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Concept: Candida krusei

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SCY-078 is an orally bioavailable ß-1,3-glucan synthesis inhibitor (GSI) and the first-in-class of structurally novel triterpine antifungals in clinical development for treating candidemia and invasive candidiasis. In vitro susceptibility by broth micro-dilution, antifungal carry-over, and time-kill dynamics were determined for 3 reference (ATCC) strains (C. albicans 90028, C. parapsilosis 90018, and C. tropicalis 750), a Quality Control (QC) strain (C krusei 6258), and 4 other strains (C. albicans MYA-2732, 64124, 76485 and C.glabrata 90030). Caspofungin (CASP), fluconazole (FLC), and voriconazole (VRC) were comparators. For time-kill experiments, SCY-078 and CASP were evaluated at 0.25, 1, 2, 4, 8, and 16x MIC80, and FLU and VORI were evaluated at 4x MIC80 The time to reach 50%, 90%, and 99.9% growth from starting innoculum was determined. Net change in CFU/mL was used to determine EC50, EC90, and Emax SCY-078 MIC range was between 0.0625 - 1 μg/mL and generally similar to CASP. Antifungal carryover was not observed for SCY-078. SCY-078 was fungicidal against 7 isolates at ≥4x MIC (kill ≥3log10) and achieved a 1.7 log10 reduction in CFUs/mL against C. albicans 90028. CASP behaved similarly against each isolate and achieved a 1.5 log10 reduction in CFUs/mL against C. albicans 90028. Reductions of 50% in CFUs/mL were achieved rapidly (1-2.8 h); fungicidal endpoints were reached at 12.1 - 21.8 h at ≥4x MIC. EC90 was reached at ∼5x MIC at each time point to 24 h. EC50 and EC90 were generally similar (8-24 h). Time-kill behavior of CASP was similar to SCY-078. FLC and VRC were fungistatic. Overall, SCY-078 has primarily fungicidal activity against Candida spp. and behaved comparably to CASP.

Concepts: Candida, Fluconazole, Candida krusei, Antifungals, Fungemia, Antifungal drug, Candida albicans, Candidiasis

28

Candidemia is an important cause of morbidity and mortality. As statins interfere with yeast membrane synthesis, we assessed whether use of statins during candidemia may cause differences in clinical outcomes. A retrospective review of 124 candidemia episodes during 2003-2008 in which all-cause and attributable mortality, length of stay and level of care were compared for patients who received and those who did not receive statins. A total of 124 candidemia events were observed involving 14 patients on statins and 110 without statins. Overall mortality in candidemia cases was 46%, but only 2% was attributed to candidemia. No differences were observed in clinical outcomes for the two groups of patients. During the last 2-year period of our study, there were higher rates of candidemia caused by non-C. albicans Candida spp., particularly those due to C. glabrata and C. parapsilosis. In conclusion, statin use during candidemia did not alter mortality, length of stay, or intensive care requirement of our patients, despite higher rates of non-C. albicans Candida species isolated during the last 2 years of our study.

Concepts: Mortality rate, Retrospective, Candida parapsilosis, Candida krusei, Candida glabrata, Statin, Candidiasis, Candida albicans

28

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.

Concepts: Yeast, Milk, Candida krusei, Gut flora, Ecology, Candida, Candidiasis, Candida albicans

28

Recent studies have shown decreased susceptibility of Candida krusei to amphotericin B (AmB), in addition to its inherent resistance to fluconazole. The susceptibility of C. krusei to AmB was studied in the Parasitology-Mycology laboratory of Grenoble Teaching Hospital, France. Between 2003 and 2011, we analysed 200 C. krusei isolates from 130 patients. The isolates were mainly collected in intensive care, cardio-thoracic and cancer/haematology units. Minimum inhibitory concentrations (MICs) were determined by the E-test method. The modal MIC was 0.5 μg ml(-1) ; the MIC(50) and MIC(90) (MICs encompassing 50% and 90% of all isolates tested, respectively) were 0.5 μg ml(-1) and 1 μg ml(-1) . The Cuzick’s and Kendall’s tests showed a significant increase in MIC values between 2003 and 2011 (P = 0.001 and P ≤ 0.001, respectively), regardless of age or gender. No statistical difference was reached with these tests when the first 100 or 50 data were excluded. Despite the increase observed in the first period of the study, our results confirm the low AmB MICs reported in previous studies. However, some authors have recently reported much higher MICs. This discrepancy cannot be explained by method biases and could reflect C. krusei epidemiological differences among populations.

Concepts: Retrospective, Amphotericin B, Hospital, Scientific method, Candida krusei, Cultural studies

5

Candida krusei is a diploid, heterozygous yeast that is an opportunistic fungal pathogen in immunocompromised patients. This species also is utilized for fermenting cocoa beans during chocolate production. One major concern in the clinical setting is the innate resistance of this species to the most commonly used antifungal drug fluconazole. Here we report a high-quality genome sequence and assembly for the first clinical isolate of C. krusei, strain 81-B-5, into 11 scaffolds generated with PacBio sequencing technology. Gene annotation and comparative analysis revealed a unique profile of transporters that could play a role in drug resistance or adaptation to different environments. In addition, we show that while 82% of the genome is highly heterozygous, a 2.0 Mb region of the largest scaffold has undergone loss of heterozygosity. This genome will serve as a reference for further genetic studies of this pathogen.

Concepts: Candida krusei, Organism, Gene, Bacteria, Chocolate, Yeast, Genetics, DNA

3

Blood cultures are approximately 50% sensitive for diagnosing invasive candidiasis. The T2Candida nanodiagnostic panel uses T2 magnetic resonance and a dedicated instrument to detect Candida directly within whole blood samples.

Concepts: Fungal diseases, Immune system, Nuclear magnetic resonance, Candida krusei, Fungemia, Bacteremia, Candida albicans, Candidiasis

3

Candida auris is a multidrug-resistant yeast incriminated in a wide spectrum of invasive infections, especially in intensive care settings. The first draft genome sequence of C. auris, VPCI 479/P/13, from a case with fungemia was sequenced using the Illumina MiSeq platform. The estimated genome size is 12.3 Mb, with 6,675 coding sequences.

Concepts: Human Genome Project, Sequence, DNA, Virus, Candida krusei, Yeast, Genome, Candida albicans

1

Candida krusei bloodstream infection (CK BSI) is associated with high mortality, but whether this is due to underlying comorbidities in affected patients or the organism itself is unknown. Identifying patient characteristics that are associated with CK BSI is crucial for clinical decision-making and prognosis.

Concepts: Virus, Bacteria, Yeast, Candida krusei, Immune system

1

To assess the risk factors and outcomes associated with fungemia caused by the six most commonly occurring Candida species in patients with and without malignancies.

Concepts: Epidemiology, The Canon of Medicine, Candida krusei, Candida albicans, Candidiasis

1

Community-onset candidemia constitute a distinct clinical entity the incidence of which is increasing. Contribution of non-albicans Candida species is rising.

Concepts: Bacteremia, Matrix-assisted laser desorption/ionization, Fungemia, Candida krusei, Candida albicans, Mass spectrometry, Candidiasis