Candidozyma auris susceptibility from Michigan hospitals to manogepix, rezafungin and nine other antifungal agents

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Abstract Background Candidozyma auris (C. auris) is a resistant fungal pathogen with high mortality. Objectives To evaluate the in vitro activity of 11 antifungal agents against C. auris from multiple hospitals. Methods MIC was determined by microdilution testing for amphotericin B, anidulafungin, caspofungin, manogepix, micafungin, rezafungin and five triazoles. Sanger sequencing was performed on one echinocandin resistant isolate. Results There were 84 C. auris isolates from Michigan that were compared with 27 organisms from external sources. Manogepix had the lowest MIC90 (0.03 mg/L). The next most active agent was micafungin. The echinocandins demonstrated a 98.8% susceptibility. A single isolate was found to have a S639F mutation. Amphotericin B demonstrated a 97.6% susceptibility. The MIC90 demonstrated values of ≤0.5 mg/L for isavuconazole, itraconazole and posaconazole. When separating by colonization versus infection isolates, the MIC90 values were identical for all agents, except micafungin, which showed 0.25 versus 0.12 mg/L, respectively. When comparing the reference isolates with Michigan isolates, the MIC90 was identical for echinocandins and manogepix. Differences noted were with amphotericin B, for which 85.2% were susceptible for reference isolates compared to 97.6% from Michigan isolates, and fluconazole, where 25.9% were susceptible for the reference isolates compared with 4.8% from Michigan isolates. Conclusions Manogepix and echinocandins demonstrated the greatest activity against C. auris irrespective of hospital and were like the reference isolates. Amphotericin B demonstrated greater activity compared with published studies. Fluconazole has poor activity; the activity of other triazoles remains unclear.

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