Activity of Ibrexafungerp (SCY-078) against Isolates as Determined by EUCAST Methodology and Comparison with Activity against and and with the Activities of Six Comparator Agents.

Ibrexafungerp (SCY-078) is a novel first-in-class antifungal agent targeting glucan synthase. is an emerging multidrug-resistant species that has caused outbreaks on five continents. We investigated the activity of ibrexafungerp against by applying EUCAST E.Def 7.3.1 methodology. and , as well as anidulafungin, micafungin, amphotericin B, fluconazole, voriconazole, and isavuconazole, were included as comparators. Three reference strains (CBS12372, CBS12373, and CBS10913) and 122 , 16 , and 16 isolates were evaluated. ATCC 64548, ATCC 22019, and ATCC 6258 served as quality control strains. Echinocandin-resistant isolates were sequenced. MIC ranges and modal MIC and MIC values were determined. Wild-type upper limits (the upper MIC value where the wild-type distribution ends) were determined according to EUCAST principles for setting ECOFFs. Nine repetitions of three QC strains and MICs for and yielded narrow MIC ranges with modal MICs in agreement with established EUCAST modal MICs, confirming a robust test performance. The ibrexafungerp MICs against isolates displayed a Gaussian distribution with a modal MIC (range) of 0.5 mg/liter (0.06 to 2 mg/liter), suggesting uniform susceptibility. Of 122 isolates, 8 were echinocandin resistant and harbored 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 , including isolates resistant to echinocandins and/or other agents. The MICs were similar to those reported for the Clinical and Laboratory Standards Institute method, suggesting that a common clinical breakpoint may be appropriate.