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metronidazole + fluconazole is a combination regimen evaluated by the University of Washington for the prevention of vaginal infections in high-risk populations. Metronidazole is a nitroimidazole antibiotic that acts as a prodrug; it is reduced in anaerobic bacteria to form reactive intermediates that cause DNA strand breakage and inhibit DNA synthesis. Fluconazole is a triazole antifungal that selectively inhibits the fungal enzyme lanosterol 14-alpha-demethylase (CYP51A1), thereby blocking the conversion of lanosterol to ergosterol, an essential component of the fungal cell membrane. This specific combination was studied as a monthly oral prophylaxis (2 grams of metronidazole and 150 mg of fluconazole) in a Phase 3 trial in Mombasa, Kenya, where it demonstrated a significant reduction in the incidence of bacterial vaginosis and an increase in healthy Lactobacillus colonization among HIV-negative female sex workers.
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