Farnesol, lyticase, and tyrosol against Candida albicans biofilms: Interactions with fluconazole and micafungin

Biofilm-associated reductions in antifungal susceptibility complicate Candida albicans infection management. This in vitro study assessed farnesol, lyticase, and tyrosol, alone and in combination with fluconazole or micafungin, against established C. albicans biofilms. We screened 25 clinical isolates from patients with suspected vulvovaginal candidiasis using crystal violet staining. Sessile minimum inhibitory concentrations (SMICs), defined as ≥80% reductions in metabolic activity, were determined by a tetrazolium reduction assay. Checkerboard interactions were evaluated using fractional inhibitory concentration indices, with upper-bound estimates for fluconazole due to single-agent values reaching the assay ceiling. Twenty-one isolates (84%) formed biofilms. All three compounds alone reduced biofilm metabolic activity. Fluconazole SMICs were ≥64 µg/mL, while micafungin SMICs ranged from 0.5-2 µg/mL. Fluconazole-farnesol and micafungin-farnesol combinations demonstrated synergy in 61.9% and 57.1% of isolates, respectively, with no observed antagonism. Farnesol reduced fluconazole SMICs to 2-8 µg/mL and median micafungin SMICs from 1 to 0.25 µg/mL (Holm-adjusted p < 0.001). Micafungin-lyticase interactions were predominantly indifferent (90.5%). In contrast, tyrosol combinations were antagonistic with fluconazole in 33.3% of isolates and with micafungin in 28.6%. Farnesol combinations consistently exhibited the most potent antibiofilm effects. However, the small sample size, unreplicated biofilm susceptibility assays, and estimated fluconazole interaction indices necessitate cautious interpretation. Future research should investigate reproducibility, safety, and in vivo efficacy.