Fluconazole and Amphotericin B: Working Together is Better Against Cryptococcus Gattii

N. d. Ribeiro, J. R. A. Santos, D. A. Santos

Author address: 

Univ.e Federal de Minas Gerais - UFMG, belo horizonte, Brazil

Abstract: 

Background: Amphotericin B and fluconazole are the most used antifungals for the treatment of cryptococcosis caused by Cryptococcus gattii, a main pathogen of cryptococcosis in healthy patients. However, there is a controversy regarding the combination of amphotericin B and fluconazole for fungal infections, due potential antagonism. Here, we evaluated the interaction in vivo between fluconazole and amphotericin B against C. gattii. Methods: Six mice per group were inoculated by the intratracheal route with 1 × 106 cells of L27/01C. gattii strain. Fluconazole (15 or 150 mg/kg/day) and amphotericin B (0.5 mg/kg/day) alone or in combination were administered intraperitoneally (i.p.) from one day post-infection. Animals were monitored daily for the survival curve or mice were euthanized 14 or 80 days post-treatment for CFU/ g lungs or brain quantification.Results: All the treatments significantly prolonged the median survival of mice infected. Treatment with 150 mg/kg/day fluconazole alone or in combination with amphotericin B and 15 mg/kg/day fluconazole in combination with amphotericin B improved the median survival of mice treated with antifungals in monotherapy. Animals infected and treated with fluconazole 150 alone or in combination showed significant reduction of Log10 CFU/g in the lungs, but no significant reduction of fungal burden in lungs occurred in other groups. The fungal burden analysis in the brain of mice infected and treated with fluconazole 150 and amphotericin B post 80 days proved to be sterile in comparison to mice treated with fluconazole 150 alone.Conclusions: This study provided new insights into the fluconazole and amphotericin B combination and reinforced a success of interactions between these antifungals.
2016

abstract No: 

SUNDAY-384

Full conference title: 

ASM Microbe 2016
    • ASM microbe 1st (2016)