The effect of antifungal drugs in combination on the growth of Candida glabrata in solid and liquid media

Abstract

The effect of drugs in combination on the growth of Candida glabrata was studied in solid medium by demonstration of reduced or enhanced growth, and in liquid medium by determination of interaction indices. Amphotericin B and 5-fluorocytosine showed a synergic effect, while combinations of amphotericin B and miconazole, and miconazole and 5-fluorocytosine exhibited antagonistic effects. In addition, concentration-dependent antagonism was observed amongst combinations of metabolic inhibitors, between inhibitors of sterol biosynthesis (terbinafine, miconazole, ketoconazole, clotrimazole, econazole, fluconazole, itraconazole and amorolfine) and inhibitors of nucleic acid or protein biosynthesis (5-fluorocytosine, 5-fluorouracil, rifampicin and chlortetracycline). This antagonism was strain-specific, occurring with C. glabrata strain 4, Saccharomyces cerevisiae strain 237 and Candida albicans strain 72R, but not with C. albicans strain 6406 or Candida parapsilosis strain 3104.