Influence of pH and concentration on the postantifungal effect and on the effects of subMIC concentrations of four antifungal agents on previously treated Candida sp

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 × 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 × 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 × 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 × MIC of the respective antifungal agent. Although ketoconazole and fluconazole were not able to induce significant PAFEs, posterior exposure to 1/4 × 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.