Antifungal Activity of Geldanamycin Alone or in Combination with Fluconazole Against Candida species

A standardized broth microdilution method was used to test the antifungal activity of geldanamycin (GA), an inhibitor of heat shock protein 90 (Hsp90), alone or in combination with the antifungal agent fluconazole (FLC) against 32 clinical isolates of Candida spp. In addition, a disk diffusion test was also used to evaluate the antifungal effect of these two drugs against Candida spp. by measuring the inhibition zone diameters. We found that the range of minimal inhibitory concentrations (MICs) for GA alone against Candida spp. was 3.2-12.8 mg/L and the geometric mean of MICs was 6.54 mg/L. In addition, the combination of GA with FLC showed synergistic effects in vitro against 2 FLC-susceptible and 6 FLC-resistant isolates of C. albicans. As for the other isolates, indifference but no antagonism was observed. In the disk diffusion assay, the diameter of inhibition zones for FLC combined with GA against FLC-resistant C. albicans isolates was 30 mm, while no inhibition was observed with FLC alone. These results demonstrate that GA possesses antifungal activity against Candida spp., and the combination of GA with FLC shows in vitro synergistic activity against some C. albicans isolates, especially those resistant to FLC.