Antifungal Susceptibility of Rare Yeasts Causing Vulvovaginal Candidiasis in the Acidic Vaginal Environment

To investigate the in vitro potency of 13 antifungals against emerging rare yeast species causing vulvovaginal candidiasis (VVC) under the influence of acidic pH.

Antifungal susceptibility was determined according to CLSI M27/M44-ed3 with minor modifications. In total, 42 isolates of rare yeast were isolated from the vaginal samples based on molecular identification, including Saccharomyces cerevisiae (n=18); Clavispora lusitaniae (n=9); Cyberlindnera fabianii (n=4); Kodamaea ohmeri, Candida metapsilosis, and Nakaseomyces bracarensis (n=2 each); and Pichia norvegensis, Kluyveromyces marxianus, Diutina rugosa, Nakaseomyces nivariensis, and Candida africana (n=1 each).

The antifungal agents most affected by a lower pH were terconazole (3 two-fold dilutions higher, MIC >0.5-8 mg/L) for all yeast isolates, followed by amphotericin B (2 two-fold dilutions higher, MIC >2 mg/L) for 93% of isolates, nystatin (2 two-fold dilutions higher, MIC >4-8 mg/L) for 95% of isolates, and micafungin (2 two-fold dilutions higher, MIC >0.125-1 mg/L) for 50% of isolates, compared with those at pH 7.0, indicating a high percentage of low activity against the yeast species. Fluconazole, voriconazole, miconazole, and clotrimazole were the least affected, while anidulafungin, caspofungin, and 5-flucytosine were not affected significantly by pH, showing activity against most rare yeast species at both pH levels. Nakaseomyces bracarensis and N. nivariensis were the species affected most by the lower pH for all seven azoles tested, but they still remained susceptible to azoles.

The noted shift toward rare yeasts could present a challenge to the clinical treatment of VVC. Considering the influence of acidic pH, our results reveal apparently drug-specific and genus-specific trends in antifungal susceptibility. The variability of rare yeasts with regard to antifungal susceptibility at acidic pH warrants further research on this topic.