In Vitro Activity of Isavuconazole against Opportunistic Fungal Pathogens from Two Mycology Reference Laboratories

Monitoring antifungal susceptibility patterns for new and established antifungal agents seems prudent given the increasing prevalence of uncommon species associated with higher antifungal resistance. We evaluated the activity of isavuconazole against 4,856 invasive yeasts and molds collected worldwide. The 4,856 clinical fungal isolates, including 2,351 Candida species isolates, 97 non-Candida yeasts, 1,972 Aspergillus species isolates, and 361 non-Aspergillus molds, including 292 Mucorales isolates collected in 2015 to 2016, were tested using CLSI methods. The MIC values for isavuconazole versus Aspergillus ranged from 0.06 to ≥16 μg/ml. The modal MIC for isavuconazole was 0.5 μg/ml (range, 0.25 [A. nidulans and A. terreus species complex] to 4 μg/ml [A. calidoustus and A. tubingensis]). Eight A. fumigatus isolates had elevated isavuconazole MIC values at ≥8 μg/ml (non-wild type). Isavuconazole showed comparable activity to itraconazole against the Mucorales. The lowest modal isavuconazole MIC values were seen for Rhizopus spp., R. arrhizus var. arrhizus, and R. microsporus (all 1 μg/ml). Candida species isolates were inhibited by ≤0.25 μg/ml of isavuconazole (range, 96.1% [C. lusitaniae] to 100.0% [C. albicans, C. dubliniensis, C. kefyr, and C. orthopsilosis]). MIC values were ≤1 μg/ml for 95.5% of C. glabrata isolates and 100.0% of C. krusei isolates. Isavuconazole was active against the non-Candida yeasts, including Cryptococcus neoformans (100.0% at ≤0.5 μg/ml). Isavuconazole exhibited excellent activity against most species of Candida and Aspergillus. Isavuconazole was comparable to posaconazole and voriconazole against the less common yeasts and molds. Isavuconazole was generally less active than posaconazole and more active than voriconazole against the 292 Mucorales isolates. We confirm the potentially useful activity of isavuconazole against species of Rhizopus as determined by CLSI methods.