Combinations of antifungal and antineoplastic drugs with interactive effects on inhibition of yeast growth.

Interactive effects among antifungal and antineoplastic drugs contributed to toxicities when combinations of these drugs were used to inhibit the growth of five Candida spp. Drug interactions were measured by growth inhibition in both liquid and solid media, by viable cell counts and by examination using scanning electron microscopy. Large cooperative effects on toxicity were demonstrated between some antineoplastic and antifungal drugs. For example, positive cooperativity was seen between the antineoplastic drug 5-fluorouracil and combinations of the antifungal agents amphotericin B and miconazole nitrate. Smaller, and often negative, interactions occurred between the antineoplastic drug cyclophosphamide and antifungal drugs. The levels of drugs required for inhibition in combination drug treatments were critically dependent upon the ratios as well as the absolute concentrations of the drugs tested. Drug combinations were selected which inhibit yeast growth at concentrations far below the individual MIC of the drugs. These combinations may prove of value in clinical treatments of cancer patients infected by Candida.