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Reduced Antifungal Susceptibility of Vulvovaginal Candida Species at Normal Vaginal pH Levels

Clinical Implications

Spitzer, Mark MD1; Wiederhold, Nathan P. PharmD2

Journal of Lower Genital Tract Disease: April 2018 - Volume 22 - Issue 2 - p 152–158
doi: 10.1097/LGT.0000000000000383
Original Research Articles: Vagina and Vulva

Objective The aims of the study were to assess for differences in antifungal in vitro potency at pH 7 and pH 4 and to discuss any potential clinical implications of that difference.

Materials and Methods A retrospective analysis of 217 first positive yeast cultures from 217 patients. Yeast isolates underwent antifungal susceptibility testing, with minimum inhibitory concentrations (MICs) (microgram per milliliter) measured at pH 7 and pH 4 for fluconazole, itraconazole, miconazole, clotrimazole, terconazole, and nystatin. Only the first isolates collected from each patient were included in the analysis.

Results Yeast first isolates included 173 Candida albicans, 15 Candida glabrata, and 29 isolates from 8 other species. Geometric mean (GM) MIC values for all antifungals were significantly higher when tested at pH 4 (p < .001 for all comparisons). For C. albicans, the largest GM MIC differences were observed for terconazole (0.17 pH 7 vs 6.17 pH 4) and clotrimazole (0.04 vs 0.24). For terconazole, 97.7% of the isolates had a MIC of 1 or less at pH 7 but 83.2% had a MIC of 4 or higher at pH 4. For C. glabrata, terconazole (GM MIC = 0.26 pH 7 vs >64 pH 4), clotrimazole (0.13 vs 6.96), miconazole (0.06 vs 0.76), and fluconazole (3.17 vs 26.6) were most affected. All C. glabrata isolates had a MIC of 1 or less for terconazole at pH 7 and one had a MIC of 8 at pH 4, whereas all the rest were highly resistant (MIC > 64).

Conclusions Antifungals have reduced in vitro potency when tested at lower pH. Candida glabrata is more affected than C. albicans. The impact may be greatest for the antifungal terconazole and against C. glabrata isolates.

1Department of Obstetrics and Gynecology, Hofstra Northwell School of Medicine, Hempstead, NY; and 2Departments of Pathology & Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio, San Antonio, TX

Reprint requests to: Mark Spitzer, MD, Center for Colposcopy, 1991 Marcus Avenue, STE M215, Lake Success, NY 11042. E-mail:

The authors have declared they have no conflicts of interest.

Copyright © 2018 by the American Society for Colposcopy and Cervical Pathology