Isavuconazole: A new broad-spectrum azole. Part 1: In vitro activity

Triazoles compounds are first-line agents for the treatment of invasive fungal diseases. Isavuconazole is the most recent triazole compound, approved in 2015 by the FDA and the EMA to treat invasive aspergillosis and mucormycosis. We reviewed here the in vitro activity of isavuconazole against a vast spectrum of species. Isavuconazole MICs were evaluated using CLSI, EUCAST or Etest methods, with no significant differences between the technics. Low MIC₅₀ and MIC₉₀ (<1μg/mL) were described for isavuconazole against the majority of Candida spp., except for C. glabrata and C. krusei. In vitro activity against Aspergillus spp. varied according to the species with an overall MIC₉₀ of 1μg/mL ranging from 0.125μg/mL (A. fumigatus) to 16μg/mL (A. niger, A. tubingiensis). As for Aspergillus, the activity of isavuconazole against agents of mucormycosis varies upon genus and species, with an overall MIC₉₀ from 4 (Rhizopus spp.) to 16μg/mL (Rhizomucor spp. and Mucor spp.). Recently, to help detecting non-wild-type isolates, EUCAST committee has proposed ECOFFs values for C. albicans, C. parapsilosis and C. tropicalis (0.03μg/mL), for Aspergillus fumigatus (2μg/mL), A. nidulans (0.25μg/mL), A. terreus (1μg/mL), A. flavus (2μg/mL) and A. niger (4μg/mL). Moreover, clinical breakpoints (susceptible/resistant) were defined for Aspergillus fumigatus (1μg/mL), A. nidulans (0.25μg/mL) and A. terreus (1μg/mL). Using these breakpoints, isavuconazole showed activity against the vast majority of fungi.