In Vitro Activities of Terbinafine in Combination with Fluconazole, Itraconazole, Voriconazole, and Posaconazole against Clinical Isolates of Candida glabrata with Decreased Susceptibility to Azoles

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Abstract
A checkerboard microdilution method, performed according to the recommendations of the National Committee for Clinical Laboratory Standards, was used to study the in vitro interaction of terbinafine (TRB) with fluconazole (FLU), itraconazole (ITRA), voriconazole (VRC), and posaconazole (PSZ) in 24 isolates of Candida glabrata with decreased susceptibility to azoles isolated from the oral cavities of human immunodeficiency virus patients. Synergy, defined as a fractional inhibitory concentration index of ≤0.5, was observed in 17% of TRB-FLU interactions, 21% of TRB-ITRA interactions, 33% of TRB-VRC interactions, and 12% of TRB-PSZ interactions. Where synergy was not achieved, there was still a decrease in the MIC of one or both drugs when used in combination. Antagonism was not observed in any drug combination. Clinical studies are warranted to elucidate the potential utility of these combination therapies.