Synergistic postantifungal effect of flucytosine and fluconazole onCandida albicans

Abstract

The in vitro efficacy of flucytosine and fluconazole, separately and in combination, with respect to induction of a postantifungal effect (PAFE) on Candida albicans was studied. PAFE refers to the persistent suppression of fungal cell growth following a short period of exposure to an antifungal agent. A turbidometric method was used to measure cell growth and to quantitate the PAFE following exposure of C. albicans yeast cells to different concentrations of the two agents for 2 h. The PAFE was determined by the difference in time (h) required for growth of the control and test cultures to increase to the 0.5 absorbance level following removal of the drug by dilution. Minimum (MIC) and fractional inhibitory concentration determinations were made and the data used for selecting the concentrations used in the PAFE evaluations. A synergistic interaction of the two drugs at concentrations well below their individual MICs was evidenced. Flucytosine:fluconazole ratios of 1:16-1:32 at concentrations ranging from 0.024-0.098 micrograms ml-1 and from 0.78-1.56 micrograms ml-1, with flucytosine and fluconazole, respectively, induced PAFEs which persisted for 2.5 h longer than those achieved when each of the two agents was assayed separately.