LAUSR

Ibrexafungerp (SCY-078) is a novel first-in-class antifungal agent targeting the glucan synthase. C. auris is an emerging multidrug resistant species that has caused outbreaks on five continents. We investigated the in vitro activity of ibrexafungerp against C. auris by the EUCAST E.Def 7.3.1 methodology. C. albicans, C. glabrata and anidulafungin, micafungin, amphotericin B, fluconazole, voriconazole and isavuconazole were included as comparators.C. auris reference strains (CBS12372, CBS12373, CBS10913), 122 C. auris, 16 C. albicans and 16 C. glabrata isolates and C. albicans ATCC64548, C. parapsilosis ATCC22019 and C. krusei ATCC6258 QC strains were included. Echinocandin resistant isolates were FKS sequenced. MIC ranges, modal MIC and MIC50 values were determined. Wild-type upper limits (the upper MIC value where the wild-type distribution ends) were determined following EUCAST principles for setting ECOFFs.Nine repetitions of three QC strains and MICs for C. albicans and C. glabrata yielded narrow MIC ranges with modal MICs in agreement with established EUCAST modal MICs confirming a robust test performance. The ibrexafungerp MICs against C. auris isolates displayed a Gaussian distribution with modal MIC (range) 0.5 mg/L (0.06-2 mg/L) suggesting uniform susceptibility. Eight/122 isolates were echinocandin resistant and harboured the S639F Fks1 alteration. All but one were fluconazole resistant and the MIC distributions for voriconazole and isavuconazole were multimodal confirming variable susceptibility.Ibrexafungerp demonstrated promising activity against C. auris including isolates resistant to echinocandins and/or other agents. The MICs were similar to those reported for the CLSI method suggesting a common clinical breakpoint may be appropriate.