Post-antifungal effect and effects of sub-MIC concentrations on previously treated Candida spp.: influence of exposure time and concentration

This study evaluates the influence of exposure time and concentration on the post-antifungal effect (PAFE) and the effect of sub-MIC concentrations (1/4 x MIC) on Candida albicans and C. glabrata in the PAFE stage (PAFSE). This stage was induced by pretreatment for 1.5, 3 or 12 h with 1 x, 4 x or 8 x MIC of 4 antifungal agents fundamental to modern candidiasis therapy. The length of the 2 effects studied was dependent on the concentration of the antifungal agent applied during pretreatment, as well as on the exposure time. An increase in the dose and/or longer pretreatment prolonged the duration of the PAFE and PAFSE in both species and with all the antifungal agents. Significant PAFEs were always observed for amphotericin B and 5-fluorocytosine (0.8-13 h and 0.6-10.8 h, respectively). These values were increased (by 2.3-8.7 h and 1.5-7.8 h, respectively) by posterior exposure to 1/4 x MIC of the respective antifungal agent. Neither ketoconazole nor fluconazole were able to induce significant PAFEs, even with exposures of up to 12 h duration and a dose of 8 x MIC. However, treatment with 1/4 x MIC of each of the 2 azoles led to significant PAFSEs in both yeast species, of up to 6.5 h duration with ketoconazole and 1.7 h with fluconazole, if the concentrations and/or exposure times were sufficiently high.