Synergisic effects of terbinafine combined with fluconazole or itraconazole on stable fluconazole-resistant Candida albicans induced by fluconazole in vitro
To investigate the effects of terbinafine combined with fluconazole or itraconazole on stable fluconazole-resistant Candida albicans induced by fluconazole in vitro. Methods Eleven flueonazole-sensitive isolates were serially subcultured in YEPD medium containing different concentrations of fluconazole to induce stable fluconazole-resistant strains (MIC≥128 μg/ml). The checkerboard microdilution method was applied according to M27-A to study the interaction of terbinafine with fluconazole or itraconazole against stable fluconazole-resistant strains in vitro. Nucleotide sequence of the encoded region in ERG11 genes of stable fluconazole resistant strains was examined. Results Resistant strains were induced by fluconazole in 11 fluconazole-sensitive isolates but most were not stable. Mutations were detected in the nucleotide sequence of the encoded region in ERG11 of the stable drug acquired resistant isolates. The synergy in terbinafine-fluconazale or itraconazole interaction was observed in stable drug acquired resistant isolates. Conclusion The combinations of terbinafine and fluconazole or itraconazole can show synergisic an-tifungal effects on fluconazole-resistant mutants.