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In Vitro Evaluation of Antifungal Drug Combinations against Multidrug-Resistant Candida auris Isolates from New York Outbreak.

ABSTRACT: Since 2016, New York hospitals and health care facilities have faced an unprecedented outbreak of the pathogenic yeast Candida auris We tested over 1,000 C. auris isolates from affected facilities and found high resistance to fluconazole (MIC?>?256?mg/liter) and variable resistance to other antifungal drugs. Therefore, we tested if two-drug combinations are effective in vitro against multidrug-resistant C. auris Broth microdilution antifungal combination plates were custom manufactured by TREK Diagnostic System. We used 100% inhibition endpoints for the drug combination as reported earlier for the intra- and interlaboratory agreements against Candida species. The results were derived from 12,960 readings, for 15 C. auris isolates tested against 864 two-drug antifungal combinations for nine antifungal drugs. Flucytosine (5FC) at 1.0?mg/liter potentiated the most combinations. For nine C. auris isolates resistant to amphotericin B (AMB; MIC???2.0?mg/liter), AMB-5FC (0.25/1.0?mg/liter) yielded 100% inhibition. Six C. auris isolates resistant to three echinocandins (anidulafungin [AFG], MIC???4.0?mg/liter; caspofungin [CAS], MIC???2.0?mg/liter; and micafungin [MFG], MIC???4.0?mg/liter) were 100% inhibited by AFG-5FC and CAS-5FC (0.0078/1?mg/liter) and MFG-5FC (0.12/1?mg/liter). None of the combinations were effective for C. auris 18-1 and 18-13 (fluconazole [FLC]?>?256?mg/liter, 5FC?>?32?mg/liter) except MFG-5FC (0.1/0.06?mg/liter). Thirteen isolates with a high voriconazole (VRC) MIC (>2?mg/liter) were 100% inhibited by the VRC-5FC (0.015/1?mg/liter). The simplified two-drug combination susceptibility test format would permit laboratories to provide clinicians and public health experts with additional data to manage multidrug-resistant C. auris.

SUBMITTER: O'Brien B

PROVIDER: S-EPMC7179280 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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In Vitro Evaluation of Antifungal Drug Combinations against Multidrug-Resistant Candida auris Isolates from New York Outbreak.

O'Brien Brittany B Chaturvedi Sudha S Chaturvedi Vishnu V

Antimicrobial agents and chemotherapy 20200324 4

Since 2016, New York hospitals and health care facilities have faced an unprecedented outbreak of the pathogenic yeast Candida auris We tested over 1,000 C. auris isolates from affected facilities and found high resistance to fluconazole (MIC > 256 mg/liter) and variable resistance to other antifungal drugs. Therefore, we tested if two-drug combinations are effective in vitro against multidrug-resistant C. auris Broth microdilution antifungal combination plates were c ...[more]

PMID: 31932367

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

Dataset Information

In Vitro Evaluation of Antifungal Drug Combinations against Multidrug-Resistant Candida auris Isolates from New York Outbreak.

Publications

<i>In Vitro</i> Evaluation of Antifungal Drug Combinations against Multidrug-Resistant Candida auris Isolates from New York Outbreak.

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