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

Abstract

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. © 2010 Mycological Society of China.