was found in all five isolates. This mutation yielded a 1,3-β-D-glucan synthase enzyme with highly reduced sensitivities to echinocandin drugs.

Topics: Adult; Amphotericin B; Antifungal Agents; Azoles; Candida glabrata; Candidemia; Drug Resistance, Fungal; Echinocandins; Fungal Proteins; Humans; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation

Species distribution and antifungal susceptibility of Candida isolates at one institution were evaluated. Detection rates of fungi were examined for 5 years between 2007 and 2011. Sensitivities of fungi to amphotericin B, flucytosine, fluconazole, micafungin, itraconazole, and voriconazole were evaluated in blood culture-positive patients. A total of 3,832 fungal isolates were detected, including Candida albicans 66.5%, Candida glabrata 20.3%, Candida parapsilosis 6.2%, Candida tropicalis 5.5%, and others 1.5%. Candidemia was diagnosed in 131 patients, and C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and others were present in 42.0%, 27.5%, 16.0%, 8.4%, and 6.1% of these patients, respectively. Voriconazole had the lowest MIC90s against C. albicans and C. parapsilosis (0.015 and 0.25). Micafungin had a low MIC90 against C. glabrata and C. tropicalis. C. albicans was the most common fungus in patients with candidemia. Voriconazole and micafungin were effective against C. albicans. Amphotericin B was effective for C. parapsilosis, and micafungin showed good efficacy against C. glabrata and C. tropicalis.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candida tropicalis; Candidemia; Drug Resistance, Fungal; Echinocandins; Fluconazole; Flucytosine; Health Facilities; Humans; Itraconazole; Japan; Lipopeptides; Micafungin; Time Factors; Voriconazole

Atrioventricular block can occur in normal children, young adults or athletes. It is also associated with underlying heart disease or occurs as a drug adverse effect. Amphotericin B is used in the treatment of invasive fungal infections. Cardiac toxicity is a rare adverse reaction. We report the case of a 9-month girl, admitted in the paediatric intensive care unit with cytomegalovirus pneumonitis. During hospitalisation the patient developed a systemic fungic infection and was medicated with liposomal amphotericin B. On the third day of treatment she began repeated episodes of bradycardia with spontaneous reversion. The investigation revealed a second-degree atrioventricular block. We excluded the misplacement of the central catheter, myocarditis or structural cardiomyopathy and suspended amphotericin. After 8 days, the bradycardia episodes ceased what was consistent with the drug's half-life. Amphotericin cardiotoxic mechanism is still unclear. It may be related with alteration of myocardial membrane depolarisation.

Topics: Amphotericin B; Antifungal Agents; Atrioventricular Block; Candidemia; Cardiotoxicity; Female; Humans; Infant

Candida albicans infections have become increasingly recognised as being biofilm related. Recent studies have shown that there is a relationship between biofilm formation and poor clinical outcomes in patients infected with biofilm proficient strains. Here we have investigated a panel of clinical isolates in an attempt to evaluate their phenotypic and transcriptional properties in an attempt to differentiate and define levels of biofilm formation.. Biofilm formation was shown to be heterogeneous; with isolates being defined as either high or low biofilm formers (LBF and HBF) based on different biomass quantification. These categories could also be differentiated using a cell surface hydrophobicity assay with 24 h biofilms. HBF isolates were more resistance to amphotericin B (AMB) treatment than LBF, but not voriconazole (VRZ). In a Galleria mellonella model of infection HBF mortality was significantly increased in comparison to LBF. Histological analysis of the HBF showed hyphal elements intertwined indicative of the biofilm phenotype. Transcriptional analysis of 23 genes implicated in biofilm formation showed no significant differential expression profiles between LBF and HBF, except for Cdr1 at 4 and 24 h. Cluster analysis showed similar patterns of expression for different functional classes of genes, though correlation analysis of the 4 h biofilms with overall biomass at 24 h showed that 7 genes were correlated with high levels of biofilm, including Als3, Eap1, Cph1, Sap5, Plb1, Cdr1 and Zap1.. Our findings show that biofilm formation is variable amongst C. albicans isolates, and categorising isolates depending on this can be used to predict how pathogenic the isolate will behave clinically. We have shown that looking at individual genes in less informative than looking at multiple genes when trying to categorise isolates at LBF or HBF. These findings are important when developing biofilm-specific diagnostics as these could be used to predict how best to treat patients infected with C. albicans. Further studies are required to evaluate this clinically.

Topics: Amphotericin B; Animals; Antifungal Agents; Biofilms; Biological Assay; Candida albicans; Candidemia; Drug Resistance, Fungal; Gene Expression Profiling; Genetic Variation; Humans; Lepidoptera; Pyrimidines; Survival Analysis; Triazoles; Virulence; Voriconazole

Micafungin was non-inferior to liposomal amphotericin B (LAmB) for the treatment of candidaemia and invasive candidiasis (IC) in a major clinical trial. The present study investigated the economic impact of micafungin vs. LAmB in treating candidaemia and IC. A decision analytical model was constructed to capture downstream consequences of using micafungin or LAmB as primary definitive therapy. The main outcomes were treatment success and treatment failure due to mycological persistence, or death. Outcome probabilities were derived from key published sources. Resource used was estimated by an expert panel and cost inputs were from the latest Australian resources. The analysis was from an Australian hospital perspective. Sensitivity analyses using Monte Carlo simulation were conducted. Micafungin (AU$61 426) had a lower total cost than LAmB (AU$72 382), with a total net cost-saving of AU$10 957 per patient. This was primarily due to the lower cost associated with initial antifungal treatment and shorter length of stay for patients in the micafungin arm. Hospitalisation was the main cost driver for both arms. Results were robust over a wide range of variables. The uncertainty analysis demonstrated that micafungin had a 99.9% chance of being cost-saving compared with LAmB. Micafungin was associated with cost-saving relative to LAmB in the treatment of candidaemia and IC in Australia.

Topics: Amphotericin B; Antifungal Agents; Australia; Candidemia; Candidiasis, Invasive; Echinocandins; Health Care Costs; Humans; Lipopeptides; Micafungin; Treatment Outcome

Invasive fungal infections have increased significantly in the past few decades because of the increase in high-risk populations. To investigate the distribution and drug susceptibilities of such infections, we analyzed all 152 Candida isolates causing candidemia from 2004 to 2006 at the China Medical University Hospital, a medical center in central Taiwan. Candida albicans was the most common species, accounting for 52.6% of the isolates, followed by C. tropicalis (19.7%), C. parapsilosis (14.5%), C. glabrata (8.6%), C. guilliermondii (3.9%), and C. pelliculosa (0.7%). All isolates were susceptible to amphotericin B, anidulafungin, micafungin, and voriconazole according to minimum inhibitory concentrations (MICs) after a 24-h incubation; 0.7%, 6.6%, and 7.9% of isolates were resistant to amphotericin B, fluconazole, and voriconazole, respectively, after 48-h incubation. Both C. albicans and C. parapsilosis had high degrees of agreement for azoles between 24- and 48-h incubation periods, whereas C. glabrata (38.5-46.2%) and C. tropicalis (56.7-63.3%) did not. The majority of the isolates with high azole MICs displayed a trailing growth phenotype. Hence, the MICs of different drugs after 24-h incubation may be considered for prognosis of candidemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Azoles; Candida; Candidemia; Child; Child, Preschool; Drug Resistance, Fungal; Echinocandins; Humans; Infant; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Taiwan; Young Adult

Bloodstream infections due to Candida species are becoming a major cause of morbidity and mortality in hospitalized patients. The spectrum of candidemia has changed with the emergence of non-albicans Candida species, especially among critically ill patients.. In a retrospective study (July 2009 to December 2009) on candidemia, various Candida species isolated from blood cultures were characterized and studied along with the determination of their antifungal susceptibility to amphotericin B, itraconazole, and fluconazole by Etest. Probable risk factors for patients in the intensive care unit (ICU) presenting with candidemia were also analyzed.. During the study period, a total of 4651 samples were received, out of which 468 samples (10.06%) were positive for growth of organisms: 441 (94.20%) aerobic bacterial pathogens and 27 (5.79%) Candida species. The most common Candida spp. isolate was C. tropicalis (40.8%) followed by C. albicans (29.6%), C. glabrata (18.5%) and others (11.1%). Out of the 27 Candida strains, 24 (88.9%) were isolated from patients treated in the ICU. Among these, association of previous use of broad-spectrum antibiotics in 22 patients (91.6%) and central line catheter insertion in 20 patients (83.3%) were found to be statistically significant as compared to non-candidemia patients (p <0.05). Antifungal susceptibility testing of the isolates revealed a lower level of drug resistance to amphotericin B (18.5% of the isolates) versus 77.8% resistance to fluconazole.. Rapid changes in the rate of infection, potential risk factors, and emergence of non-albicans Candida demand continued surveillance of this serious bloodstream fungal infection.

Topics: Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidemia; Drug Resistance, Fungal; Fluconazole; Humans; India; Itraconazole; Microbial Sensitivity Tests; Middle Aged; Prevalence; Retrospective Studies; Risk Factors; Tertiary Care Centers

Candidemia in cancer patients may differ according to the type of cancer. To characterise the epidemiology and outcome of candidemia in cancer patients from Brazilian hospitals, we compared the characteristics of patients with hematologic malignancies (HM) and solid tumours (ST). A retrospective study was performed, based on data collected from laboratory-based surveillance studies in 18 tertiary care hospitals between March/2003 and December/2007. The characteristics of patients with HM (n = 117) were compared with patients with ST (n = 248). Predictors of 30-day mortality were identified by uni- and multivariate analyses. Candidemia in HM was more likely to occur in the setting of chemotherapy, corticosteroids, neutropenia, mucositis and tunnelled central venous catheter (CVC), whereas surgery, intensive care unit admission and invasive procedures (mechanical ventilation, parenteral nutrition and CVC) were more frequent in ST. The 30-day mortality rate was higher in the ST group (65% vs. 46%, P = 0.001). Factors significantly associated with 30-day mortality were older age and intensive care unit admission. Important differences in the epidemiology and outcome of candidemia in HM and ST were observed. The characterisation of the epidemiology is important to drive preventive measures and to select appropriate therapies.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Brazil; Candida; Candidemia; Child; Child, Preschool; Cross Infection; Female; Hematologic Neoplasms; Hospital Mortality; Humans; Infant; Intensive Care Units; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Retrospective Studies; Severity of Illness Index; Survival Analysis; Tertiary Care Centers; Young Adult

Fungemia in preterm infants is associated with high mortality and morbidity. This study reports an outbreak of unusual fungemia in a tertiary neonatal intensive care unit (NICU).. Ten Candida pelliculosa bloodstream isolates were identified from six infants hospitalized in the NICU from February to March 2009. Environmental study was performed, and genetic relatedness among the 10 clinical isolates of C pelliculosa and six control C pelliculosa strains was characterized by randomly amplified polymorphic DNA assay. In vitro susceptibility of isolates to six antifungal agents was analyzed by broth microdilution method. Amphotericin B was given to infected infants and prophylactic fluconazole was prescribed to the other noninfected extremely low birth weight infants during the outbreak.. Thrombocytopenia (platelet counts <100×10(9)/L) was the early laboratory finding in four infants. One of six patients died, making overall mortality 17%. Fluconazole, voriconazole, amphotericin B, and micafungin provided good antifungal activity. Cultures from the environment and hands of caregivers were all negative. Molecular studies indicated the outbreak as caused by a single strain. The outbreak was controlled by strict hand washing, cohort infected patients, confined physicians and nurses to take care of patients, prophylactic fluconazole to uninfected neonates, and proper management of human milk.. The study demonstrated the clinical importance of emerged non-albicans Candida species in NICU. For unusual pathogen isolated from immunocompromised hosts, more attention should be paid to monitor the possibility of an outbreak.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidemia; Disease Outbreaks; Female; Fluconazole; Genotype; Humans; Infant; Infant, Newborn; Infection Control; Intensive Care Units, Neonatal; Male; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Typing; Mycological Typing Techniques; Random Amplified Polymorphic DNA Technique; Treatment Outcome

Candida species are the leading causes of invasive fungal infection among hospitalized patients and are responsible for major economic burdens. The goals of this study were to estimate the costs directly associated with the treatment of candidemia and factors associated with increased costs, as well as the impact of first-line antifungal agents on the outcomes and costs. A retrospective study was conducted in a sample of 199 patients from four university-affiliated tertiary care hospitals in Korea over 1 year. Only costs attributable to the treatment of candidemia were estimated by reviewing resource utilization during treatment. Risk factors for increased costs, treatment outcome, and hospital length of stay (LOS) were analyzed. Approximately 65% of the patients were treated with fluconazole, and 28% were treated with conventional amphotericin B. The overall treatment success rate was 52.8%, and the 30-day mortality rate was 47.9%. Hematologic malignancy, need for mechanical ventilation, and treatment failure of first-line antifungal agents were independent risk factors for mortality. The mean total cost for the treatment of candidemia was $4,743 per patient. Intensive care unit stay at candidemia onset and antifungal switch to second-line agents were independent risk factors for increased costs. The LOS was also significantly longer in patients who switched antifungal agents to second-line drugs. Antifungal switch to second-line agents for any reasons was the only modifiable risk factor of increased costs and LOS. Choosing an appropriate first-line antifungal agent is crucial for better outcomes and reduced hospital costs of candidemia.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candidemia; Deoxycholic Acid; Drug Combinations; Female; Humans; Itraconazole; Male; Middle Aged; Retrospective Studies

Candidemia due to uncommon Candida spp. appears to be increasing in incidence. C. dubliniensis has been increasingly recovered from individuals not infected with HIV. Identification of C. dubliniensis can be problematic in routine clinical practice due to its phenotypic resemblance to C. albicans. We report the first case of C. dubliniensis candidemia in Korea, which occurred in a 64-yr-old woman who presented with partial seizure, drowsiness, and recurrent fever. Germ-tube positive yeast that was isolated from blood and central venous catheter tip cultures formed smooth, white colonies on sheep blood agar and Sabouraud agar plates, indicative of Candida spp. C. dubliniensis was identified using the Vitek 2 system (bioMerieux, USA), latex agglutination, chromogenic agar, and multiplex PCR. The blood isolate was susceptible to flucytosine, fluconazole, voriconazole, and amphotericin B. After removal of the central venous catheter and initiation of fluconazole treatment, the patient's condition gradually improved, and she was cleared for discharge from our hospital. Both clinicians and microbiologists should be aware of predisposing factors to C. dubliniensis candidemia in order to promote early diagnosis and appropriate treatment.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidemia; Catheterization, Central Venous; Female; Fluconazole; Flucytosine; Humans; Microbial Sensitivity Tests; Middle Aged; Pyrimidines; Triazoles; Voriconazole

Amphotericin B (AmB) traditionally has been the mainstay of therapy for children with candidemia but is associated with drug-related toxicities (DRT). Studies investigating the risk factors for AmB DRT in children are limited.. A retrospective review of patients aged 6 months to ≤18 years with candidemia who received ≥1 dose of AmB from 2003 to 2009 was conducted at Texas Children's Hospital, Houston, TX. Patient demographics, risk factors, drug dosages, laboratory adverse effects and infusion-related side effects (INFRT) were recorded.. A total of 223 episodes of candidemia occurred in 179 patients. AmB was administered in 172 (77%) episodes. Amphotericin B deoxycholate, Amphotericin B lipid complex and liposomal Amphotericin B were administered in 65 (38%), 96 (55%) and 11 (6.4%) episodes, respectively. When the first episode of AmB use was analyzed separately (n = 138), DRT occurred in 83% (n = 114); nephrotoxicity occurred in 45% (n = 62), hypokalemia in 47% (n = 62) and INFRT in 31 % (n = 41). The most common INFRT was chills and rigors (80%, n = 33) followed by fever (31.7%, n = 13) and hypotension (9.7%, n = 4). Patients with lower baseline creatinine clearance were at increased risk of having nephrotoxicity than those with higher baseline creatinine clearance (P = 0.004). Nephrotoxicity was less likely in patients who received immunosuppressants (P = 0.02). Neutropenia (P = 0.02) and prior hypokalemia (P = 0.001) were independently associated with hypokalemia. The receipt of premedication was independently associated with a lower likelihood of INFRT (P ≤ 0.0001). It is important to note that most AmB-related DRT was quickly reversible.. AmB-associated DRT was common and reversible in our nonneonatal pediatric population. Prospective studies are required to further evaluate risk factors and determine whether they are modifiable.

Topics: Adolescent; Amphotericin B; Analysis of Variance; Antifungal Agents; Candidemia; Child; Child, Preschool; Female; Humans; Hypokalemia; Infant; Kidney Diseases; Male; Retrospective Studies; Risk Factors

We aim in this study to provide levels of susceptibility of 162 bloodstream isolates of non-Candida albicans and non-C. tropicalis species from a sentinel program conducted in 11 hospitals in Brazil. Additionally, we compared the broth microdilution (BMD) method of the European Committee of Susceptibility Testing (EUCAST) with Clinical Laboratory Standards Institute (CLSI) BMD method for fluconazole, itraconazole, voriconazole, and amphotericin B. The study included 103 C. parapsilosis, 38 C. glabrata, 8 C. orthopsilosis, and 7 C. krusei isolates, and single isolates of Pichia anomala, C. famata, C. lusitaniae, C. kefyr, C. guilliermondii, and C. metapsilosis. Of note, we observed cross-resistance between fluconazole and voriconazole for two isolates being one C. parapsilosis and one C. glabrata. Good essential agreement (EA) was observed between the EUCAST and the CLSI results for C. parapsilosis and for fluconazole, itraconazole, voriconazole, and amphotericin B, respectively: 98%, 99%, 98%, and 97%. Otherwise, for C. glabrata, the EA for fluconazole was 84.2% and for voriconazole 89.4%. Because data from Brazil are scarce, our results contribute to the consolidation of the database of candidemia agents and monitoring of trends in the profile of drug resistance.

Topics: Amphotericin B; Antifungal Agents; Blood; Brazil; Candida; Candidemia; DNA, Fungal; Drug Resistance, Fungal; Fluconazole; Humans; Itraconazole; Microbial Sensitivity Tests; Pichia; Pyrimidines; Tertiary Care Centers; Triazoles; Voriconazole

We investigate the characteristics of the Candida species involved in BSI episodes in our Institute, their phospholipase and protease activity and the susceptibility pattern towards the main antifungal agents currently available. From January 2009 to December 2010 we documented a total of 59 episodes of candidemia. The incidence of candidemia was 32% in General Surgery, 22% in the Intensive Care Unit (ICU), 13% in Oncology and 10% in Gastroenterology. C. albicans was the most common species (32 cases=48%), followed by C. glabrata (17 cases=26%) and C. parapsilosis (12 cases=18%), a significant production of phospholipase in all strains of C. albicans was detected. Among Candida non-albicans species, the production of this enzyme only occurred in 1/12 strains of C. parapsilosis. The expression acid protease production was detected in 48% of C. albicans and no strains of Candida non-albicans. All species of Candida were susceptible to amphotericin B. The rate of susceptibility to fluconazole was 100% for albicans and C. parapsilosis. Decreased susceptibility to fluconazole was mostly seen with C. glabrata, which was 76.5% susceptible in a dose-dependent manner. The echinocandins showed a good performance for C. albicans, and maintained a good MIC distribution in C. glabrata.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidemia; Female; Gene Expression Regulation, Fungal; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Virulence Factors; Young Adult

There were 71 patients with candidemia in our hospital from November 1, 1993 to October 31, 1999. We investigated the 59 patients from isolated species, route of infection, underlying disorders, risk factors, complications, treatment and prognosis.Candida albicans was the most commonly isolated species (52%), followed by Candida tropicalis (11%). Eighty eight percent of the patients developed candidemia from central venous catheter related infections. The risk factors to candidemia included keeping the catheter in place for more than 5 days, gastrointestinal tract malignancies, postoperative state of gastrointestinal tract surgery, administration of broad-spectrum or combination antibiotics for more than 5 days, and under corticosteroid therapy. About half of the patients (47%) had complications, including endophthalmitis (19 patients, 32%), septic shock (12 patients, 20 %). Mortality rate associated with candidemia was 46%. Mortality rate was lower in 20 patients who were treated with amphotericin B (40%) than in 34 patients treated with only fluconazole (50%), but it was not statistically significant. In order to make an early diagnosis of candidemia, taking blood cultures and ophthalmologic examinations are essential, especially for patients who have those risk factors to candidemia mentioned above. If the patient was suspected of having catheter related infection, the catheter should be removed quickly and the catheter tip should be cultured. Once candidemia is found, ophthalmologic examination and systemic antifungal therapy are needed. Antifungal therapy with Amphotericin B should be used for patients with severe candidemia or with candide-

Topics: Amphotericin B; Antifungal Agents; Candida; Candidemia; Central Venous Catheters; Cross Infection; Fluconazole; Hospitals; Humans; Prognosis; Risk Factors

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Candida; Candidemia; Child; Disk Diffusion Antimicrobial Tests; Female; Fluconazole; Humans; India; Male; Middle Aged; Species Specificity

The aim of this study was to evaluate the incidence of candidaemia, consumption of fluconazole and susceptibility of blood Candida isolates at a tertiary hospital. From January 1999 to September 2006, all candidaemic episodes were identified and available strains were evaluated for the susceptibilities of antifungal agents. Annual defined daily doses of antifungal agents were collected. There had been 909 Candida isolates detected from the bloodstream of 843 patients during the study period. Among them, 740 isolates were available for the susceptibilities of antifungal agents. The incidence density of candidaemia was 28 episodes per 10,000 patient-days. Species distribution of 909 isolates did not vary annually, but varied greatly in the units of the hospital. Candida parapsilosis was the more prominent (30.1%) isolate in the paediatric units, where C. tropicalis and C. glabrata were less common (12.3% and 1.4% respectively). Resistance rates for itraconazole, fluconazole and voriconazole were 6.9%, 3.8% and 3.8% respectively. There were 25 (3.4%) isolates resistant to amphotericin-B. Although fluconazole usage increased over time (r(2) = 0.45; P = 0.07), fluconazole resistance did not increase accordingly (P = 0.33). In our institution in which the incidence of candidaemia was high, fluconazole resistance among blood Candida isolates remained rare.

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candidemia; Drug Utilization; Hospitals; Humans; Incidence; Microbial Sensitivity Tests; Taiwan

Candida parapsilosis former groups II and III have recently been established as independent species, named Candida orthopsilosis and Candida metapsilosis, respectively. We investigated the distribution of C. parapsilosis complex species in 122 isolates from blood and other sources in a southern Spain tertiary-care hospital, and we examined the relationship between species, site of isolation and biofilm positivity. We also evaluated the planktonic MICs and sessile MICs (SMICs) of voriconazole, amphotericin B and anidulafungin. One hundred and eleven isolates (91%) were categorized as C. parapsilosis sensu stricto, whereas ten isolates (8.2%) were categorized as C. orthopsilosis and one (0.8%) as C. metapsilosis. Biofilm positivity was observed in 58.5% (65 of 111) of C. parapsilosis sensu stricto isolates vs. 0% (0 of 11) of C. orthopsilosis and C. metapsilosis isolates (p <0.01). There was no difference in biofilm production among C. parapsilosis sensu stricto isolates from blood and other sources. MIC values showed that all isolates were susceptible to voriconazole and amphotericin B, whereas two isolates (1.8%) of C. parapsilosis sensu stricto were non-susceptible to anidulafungin. However, the MIC₉₀ value of voriconazole was higher (0.125 mg/L) for C. orthopsilosis than for C. parapsilosis sensu stricto (0.03 mg/L). In contrast to planktonic cells, the SMICs show that amphotericin B and anidulafungin are moderately effective against the biofilm of C. parapsilosis sensu stricto, whereas voriconazole is ineffective.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Biofilms; Candida; Candidemia; Drug Resistance, Fungal; Echinocandins; Humans; Microbial Sensitivity Tests; Pyrimidines; Random Amplified Polymorphic DNA Technique; Triazoles; Voriconazole

This study presents data on species distribution and antifungal susceptibility profiles of Candida bloodstream isolates obtained from a Turkish Tertiary Care Hospital during a 4-year period. All hospitalized patients who had ≥ 1 blood culture positive for yeast during their hospital stay from January 2005 through 2009 were included in this study. All isolates were identified to species level using CHROMagar and ID 32 C. Fluconazole and voriconazole antifungal susceptibility testing was performed using the disk diffusion method according to CLSI M44-A. In vitro activity of amphotericin B was determined by the Etest. Of all 166 yeast isolates, C. albicans was the dominant species (34.3%), followed by Candida parapsilosis (28.9%) and C. tropicalis (8.4%). All of the 48 C. parapsilosis strains were identified as C. parapsilosis sensu stricto. Resistance to fluconazole was more common among C. krusei isolates. Voriconazole resistance was absent. One C. lusitaniae strain showed a high amphotericin MIC (4 μg/ml). Our survey indicated an increase of some non-C. albicans Candida species in our hospital while antifungal resistance was uncommon.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Candida; Candidemia; Child; Child, Preschool; Drug Resistance, Fungal; Fluconazole; Hospitals, University; Humans; Infant; Infant, Newborn; Microbial Sensitivity Tests; Pyrimidines; Triazoles; Turkey; Voriconazole

Invasive candidiasis has emerged as an important nosocomial infection, causing significant morbidity and mortality especially among critically ill patients. The aim of our study was to determine specie distribution and resistance profiles of Candida species isolated from blood cultures.. We conducted a retrospective study of all episodes of candidemia diagnosed in our laboratory from January 2006 to May 2009. The susceptibility to antifungal agents of all Candida isolates was tested by using a Sensititre(®) YeastOne panel.. A total of 130 Candida isolates were recovered from blood cultures. Candida tropicalis was the most frequent specie (37.7%), followed by C. albicans (22.3%), C. glabrata (19.2%), and C. parapsilosis (12.2%). All the isolates were inhibited by ≤1 μg/ml of amphotericin B and ≤2 μg/ml of caspofungin. For fluconazole, 7.3% of clinical isolates were resistant. It was most active against C. parapsilosis (100% susceptible), C. albicans (95.8% susceptible), and C. tropicalis (94% susceptible). All of the fluconazole-susceptible isolates were susceptible to voriconazole, as were 83.3% of the fluconazole-susceptible-dose-dependent isolates. Among fluconazole-resistant isolates, 85.7% were susceptible to voriconazole.. In our institution, C. tropicalis was the most frequent specie isolated from the bloodstream. Caspofungin had an excellent in vitro activity against Candida isolates and was the drug of choice among fluconazole-resistant isolates.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidemia; Caspofungin; Drug Resistance, Fungal; Echinocandins; Female; Fluconazole; Humans; Lipopeptides; Male; Microbial Sensitivity Tests; Pyrimidines; Retrospective Studies; Triazoles; Tunisia; Voriconazole

In recent years, an evident rise in the frequency of candidaemia caused by non-albicans Candida species has been reported. In this paper we present three cases of clinically manifested candidaemia caused by Candida utilis in neonatal patients hospitalized in the same neonatal intensive care unit within a 6 month period. To the authors' knowledge, only two cases of C. utilis candidaemia have been reported in the literature to date, but neither of these involved newborns. Clinical resolution and elimination of C. utilis from the blood were achieved using liposomal amphotericin B or caspofungin in all patients.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidemia; Caspofungin; Echinocandins; Female; Humans; Infant, Newborn; Lipopeptides; Male; Molecular Typing; Mycological Typing Techniques; Random Amplified Polymorphic DNA Technique; Treatment Outcome

Invasive candidiasis is rare in children after the neonatal period, but can occur in children with (secondary) immunodeficiency with a damaged gastrointestinal or skin barrier, or when receiving antibiotics. A 10-month-old girl was diagnosed as suffering from cystic fibrosis (CF) when showing failure to thrive, pulmonary symptoms and hypoproteinaemia. At that time, Candida albicans was identified from blood culture and treated intravenously with liposomal amphotericin B for 13 days. Six weeks later, the girl presented with osteoarticular infection of the left knee caused by C. albicans. The infection showed insufficient response to therapy with liposomal amphotericin B, but the patient recovered after therapy with fluconazole and flucytosine. Follow-up over 4 years revealed no sequelae. In conclusion, invasive Candida infections may occur in patients with CF, and preventive measures might be considered in patients at risk. In the case of an invasive infection, prolonged treatment with a combination of antifungal drugs may be required.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidemia; Candidiasis, Invasive; Cystic Fibrosis; Female; Fluconazole; Flucytosine; Humans; Infant; Osteoarthritis; Treatment Outcome

Candida bloodstream infection has dramatically increased in the last decade due to the growing number of immunocompromised populations worldwide. In this study, we evaluated the antifungal susceptibility profiles and virulence attributes of Candida bloodstream isolates (CBIs) derived from Hong Kong and Finland, information which are vital for devising empirical clinical strategies. Susceptibility testing of a wide range of antifungals including fluconazole, itraconazole, voriconazole, ketoconazole, 5-fluorocytosine, amphotericin B and caspofungin was performed. Haemolytic activity and secretion of proteinase of CBIs were also examined. All CBIs derived from Hong Kong were susceptible to all the antifungals tested whilst some CBIs from Finland were resistant to azoles and caspofungin. C. albicans, C. glabrata and C. tropicalis showed higher haemolytic activity whereas C. parapsilosis and C. guilliermondii were non-haemolytic in general. Proteinase activity of the Finland C. albicans isolates was significantly higher than the Hong Kong isolates. Our data provide a glimpse of the possible evolutionary changes in pathogenic potential of Candida that may be occurring in different regions of the world. Therefore, continuous surveillance and availability of local data should be taken into consideration when treating candidemia patients.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidemia; Caspofungin; Drug Resistance, Fungal; Echinocandins; Finland; Fluconazole; Flucytosine; Hemolysin Proteins; Hong Kong; Humans; Itraconazole; Ketoconazole; Lipopeptides; Microbial Sensitivity Tests; Peptide Hydrolases; Pyrimidines; Triazoles; Virulence Factors; Voriconazole

Topics: Administration, Inhalation; Aged; Amphotericin B; Anti-Asthmatic Agents; Asthma; Candidemia; Candidiasis, Oral; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Fungal; Female; Fluconazole; Glucocorticoids; Humans; Nystatin; Risk Factors