Activities of E1210 and Comparator Agents Tested by CLSI and EUCAST Broth Microdilution Methods against Fusarium and Scedosporium Species Identified Using Molecular Methods

Abstract

ABSTRACTFusarium(n= 67) andScedosporium(n= 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species ofFusarium(4 isolates unspeciated) and 28Scedosporium apiospermum, 7Scedosporium aurantiacum, and 28Scedosporium prolificansspecies were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC90values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, forFusariumof 0.12, >16, >16, >8, >8, 8, and 4 μg/ml. E1210 was very potent against theScedosporiumspp. tested. The E1210 MEC90was 0.12 μg/ml forS. apiospermum, but 1 to >8 μg/ml for other tested agents. AgainstS. aurantiacum, the MEC50for E1210 was 0.06 μg/ml versus 0.5 to >8 μg/ml for the comparators. AgainstS. prolificans, the MEC90for E1210 was only 0.12 μg/ml, compared to >4 μg/ml for amphotericin B and >8 μg/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; ±2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole andF. oxysporumspecies complex (SC) (60%), posaconazole andS. aurantiacum(85.7%), and voriconazole andS. aurantiacum(85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B-resistant strains ofFusariumspp. andScedosporiumspp. Furthermore,in vitrosusceptibility testing of E1210 against isolates ofFusariumandScedosporiummay be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results.