Effects of sertraline hydrochloride and fluconazole combinations on Cryptococcus neoformans and Cryptococcus gattii

Our study evaluated the efficacy of a combination of fluconazole and the psychoactive compound sertraline against strains of Cryptococcus neoformans and Cryptococcus gattii. Using the chequerboard microdilution method based on CLSI M27-A2 guidelines, we determined the susceptibilities of each drug alone and in combination against 40 strains of serotypes A, D and AD in C. neoformans and 13 strains of serotype B C. gattii. The MIC ranged 10.8–43 and 2–64mg/l for sertraline and fluconazole, respectively. No difference in MICSertraline was observed among the serotypes. However, within C. neoformans, a significant difference in MICFluconazole was observed among the serotypes, as follows: AD >A > D (AD being the most resistant). Strains of C. gattii had MICFluconazole not significantly different from those of serotypes A and AD but significantly higher than serotype D. Synergy (FICI ≤ 0.5) was found for 31 strains, while the remaining 22 strains showed no difference. No evidence for antagonistic interaction was observed. Our study suggests the potential utility of fluconazole–sertraline combination therapy for cryptococcal infections.