Antifungal Susceptibility of Clinical Isolates and Artificially Produced Multi-azole-resistant Strains of Cryptococcus neoformans (formerly: Cryptococcus grubii) to Ravuconazole.

Ravuconazole (RVCZ) is a newly available human azole drug in Japan since 2018 and is a broad-spectrum antifungal agent that exhibits excellent activity against Candida albicans and Cryptococcus neoformans (formerly: Cryptococcus grubii). The drug is also highly active against isolates that are resistant to fluconazole (FLCZ). In the present study, the in vitro susceptibility to ravuconazole (RVCZ) of Japanese clinical isolates and multi-azole-resistant strains of C. neoformans was investigated using the Clinical & Laboratory Standards Institute (CLSI) M27-A3 test. The minimum inhibitory concentrations for the 14 clinical isolates and the multi-azole-resistant strains were 0.003125-0.125 mg/L and 0.25-0.5 mg/L for RVCZ, respectively. RVCZ is as effective as ITCZ and VRCZ for treating clinical isolates from cats and humans. Moreover, RVCZ is highly effective against multi-azole-resistant strains that encode a protein with a G344S substitution in ERG11. Consequently, RVCZ has considerable potential for use as a therapeutic agent for multi-azole resistant cryptococcosis.