Impact of pH on the Minimum Inhibitory Concentration (MIC) for Antifungal Agents against Different Yeast Strains

To better assess efficacy in serious blood and soft tissue infections, antifungal susceptibility testing is standardized to a neutral pH level of 7. However, these tests may not accurately reflect antifungal activity in the acidic environment of the vagina, contributing to the discrepancy between in vitro and in vivo performance of antifungal agents in the treatment of vulvovaginal candidiasis (VVC). The objective of this study is to explore the effect of acidic pH on the antifungal activity of four different agents. To do this, we compared the minimum inhibitory concentrations (MICs) of miconazole, fluconazole, tioconazole, and terconazole against seven species of yeast in two pH environments (pH of 4.0 and 7.0). Strain-specific MIC values increased for nearly all antifungal agents at a pH of 4.0 as compared with a pH of 7.0. An exception to this trend was tioconazole activity against Saccharomyces cerevisiae, where MIC improved with a lower pH. Of the antifungal agents examined, miconazole had the lowest MICs across almost all strains at either pH. Its MICs against Candida glabrata, Candida parapsilosis, and S. cerevisiae remained relatively stable at the lower pH compared with the other three agents. Thus, the MIC values of antifungal agents against yeast strains are impacted by a decrease in pH, which may account for the inconsistencies in clinical performance when treating VVC. Furthermore, obtaining a vaginal pH and identifying the yeast strain present may have clinical utility in tailoring the selection of antifungal agents to the actual clinical environment.