In Vitro Activity of Isavuconazole versus Opportunistic Fungal Pathogens from Two Mycology Reference Laboratories [PublishAheadOfPrint]

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 moulds collected worldwide.

The 4,856 clinical fungal isolates, including 2351 Candida spp. isolates, 97 non-Candida yeasts, 1,972 Aspergillus spp. isolates, and 361 non-Aspergillus moulds, including 292 Mucorales isolates collected in 2015-2016, were tested using CLSI methods.

The MIC values for isavuconazole versus Aspergillus ranged from 0.06 μg/ml to ≥16 μg/ml. The modal MIC for isavuconazole was 0.5 μg/ml (range 0.25 μg/ml [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 spp. 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 and for 100.0% of C. krusei. Isavuconazole was active against the non-Candida yeasts, including C. 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 moulds. 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.

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