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Study Objective: Echinocandins are guideline-preferred therapies for invasive candidiasis (IC). Fixed dosing of echinocandins is commonly used despite variations in body mass index and echinocandin susceptibility. The purpose of this study was to evaluate clinical outcomes of micafungin based on population-predicted pharmacokinetic/pharmacodynamic (PK/PD) factors and susceptibility., Design and Setting: Candida isolate results were screened from bloodstream or intraabdominal cultures of hospitalized patients admitted to a quaternary-care teaching hospital. Patients with a first episode of IC who received micafungin for at least 48 h were included. Patients with mixed cultures or Candida species with no minimum inhibitory concentration (MIC) differences were excluded. Breakpoints for micafungin MIC and area under the curve (AUC)/MIC ratio were calculated using classification and regression tree (CART) analysis and related to clinical outcomes. Primary efficacy outcome was candida-contributable mortality, defined as mortality within 28 days of positive culture with concomitant micafungin treatment failure; secondary outcome was micafungin treatment failure within 28 days, MAIN RESULTS: Seventy-two patients were included of whom 15 (21%) had Candida-contributable mortality and 34 (47%) experienced micafungin treatment failure. C. albicans and C. tropicalis did not have differing MICs and these patients were excluded from the study. Mortality using a CART-derived MIC breakpoint of ≥1.0 mg/L was 38% compared to 9% in patients infected with lower MIC strains (p = 0.003). Patients with a CART-derived AUC/MIC value >138.5 had a mortality rate of 9% compared to 41% for patients with AUC/MIC values below the breakpoint (p = 0.0013). Results were similar for treatment failure rates, and both were confirmed using multivariable models., Conclusions: CART-derived micafungin MIC and AUC/MIC breakpoints predicted patient mortality and treatment failure for certain Candida species. These results support the need for further PK/PD studies to optimize echinocandin dosing and improve patient outcomes., (© 2023 Pharmacotherapy Publications, Inc.)

Objectives: Candida auris is an emerging, often MDR, yeast pathogen. Efficient animal models are needed to study its pathogenicity and treatment. Therefore, we developed a C. auris fruit fly infection model., Methods: TollI-RXA/Tollr632 female flies were infected with 10 different C. auris strains from the CDC Antimicrobial Resistance bank panel. We used three clinical Candida albicans strains as controls. For drug protection assays, fly survival was assessed along with measurement of fungal burden (cfu/g tissue) and histopathology in C. auris-infected flies fed with fluconazole- or posaconazole-containing food., Results: Despite slower in vitro growth, all 10 C. auris isolates caused significantly greater mortality than C. albicans in infected flies, with >80% of C. auris-infected flies dying by day 7 post-infection (versus 67% with C. albicans, P < 0.001-0.005). Comparison of C. auris isolates from different geographical clades revealed more rapid in vitro growth of South American isolates and greater virulence in infected flies, whereas the aggregative capacity of C. auris strains had minimal impact on their growth and pathogenicity. Survival protection and decreased fungal burden of fluconazole- or posaconazole-fed flies infected with two C. auris strains were in line with the isolates' disparate in vitro azole susceptibility. High reproducibility of survival curves for both non-treated and antifungal-treated infected flies was seen, with coefficients of variation of 0.00-0.31 for 7 day mortality., Conclusions: Toll-deficient flies could provide a fast, reliable and inexpensive model to study pathogenesis and drug activity in C. auris candidiasis., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The T2Candida assay is a novel, non-culture-based assay for the diagnosis of candidemia directly from whole blood. The impact of antifungals on the performance of the T2Candida assay and blood culture bottles has not been well described. In this study, the performance of the T2Candida assay was compared to that of blood culture in detecting Candida spp. in spiked blood cultures with or without the presence of antifungals. Clinical bloodstream isolates of Candida spp. were inoculated into human whole blood at low (1 to 5 cells/ml) and high (10 to 50 cells/ml) concentrations with or without the presence of caspofungin and fluconazole. Time to detection (TTD) was assessed for prepared samples using BacT/Alert FA aerobic blood culture bottles or the T2Candida assay. In the absence of antifungals, T2Candida assay sensitivity was comparable to that of blood culture at both the low inoculum and the high inoculum (95% versus 97.5% and 100% versus 100%, respectively) and the assay had an average TTD that was significantly shorter (5.1 h versus 27.2 to 30 h, respectively). Neither caspofungin nor fluconazole was observed to impact the sensitivity or TTD of the T2Candida assay, while fluconazole reduced the overall blood culture sensitivity by 7.5% to 12.5% (at the low inoculum and high inoculum, respectively) and significantly increased the TTD of Candida albicans , C. tropicalis , and C. parapsilosis by 14.8 to 67 h. Neither caspofungin nor fluconazole impacted the performance of the T2Candida assay in vitro , and the assay may be useful for the diagnosis of candidemia in patients receiving antifungal therapy., (Copyright © 2018 American Society for Microbiology.)

This study aimed to describe factors and outcomes associated with Candida colonization of critically ill patients. This was a cross-sectional study conducted over 2 weeks in the intensive care unit (ICU) of a tertiary care hospital at the Texas Medical Center, Houston, TX. All Candida samples were prospectively collected with demographic and clinical data collected retrospectively. We examined 48 patients, 32 (67%) were colonized with Candida spp; 25 (52.1%) patients were isolated with Candida albicans and 18 (37.5%) were isolated with a non-albicans species, mostly commonly Candida glabrata. A multivariate analysis identified proton pump inhibitor administration at admission to ICU [odds ratio 5.66; 95% confidence interval 1.12-28.5] as associated with colonization. Patients colonized with Candida had a significantly longer length of ICU and hospital stays (7.6 ± 6.6 vs. 4.2 ± 2.6 days, P = 0.01 and 14.9 ± 12.9 vs. 7.5 ± 6.7 days, P = 0.02, respectively). Clonality testing between C. albicans and C. glabrata strains identified indistinguishable strains among the patient cohort. These data provide additional information on Candida colonization in critically ill patients.

As a delay in the diagnosis and treatment of candidemia is associated with increased mortality and healthcare costs, a more rapid method of detection is urgently needed. The T2Candida assay is a new rapid diagnostic test, which uses T2 magnetic resonance technology to identify Candida spp. directly from whole blood in approximately 3 hours. In this study, the performance of the BACTEC 9050 using Aerobic Plus/F blood culture bottles was compared to that of the T2Candida assay run on the T2Dx Instrument for detection of Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei, in seeded blood samples at concentrations between 3.1 and 11 CFU/mL. The BACTEC 9050 detected Candida growth in 100% of bottles (n = 20 replicates) within 5 days for all species (63.23 ± 30.27 hours), with the exception of Candida glabrata (0%). The T2Candida assay had a 100% detection rate for each species (n = 13-20 replicates) within 3 hours including C. glabrata. The sensitivity and specificity of the T2Candida assay were 1 and 0.978, respectively., (© 2013.)

Objectives: 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., Methods: 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., Results and Conclusions: 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.

Objective: To summarize published data regarding mechanisms of reduced echinocandin susceptibility in Candida spp., the impact of echinocandin resistance on the fitness and virulence of Candida isolates, and current and future treatment approaches., Data Sources: A search of MEDLINE databases (1966-September 2011) was conducted., Study Selection and Data Extraction: Databases were searched using the terms echinocandin, resistance, and Candida. Citations from publications were reviewed for additional references., Data Synthesis: Echinocandins have in vitro activity against most Candida spp. and are first-line agents in the treatment of candidemia. However, case reports describing echinocandin treatment failure due to resistant isolates have been published. Reduced echinocandin susceptibility has been shown to occur via 3 main mechanisms: (1) adaptive stress responses, which result in elevated cell wall chitin content and paradoxical growth in vitro at supra minimum inhibitory concentrations (MICs); (2) acquired FKS mutations, which confer reduced glucan synthase sensitivity, elevated MICs, and are associated with clinical failure; and (3) intrinsic FKS mutations, which are naturally occurring mutations in C. parapsilosis and C. guilliermondii, which confer elevated MIC levels but a lower level of reduced glucan synthase sensitivity compared with acquired FKS mutations. Some FKS mutants have been shown to have significantly reduced fitness and virulence versus wild type isolates and may contribute to the low incidence of echinocandin resistance reported in large surveillance studies. Treatment strategies evaluated for FKS mutants include echinocandin dose escalation and combination with agents such as calcineurin inhibitors, HSP90 inhibitors, and chitin synthase inhibitors., Conclusions: While the incidence of echinocandin resistance in Candida spp. is low, it can present a significant therapeutic challenge, especially in multidrug-resistant Candida isolates. Dose escalation is unlikely to be effective in treating FKS mutant isolates, and significant adverse effects limit the clinical use of agents evaluated as combination therapy. Patients with infections failing to respond to echinocandin therapy should undergo susceptibility testing and be treated with an alternative antifungal agent if possible.