Efficacies of Conventional Antifungals and Complementary and Alternative Medicine as Single or Combination Therapies Against Candida Biofilms in Recurrent Vaginal Candidiasis: An In Vitro Study

Objectives: Recurrent vulvovaginal candidiasis (RVVC) is a difficult-to-treat infection, most likely due to the growth of Candida biofilms on the human vaginal epithelium. We assessed in vitro efficacy of conventional antifungals and complementary and alternative medicine (CAM) used in clinical settings, and sought for Candida biofilm-effective single or combination therapies. Methods: Standard broth microdilution assay and XTT (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) assay were used for antifungal and anti-biofilm efficacies of three conventional antifungals, and selected CAM including boric acid, povidone-iodine, and allicin (garlic extract), against Candida clinical isolates grown at neutral and acidic pHs respectively. Fractional inhibitory concentration (FIC) indices were assessed to evaluate interactions between fluconazole and different CAM. Viable count-based cell enumeration and confocal laser scanning microscopy (CLSM) were performed to confirm the efficacy of single or combination therapies against Candida biofilms. Results: All selected conventional antifungals and CAM showed efficacies against planktonic Candida cells. Acidic vaginal microenvironments provided agent-specific protection to Candida cells against conventional antifungals and the CAM. Synergistic or additive interactions were observed between fluconazole at serum achievable concentrations and povidone-iodide at topically achievable concentrations against all tested Candida strains. Most antifungal agents except caspofungin had very limited activities against Candida biofilms. Combining fluconazole at 8 mg/L with povidone-iodine at 2048 mg/L effectively killed Candida biofilms in an acidic vaginal microenvironment to a level that is comparable to that of caspofungin. Conclusions: We provided robust in vitro evidence supporting the combinational use of oral fluconazole and topical CAM povidone-iodine against Candida biofilms in managing RVVC.