In vitro activities of the tetrazole VT-1161 compared with itraconazole and fluconazole against Cryptococcus and non- albicans Candida species

Recently, Cryptococcus and non-albicans Candida (NAC) have emerged as health-threatening pathogens for clinical fungal infections. Due to their increased resistance to existing antifungal drugs, novel antifungals are urgently needed. In this study, we evaluated the antifungal effect of VT-1161 and its comparators itraconazole and fluconazole against common fluconazole-sensitive or -resistant Cryptococcus and NAC strains. The tested strains were obtained from Chinese patients by the Invasive Fungal Infection Group within the past 2 years. The minimum inhibitory concentrations (MICs) of VT-1161 and other triazoles were measured according to the Clinical and Laboratory Standards Institute (CLSI) M27-Ed4 guidelines. We found that VT-1161 exhibited strong in vitro activity against Cryptococcus spp.. VT-1161 (geometric mean MIC = 0.024 μg/mL) was 21.7-fold and 104.5-fold more potent than itraconazole and fluconazole, respectively. Against the seven Cryptococcus neoformans isolates with higher fluconazole MICs (≥8 μg/mL based on the MIC₉₀ value of this azole), VT-1161 maintained potent activities, with MICs ranging between 0.031 and 0.5 μg/mL. For NAC spp., VT-1161 (geometric mean MIC = 0.099 μg/mL) was 6.0-fold and 11.4-fold more effective than itraconazole and fluconazole, respectively. There is a positive correlation of the MICs between VT-1161 and itraconazole/fluconazole. The MIC values of VT-1161 against Candida glabrata and Candida tropicalis were significantly lower than those of fluconazole, whereas for Candida parapsilosis the differences in the MIC values between VT-1161 and fluconazole were not statistically significant. The results showed that tetrazole VT-1161 might be a promising candidate for treating Cryptococcus and NAC infections.