| Abstrakt: |
ABSTRACTE1210 is a first-in-class broad-spectrum antifungal that suppresses hyphal growth by inhibiting fungal glycophosphatidylinositol (GPI) biosynthesis. In the present study, we extend these findings by examining the activity of E1210 and comparator antifungal agents against Aspergillusspp. by using the methods of the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST) to test wild-type (WT) as well as amphotericin B (AMB)-resistant (-R) and azole-R strains (as determined by CLSI methods). Seventy-eight clinical isolates of Aspergilluswere tested including 20 isolates of Aspergillus flavusspecies complex (SC), 22 of A. fumigatusSC, 13 of A. nigerSC, and 23 of A. terreusSC. The collection included 15 AMB-R (MIC, ≥2 μg/ml) isolates of A. terreusSC and 10 itraconazole-R (MIC, ≥4 μg/ml) isolates of A. fumigatusSC (7 isolates), A. nigerSC (2 isolates), and A. terreusSC (1 isolate). Comparator antifungal agents included anidulafungin, caspofungin, amphotericin B, itraconazole, posaconzole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparators. The essential agreement (EA; ±2 log2dilution steps) was 100% for all comparisons with the exception of posaconazole versus A. terreusSC (EA = 91.3%). The minimum effective concentration (MEC)/MIC90values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, and voriconazole, respectively, were as follows for each species: for A. flavusSC, 0.03, ≤0.008, 0.12, 1, 1, and 1; for A. fumigatusSC, 0.06, 0.015, 0.12, >8, 1, and 4; for A. nigerSC, 0.015, 0.03, 0.12, 4, 1, and 2; and for A. terreusSC, 0.06, 0.015, 0.12, 1, 0.5, and 1. E1210 was very active against AMB-R strains of A. terreusSC (MEC range, 0.015 to 0.06 μg/ml) and itraconazole-R strains of A. fumigatusSC (MEC range, 0.03 to 0.12 μg/ml), A. nigerSC (MEC, 0.008 μg/ml), and A. terreusSC (MEC, 0.015 μg/ml). In conclusion, E1210 was a very potent and broad-spectrum antifungal agent regardless of in vitromethod applied, with excellent activity against AMB-R and itraconazole-R strains of Aspergillusspp. |
