Understanding the role of biofilms in recurrent vulvovaginal candidiasis (RVVC) and their impact on therapy


Background: Vulvovaginal candidiasis (VVC) is a global health problem, affecting up to 75% of healthy women at least once during their lifetime. Although the majority of cases are treated effectively, ~10% of patients encounter treatment failure and complain of more than 4 episodes of VVC per year, defined clinically as recurrent VVC (RVVC). It has been hypothesised that RVVC proves difficult to treat due to the presence of biofilms within the vaginal mucosa, however definitive evidence for this is lacking. Therefore, the role of biofilms in RVVC needs to be evaluated to aid the management of this infection.

Materials/Methods: An anonymised series of high vaginal swabs (HVS, n=300) were obtained from woman reporting VVC, for at least the second time. The causative organism was identified using MALDI-TOF and biofilm formation assessed using crystal violet and metabolic dyes. Antifungal sensitivity testing was performed on planktonic cells and mature (24 h) biofilms, using antifungals currently used clinically (fluconazole, miconazole and clotrimazole) as well as the alternative natural agent carbohydrate-derived fulvic acid (CHD-FA).
Results: Only 71% of isolates were identified as C. albicans, with the remaining isolates including C. glabrata, C. dubliniensis, and C. parapsilosis. Biofilm assessment showed vaginal isolates were able to form differential biofilms regardless of species; with C. albicans isolates eliciting the greatest variation in biomass. Fluconazole, the first line antifungal used to treat VVC, was ineffective against most isolates, with planktonic MIC’s ranging from 1-32g/mL however when this agent was tested against sessile populations the MIC’s ranged from 16->32g/mL. In contrast, the natural agent CHD-FA was shown to be equally effective against both planktonic and sessile cells with an MIC of 0.25%. 
Conclusions:   Biofilm heterogeneity may contribute to the management of VVC infections, as these communities are known to be notoriously recalcitrant to antifungal therapy, and has been shown to correlate with in vitro antifungal therapy. Furthermore, the effectiveness of the natural agent CHD-FA, highlights its potential role to be used in the clinical management of these infections.

2 / Understanding the role of biofilms in recurrent vulvovaginal candidiasis (RVVC) and their impact on therapy