In Vitro Synergism of Fluconazole and Baicalein against Clinical Isolates of Candida albicans Resistant to Fluconazole

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In vitro interaction of fluconazole and baicalein (BE) was investigated against 30 fluconazole-resistant clinical isolates of Candida albicans. Synergistic activities were determined using the checkerboard microdilution assay based on the fractional inhibitory concentration indices. Organisms were also tested against the 2 drugs singly and in combination using time–kill methods. Both fluconazole and BE showed weak antifungal activity when tested alone. However, the combination of fluconazole and BE showed strong antifungal activity against most of the fluconazole-resistant isolates tested. The findings of time–kill curves confirmed the interaction. Yeast cells grown in the presence of BE exhibited a reduced extrusion of Rhodamine 6G, which indicates the inhibition of efflux pumps by BE. This novel synergism of fluconazole and BE that can overcome drug-resistance in yeast may prove useful in combined treatment of fungal infections.