Combination therapy of experimental candidiasis, cryptococcosis, aspergillosis and wangiellosis in mice

Chemotherapy. 1987;33(5):381-95. doi: 10.1159/000238524.

Abstract

Combination pairs of 5-fluorocytosine (5-FC) + itraconazole (Itra), 5-FC + fluconazole (Fluc), and amphotericin B (Amph B) + Itra were administered to mice with experimental candidiasis, cryptococcosis, aspergillosis and wangiellosis with a variety of combination ratios. The life-prolonging effect of the combinations was compared with the effect of each partner administered alone and with a double dosage. Using the U test of Mann and Whitney, the effects of the concentration were classified as synergistic, additive, indifferent or antagonistic; the degree of the interaction was compared with the known effect of Amph B and 5-FC combinations. The combination 5-FC + Itra was definitely synergistic or additive in candidiasis and aspergillosis. The most pronounced synergism occurred in the infection with a 5-FC-resistant strain of Candida albicans. The degree of synergism was the same as with 5-FC + Amph B. In cryptococcosis this combination was indifferent. The combination of 5-FC + Itra merits clinical investigation, especially in candidiasis and aspergillosis. Amph B + Itra was mostly indifferent and weakly antagonistic; the degree of antagonism was significantly weaker than the one observed with Amph B + ketoconazole (Keto). In candidiasis, 5-FC + Fluc was synergistic, but indifferent in cryptococcosis and aspergillosis.

Publication types

  • Comparative Study

MeSH terms

  • Amphotericin B / therapeutic use
  • Animals
  • Antifungal Agents / therapeutic use*
  • Aspergillosis / drug therapy*
  • Candidiasis / drug therapy*
  • Cryptococcosis / drug therapy*
  • Drug Therapy, Combination
  • Exophiala / drug effects
  • Fluconazole
  • Flucytosine / therapeutic use
  • Itraconazole
  • Ketoconazole / analogs & derivatives
  • Ketoconazole / therapeutic use
  • Mice
  • Mycoses / drug therapy*
  • Triazoles / therapeutic use

Substances

  • Antifungal Agents
  • Triazoles
  • Itraconazole
  • Amphotericin B
  • Fluconazole
  • Flucytosine
  • Ketoconazole