Combination of Amphotericin B and 5-Fluorocytosine
Moderate synergism of fungistasis was demonstrated in all normally sensitive Cryptococcus neoformans and in the partially 5-fluorocytosine (5-FC)-resistant Candida albicans strains. Synergism of the fungicidal effect was found throughout. It was more pronounced in Sabouraud broth than in an antagonist-free medium. In all strains the appearance of 5-FC-resistant mutants was significantly reduced by subinhibitory concentrations of amphotericin B (amph. B).
Survival rate of mice treated with a combination of the two drugs was increased in comparison to that of animals treated with each drug alone, viable fungus cells in the organs being reduced in number. Mycological cure was only achieved by combined therapy.
Attempts were also made to explain the mechanism of synergism. Addition of amph. B was shown to increase incorporation of fluori-nated pyrimidine into RNA of the fungi. Decreased protein synthesis as produced by 5-FC alone was found more pronounced when amph. B was added in concentrations ineffective by themselves.
KeywordsResistant Mutant Concentration Index Cryptococcus Neoformans Subinhibitory Concentration Fungicidal Effect
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