In vitro susceptibility of 188 clinical and environmental isolates of Aspergillus flavus for the new triazole isavuconazole and seven other antifungal drugs

Recently isavuconazole, an experimental triazole agent. was found to be active against Aspergillus species. As Aspergillus linens is the second-most common Aspergillus species isolated from human infection and the fungus has not been widely tested against the drug, we studied a large collection of clinical (n = 178) and environmental (n = 10) strains of A. flavus against isavuconazole and compared the results with seven other Aspergillus-active antifungal agents (some of them triazoles, others echinocandins or polyene antifungals: voriconazole, posaconazole. itraconazole, caspofungin, anidulafungin, micafungin and amphotericin B) using Clinical and Laboratory Standards Institute methods. Strains with high minimal inhibitory concentrations (MICs) were tested by E-test as well. The strains were collected from two different geographical locations (India and the Netherlands). Three isolates (1.6%) had high MIC (2 mg l(-1) by microbroth dilution and 8 mg l(-1) by E-test) for amphotericin B..1savuconazole showed good activity against A. flavus strains with MIC50 and MIC90 values of 1 mg l(-1). As compared with voriconazole (the drug recommended for primary therapy of aspergillosis), isavuconazole had better activity (99.5% of strains had MIC of <= 1 mg l(-1) for isavuconazole, compared to 74% of strains with same MIC for voriconazole). All strains were, following recently proposed clinical breakpoints, susceptible for the triazoles tested except three strains, which had MICs of 4 mg l(-1) for voriconazole. Testing these strains with high MIC by E-test. gave results of 0.5-2 mg l(-1). Posaconazole had the lowest MIC50 and MIC90 of 0.125 mg l(-1) and 0.25 mg l(-1), respectively. Among echinocandins, 97% of strains had a minimum effective concentration (MEC) of <= 0.5 mg l(-1) for caspofungin. and all strains had a MEC of <= 0.016 mg l(-1) and <= 0.125 mg l(-1) for anidulafungin and micafungin, respectively.