In vitro activities of the tetrazole SHR8008 compared to itraconazole and fluconazole against Candida and Cryptococcus species

Candida and Cryptococcus are the main pathogens of clinical fungal infection associated with high morbidity and mortality. SHR8008 (in fact, this is the only official name in China and it is called VT-1161 by FDA) is a novel tetrazole agent that selectively inhibits fungal CYP51A compared to mammalian cytochrome P450 enzymes to achieve a better antifungal effect. The in vitro activities of SHR8008 and its comparators itraconazole and fluconazole were determined in 127 Candida and 50 Cryptococcus strains isolated from Chinese patients in the last 2 years by Invasive Fungal Infection Group. The MICs of SHR8008 and other triazoles were measured by the Clinical and Laboratory Standards Institute guidelines M27-E4. For Candida spp., SHR8008 (geometric mean MIC=0.078 μg/mL) was 6.5-fold and 11.2-fold more potent than itraconazole and fluconazole, respectively. There is a good correlation of MICs between SHR8008 and itraconazole/fluconazole. The MIC values of SHR8008 against Candida glabrata and Candida tropicalis were significantly lower than those of fluconazole, while for Candida albicans and Candida parapsilosis, the differences between SHR8008 and fluconazole were not statistically significant, either. For Cryptococcus spp., SHR8008 (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 elevated fluconazole MICs (≥8μg/mL based on the MIC90 value for this azole), SHR8008 maintained potent activity, with MICs ranging between 0.031 and 0.5 μg/mL. The results showed that tetrazole SHR8008 was more promising in the treatment of Candida and Cryptococcus infection than itraconazole and fluconazole.