Sertraline exhibits in vivo antifungal activity against Candida auris and enhances the effect of voriconazole in combination

Candida auris is a global health threat due to its multidrug-resistant nature, particularly in intensive care units, where outbreaks are associated with high mortality rates. The urgency for alternative effective strategies has led to the exploration of combination therapy and drug repurposing Out of the possible drugs known with a potential antifungal effect, sertraline, a selective serotonin reuptake inhibitor widely used on clinical settings has shown promising results. This study aimed to evaluate the antifungal activity of sertraline and voriconazole alone and in combination in a murine model of candidaemia due to C. auris. Immunosuppressed BALB/c mice were infected via intravenous injection with C. auris and then received experimental treatments intraperitoneally for 7 days. The therapeutic efficacy was assessed by determining fungal tissue burden and animal survival. Sertraline exhibited a dose-dependent decrease in fungal burden, with the kidneys showing the most substantial reduction. Combination therapy of sertraline + voriconazole demonstrated an enhanced antifungal effect compared to the monotherapy of both drugs. As far as we know, this preclinical study is the first to evaluate the antifungal activity of sertraline, alone and in combination with an antifungal, against C. auris, representing a possible promissory option for adjuvant treatment of candidaemia due to this organism. •The dose of 10 mg/kg/day of sertraline showed significative fungal burden reduction in the analyzed organs.•The dose of 10 mg/kg/day of sertraline displayed an evident improvement on survival rates of the immunosuppressed mice.•Sertraline plus voriconazole in combination exhibited a higher antifungal effect compared to monotherapy.