Antifungal susceptibility of Saccharomyces cerevisiae and therapy in a murine model of disseminated infection

Abstract

Background: The incidence of systemic infections by Saccharomyces cerevisiae has increased in recent years, especially among immunocompromised patients. Amphotericin B, voriconazole or echinocandins have been used with favorable outcome against systemic infections by this fungus. However, clinical experience is limited and no in vivo studies have been conducted.

Aims: We evaluated the in vitro activity of nine antifungal compounds against S.cerevisiae and the in vivo efficacy of those three antifungals showing the highest in vitro activity by using a murine model of systemic infection.

Methods: Minimal inhibitory concentrations (MICs) were determined by the microdilution method against three strains of S. cerevisiae. After intravenous infection with 5×10⁷ CFUs, animals received liposomal amphotericin B (5mg/kg), voriconazole (25mg/kg) or anidulafungin (5mg/kg). Treatment efficacy was assessed by determining of CFUs/g in liver, kidney, brain, lung and spleen.

Results: 5-Fluorocytosine was the most in vitro active compound followed by amphotericin B, voriconazole and anidulafungin. The in vivo study showed that liposomal amphotericin B was the most effective drug driving highest fungal clearance.

Conclusions: All treatments reduced the fungal load in comparison to the control group, being liposomal amphotericin B the most effective drug followed by anidulafungin and finally voriconazole.

Keywords: Animal model; Antifungal therapy; Infección sistémica; Modelo animal; Saccharomyces cerevisiae; Sensibilidad; Susceptibility; Systemic infection; Tratamiento antifúngico.