Effect of pH onIn VitroSusceptibility of Candida glabrata and Candida albicans to 11 Antifungal Agents and Implications for Clinical Use

Abstract

ABSTRACTThe treatment of vulvovaginal candidiasis (VVC) due toCandida glabratais challenging, with limited therapeutic options. Unexplained disappointing clinical efficacy has been reported with systemic and topical azole antifungal agents in spite ofin vitrosusceptibility. Given that the vaginal pH of patients with VVC is unchanged at 4 to 4.5, we studied the effect of pH on thein vitroactivity of 11 antifungal agents against 40C. glabrataisolates and compared activity against 15 fluconazole-sensitive and 10 reduced-fluconazole-susceptibilityC. albicansstrains.In vitrosusceptibility to flucytosine, fluconazole, voriconazole, posaconazole, itraconazole, ketoconazole, clotrimazole, miconazole, ciclopirox olamine, amphotericin B, and caspofungin was determined using the CLSI method for yeast susceptibility testing. Test media were buffered to pHs of 7, 6, 5, and 4. Under conditions of reduced pH,C. glabrataisolates remained susceptible to caspofungin and flucytosine; however, there was a dramatic increase in the MIC90for amphotericin B and every azole drug tested. Although susceptible to other azole drugs tested at pH 7,C. albicansstrains with reduced fluconazole susceptibility also demonstrated reduced susceptibility to amphotericin B and all azoles at pH 4. In contrast, fluconazole-sensitiveC. albicansisolates remained susceptible at low pH to azoles, in keeping with clinical observations. In selecting agents for treatment of recurrentC. glabratavaginitis, clinicians should recognize the limitations ofin vitrosusceptibility testing utilizing pH 7.0.