Objectives: Isavuconazole is a novel triazole in phase III studies for the treatment of fungemia. The antifungal activity of Isavuconazole against pathogenic non-Candida yeasts has been assessed only for a limited number of isolates. In this study we assessed the in vitro activity of Isavuconazole and other triazoles against rare non-Candida yeast isolates.
Methods: Twenty nine non-Candida clinical isolates were studied: Dipodascus capitatus (n=9; 31%), Rhodotorula mucilaginosa (n=2; 6.9%), Saccharomyces cerevisiae (n=15; 51.7%), and Trichosporon spp. (n=3; 10.3%). Isolates were identified by amplifying and sequencing the ITS1–5.8S–ITS2 region. Antifungal activity of Isavuconazole, fluconazole, voriconazole, and posaconazole was determined using the CLSI M27-A3 broth microdilution procedure. In addition, the activity of Isavuconazole was determined using the E-test. For Isavuconazole, each CLSI and corrected (two-fold scale) E-test MIC was further converted to a log2 MIC. The methods agreed when the log2 MIC measured by each was within +/–2 or fewer twofold dilutions of the other.
Results: MIC50s, MIC90s, and MIC range (in μg/ml) for each antifungal was: posaconazole (0.5/2/0.062-2); fluconazole (4/32/1->128); voriconazole (0.125/0.5/0.031-1); Isavuconazole (CLSI: 0.125/0.5/≤0.015-1; E-test: 0.125/1/0.031-2). For Isavuconazole, CLSI M27-A3 and the E-test agreed for 51.7% (+/-1 twofold dilutions) and 75.8% (+/-2 twofold dilutions) of strains. According to the breakpoints (CLSI M27-A3), the strains were classified as follows: fluconazole (susceptible, 72.4%; susceptible–dose dependent, 20.6%; resistant, 6.9%) and voriconazole (susceptible, 100%). No breakpoints are defined for posaconazole and Isavuconazole. The only two strains of R. mucilaginosa showing fluconazole resistance (>128 μg/ml) were voriconazole-susceptible and had MICs for Isavuconazole <=0.125 μg/ml.
Conclusions: All the non-Candida isolates of D. capitatus, R. mucilaginosa, S. cerevisiae, and Trichosporon spp. studied were susceptible to Isavuconazole (MICs <=1 μg/ml), including the fluconazole-resistant strains. The E-test seems a reasonable alternative method for determining the antifungal activity of Isavuconazole against non-Candida isolates.
- ECCMID 20th (2010)