Influence of pH and Concentration on the Postantifungal Effect and on the Effects of Sub-MIC Concentrations of 4 Antifungal Agents on Previously Treated Candida spp.

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Abstract
This study investigates the impact of different pH values (5.5 and 7.4) on the postantifungal effect (PAFE) and the effect of sub-MIC concentrations (1/4 x MIC) on C. albicans and C. glabrata in the PAFE stage (PAFSE). The PAFE stage was induced by a 1.5 h pretreatment with different doses (1, 4 and 8 x MIC) of 4 antifungal agents. An increase in the pH and/or an increase in the dose of the antimycotic prolonged the duration of the PAFE induced by amphotericin B or 5-fluorocytosine and the PAFSE induced by all 4 antifungal agents in both species. 5-Fluorocytosine and amphotericin B (except for treatment with 1 x MIC at pH 5.5) induced significant PAFEs (0.5-3.0 h and 1.4-4.8 h, respectively), which were increased (to 0.9-3.2 h and 0.8-3.4 h, respectively) by posterior (PLEASE EXPLAIN WHAT YOU MEAN BY THE WORD "POSTERIOR" HERE) exposure to 1/4 X MIC of the respective antifungal agent. Although ketoconazole and fluconazole were not able to induce significant PAFEs, posterior exposure to 1/4 x MIC of each of these 2 azoles led to significant PAFSEs of up to 2.6 h in both yeast species when the concentrations and pH were high enough.