ABSTRACT Sensititre YeastOne (SYO) is a widely used commercial colorimetric assay, yet its performance for C. auris remains uncertain. We tested 113 global isolates, including 24 FKS1 mutants, using SYO and the Clinical and Laboratory Standards Institute (CLSI) broth microdilution in parallel. Agreement (±1 twofold dilution) and categorical agreement (CA) were assessed using Centers for Disease Control and Prevention (CDC) tentative resistance breakpoints, CLSI epidemiological cut-off values (ECVs) where available, and the SYO-specific wild-type upper limit value (WT-ULV) for amphotericin B. CLSI-SYO agreement was poor for posaconazole (18%) and amphotericin B (40%); moderate for echinocandins (42%–58%), voriconazole (53%), and itraconazole (65%); and very good for 5-flucytosine (85%). Minimum inhibitory concentrations (MICs) of fluconazole for most isolates were off-scale, precluding accurate estimation. Using CDC breakpoints, amphotericin B showed 31% CA (69% major errors MaEs), while fluconazole exhibited 95% CA (4% MaEs, 1% very major errors). Applying the SYO WT-ULV for amphotericin B corrected all discrepancies (100% CA). SYO generated higher MICs than CLSI for 5-flucytosine and azoles, with a resistance-like colorimetric phenotype resulting in high azole MICs in 8% of isolates. Up to 25% of FKS1 mutants fell below CLSI ECVs by SYO, whereas 14% of WT isolates were overcalled caspofungin-resistant due to a resistance-like colorimetric phenotype. Applying an adjusted interpretive threshold of 0.25 mg/L for anidulafungin and micafungin, and reading growth inhibition endpoints for caspofungin, eliminated the corresponding errors. SYO reliably detects fluconazole and amphotericin B resistance (using the SYO-specific WT-ULV) but frequently misclassifies echinocandin resistance in C. auris , particularly for caspofungin and FKS1 mutants, underscoring the need for careful interpretation and potential method-specific interpretive thresholds. IMPORTANCE Accurate antifungal susceptibility testing is critical for guiding antifungal therapy and informing infection prevention and antifungal stewardship strategies for Candida ( Candidozyma ) auris . As Sensititre YeastOne (SYO) is a widely used commercial colorimetric assay for antifugnal susceptibility testing of Candida spp., its performance for C. auris was evaluated in 113 global isolates, including 24 FKS1 mutants. SYO reliably detected fluconazole resistance in C. auris at the CDC breakpoint of ≥32 mg/L, while detection of amphotericin B resistance required the SYO-specific wild-type (WT) upper limit value of 8 mg/L. Up to one-quarter of FKS1 mutants were misclassified as WT, whereas caspofungin resistance was overestimaed in 14% of WT isolates using the CLSI epidemiological cutoff values 1 mg/L for anidulafungin, 0.5 mg/L for micafungin and 0.5 mg/L for caspofungin. Caspofungin should not be used as a standalone marker of echinocandin resistance, while anidulafungin and micafungin consistently detected FKS1 mutants using the adjusted interpretive threshold of 0.25 mg/L.
Siopi et al. (Thu,) studied this question.