Turbidometric characterization of the postantifungal effect: comparative studies with amphotericin B, 5-fluorocytosine and miconazole on Candida albicans

The phenomenon of persistent suppression of Candida albicans yeast cell growth after short drug exposures (postantifungal effect, PAFE) was determined by performing comparative studies using different concentrations of 5-fluorocytosine (5-FC), amphotericin B (AMPH) and miconazole (MCZ). An in vitro turbidometric method was used to measure cell growth and to quantitate the PAFE after removal of the drug by dilution following exposure to C. albicans yeast cells for 0.5 h, 1 h or 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 antifungal agent. A PAFE was demonstrated with each agent and generally the length of the PAFE was dependent upon the concentration of the drug and the time of exposure. An exposure time of 0.5 h resulted in PAFEs ranging from 0.6 to 16.7 h with 5-FC, 0 to 16.5 h with AMPH and 0.1 to 14.1 h with MCZ. In most instances exposure of the cells to each drug for 1 or 2 h resulted in slightly longer PAFEs, respectively. Longer PAFEs were induced with lower concentrations of 5-FC as compared to AMPH and MCZ. The data from such PAFE assays may be useful for determining in vivo treatment regimens, since longer PAFEs may allow for intermittent dosing instead of continuous drug administration.