[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
In vitro Evaluation of Antifungal Drug Combinations against Multidrug-resistant Candida auris isolates from New York Outbreak
Brittany O’Brien, Sudha Chaturvedi, Vishnu Chaturvedi
Since 2016, New York hospitals and healthcare facilities have faced an unprecedented outbreak of the pathogenic yeast Candida auris. We tested over one thousand C. auris isolates from affected facilities and found high-resistance to fluconazole (MIC > 256 mg/L), and variable resistance to other antifungal drugs. Therefore, we tested if two-drug combinations are effective in vitro against multidrug-resistant C. auris. Broth micro-dilution 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 inter-laboratory agreements against Candida species. The results were derived from 12,960 readings, for fifteen C. auris isolates tested against 864 two-drug antifungal combinations for nine antifungal drugs. Flucytosine (5FC) at 1.0 mg/L potentiated the most combinations. For nine C. auris isolates resistant to amphotericin B (AMB, MIC ≥ 2.0 mg/L]), AMB/5FC (0.25/1.0 mg/L) yielded 100% inhibition. Six C. auris isolates resistant to three echinocandins (anidulafungin [AFG, MIC ≥ 4.0 mg/L], caspofungin [CAS, MIC ≥ 2.0 mg/L], and micafungin [MFG, MIC ≥ 4.0 mg/L]), were 100% inhibited by AFG/5FC and CAS/5FC (0.0078/1 mg/L), and MFG/5FC (0.12/1 mg/L). None of the combinations were effective for C. auris 18-1 and 18-13 (FLC > 256 mg/L, 5FC > 32 mg/L) except MFG/5FC (0.1/0.006 mg/L). Thirteen isolates with high voriconazole MIC (VRC, > 2 mg/L) were 100% inhibited by the VRC/5FC (0.015/1 mg/L). 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.
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Keywords: Drugs Resistance; Candida auris; USA.