In vitro comparative evaluations of the postantifungal effect: synergistic interaction between flucytosine and fluconazole against Candida albicans

In vitro comparative evaluations were performed to study the efficacy of combinations of flucytosine and fluconazole in producing a postantifungal effect (PAFE) on Candida albicans. Initial studies were done to determine MIC, FIC (fractional inhibitory concentration) and optimal PAFE parameters. A turbidometric method was used to measure yeast cell growth following exposure to different concentrations of the two drugs for periods of 0.5, 1 or 2 h at temperatures of 30 degrees C and 37 degrees C. The PAFE was determined by the difference in time (h) required for growth of the control and test cultures to reach the 0.5 absorbance level following removal of the drug by dilution. Ten strains of C. albicans were then assayed (30 degrees C; 2 h exposure time) and a synergistic PAFE was evidenced with the two drugs at concentrations well below their individual MICs. PAFEs ranging from 3.8 to 10.5 h, which persisted for 1.2-2.5 h longer than those achieved with either agent separately, were evidenced when flucytosine and fluconazole were combined (flucytosine: fluconazole ratios of 1:16-1:32) at concentrations ranging from 0.024 to 0.098 micrograms ml-1 and 0.78 to 1.56 micrograms ml-1 respectively. The concentrations of each agent required to produce an optimal PAFE varied according to the C. albicans strain being assayed.