Identification and antifungal susceptibility patterns of reference yeast strains to novel and conventional agents: A comparative study using CLSI, EUCAST and Sensititre YeastOne methods

Objectives: The aim of this study was to identify and determine the MICs of 13 antifungal drugs, including the novel agents ibrexafungerp, manogepix and rezafungin, against 22 laboratory reference strains from 14 different Candida spp. and allied yeast genera using the EUCAST, CLSI and Sensititre™ YeastOne™ (SYO) methods. Results: Complete agreement between molecular and proteomics methods was observed for identification. The compounds with the greatest in vitro activity, as indicated by the lowest geometric mean MIC (GM), were manogepix (GM: 0.01), isavuconazole (GM: 0.05) and rezafungin (GM: 0.03-0.07). The overall essential agreement (EA) (within ±0 to ±2 2-fold dilutions) between the reference methods, EUCAST and CLSI, was 95%, with results ranging from 82% (ibrexafungerp) to 100% (amphotericin B, anidulafungin, fluconazole, 5-flucytosine and micafungin). Regarding EA for EUCAST and CLSI compared with SYO, values were 91% and 89%, respectively. Nevertheless, when the MIC values were transformed into log2, significant differences were observed (e.g. fluconazole, ibrexafungerp and 5-flucytosine). At the species level, Candidozyma auris and Candida duobushaemulonii exhibited the highest number of cases with significant differences when comparing the three techniques for each antifungal. Conclusions: The high EA observed reinforces the reliability of EUCAST, CLSI and SYO in guiding antifungal therapy. However, the differences in EA, particularly for ibrexafungerp and 5-flucytosine, highlight the importance of continued evaluation of these methodologies to ensure consistency. Given that antifungal susceptibility testing plays a critical role in treatment decisions, understanding these variations is essential to prevent potential misclassification of susceptibility profiles, which could impact clinical outcomes.