A longitudinal study on fluconazole resistance in Candida albicans vaginal isolates

Abstract

Background: Recurrent vulvovaginal candidiasis (RVVC), despite its worldwide prevalence, has limited treatment options; and a long-term prophylactic regimen utilising fluconazole is the dominant choice. Objectives: An increase in fluconazole resistance is reported, and little information is available about the reversibility of resistance status following the withdrawal of fluconazole. Methods: Repeated antifungal susceptibility tests (ASTs) for fluconazole at a median interval of 3 months between them were evaluated in women with refractory or recurrent VVC patients at the Vaginitis clinic from 2012 to 2021 (10 years) and performed at pH 7 and pH 4.5 using the broth microdilution tests based on the CLSI M27-A4 reference method. Results: Of 38 patients with long-term follow-up with repeat ASTs, 13 patients (13/38, 34.2%) tested at pH 7.0 remained susceptible to fluconazole with MIC ≤2 μg/mL. Nineteen patients (19/38, 50%) remained resistant to fluconazole with MIC ≥8 μg/mL, whereas four (4/38, 10.5%) changed from susceptible to resistant and two (2/38, 5.2%) changed from resistant to susceptible over time. At pH 4.5, among the 37 patients with repeated MIC values, nine (9/37, 24.3%) remained susceptible to fluconazole and 22 (22/37, 59.5%) remained resistant. Three isolates (3/37, 8.1%) changed from susceptible to resistant, while 3 (3/37, 8.1%) changed from resistant to susceptible over time. Conclusion: Fluconazole susceptibility in Candida albicans vaginal isolates obtained longitudinally in women with RVVC remains stable with rare reversal of resistance despite azole avoidance.