Efficacy of voriconazole in vitro and in invertebrate model of cryptococcosis.

Abstract

Cryptococcosis is a common opportunistic infection in patients with advanced HIV infection and may also affect immunocompetent patients. The available antifungal agents are few and other options are needed for the cryptococcosis treatment. In this work, we first analyzed the virulence of twelve C. neoformans and C. gattii strains assessing capsule thickness, biofilms formation, and survival and morbidity in the invertebrate model of Galleria mellonella and then we evaluated the antifungal activity of voriconazole (VRC) in vitro and in vivo also using G. mellonella. Our results showed that all Cryptococcus spp. isolates were able to produce capsule and biofilms, and were virulent using G. mellonella model. The VRC has inhibitory activity on planktonic cells with MIC values ranging from 0.03 to 0.25 μg/mL on Cryptococcus spp.; and these isolates were more tolerant to fluconazole (ranging from 0.25 to 16 μg/mL), the triazol agent often recommended alone or in combination with amphotericin B in the cryptococcosis therapy. In contrast, mature biofilms were less susceptible to the VRC treatment. The VRC (10 or 20 mg/kg) treatment of infected G. mellonella larvae significantly increased the larval survival when compared to the untreated group for the both Cryptococcus species and significantly decreased the fungal burden and dissemination in the larval tissue. Our findings corroborate with the literature data, supporting the potential use of VRC as an alternative for cryptococcosis treatment. Here, we emphasize the use of G. mellonella larval model as an alternative animal model for studies of antifungal efficacy on mycosis, including cryptococcosis.