Repurposing antimalarials: pyrimethamine exhibits superior in vitro activity to metronidazole against Gardnerella while sparing Lactobacillus.

BACKGROUND

Bacterial vaginosis (BV) is associated with significant reproductive health risks and high recurrence rates after standard antibiotic treatment. Sulfadoxine/pyrimethamine, an antimalarial drug, demonstrated unexpected clearance of BV in clinical trials, suggesting potential antimicrobial effects. Drug repurposing, which leverages existing drugs for new therapeutic applications, offers a promising approach to address the challenges of antimicrobial resistance and high recurrence rates in BV.

OBJECTIVE

To determine the in vitro activity of sulfadoxine/pyrimethamine and its components, sulfadoxine and pyrimethamine, on key species associated with BV.

METHODS

Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined for sulfadoxine/pyrimethamine (20:1 ratio), sulfadoxine, pyrimethamine, and standard-of-care antibiotics, metronidazole and clindamycin, against BV-associated species (Gardnerella spp., Fannyhessea vaginae, Prevotella bivia) and Lactobacillus crispatus (vaginal health marker). Gardnerella biofilms were also exposed to sulfadoxine/pyrimethamine, pyrimethamine, or metronidazole, and biofilm biomass and biofilm cells culturability were assessed.

RESULTS

Sulfadoxine had no effect, while pyrimethamine inhibited all Gardnerella strains with MIC values ranging from 0.125 to 4 mg/L, lower than MICs observed for metronidazole (2-128 mg/L). Pyrimethamine also outperformed metronidazole in inhibiting biofilm mass accumulation and reducing biofilm culturable cells in 3/4 Gardnerella strains. Sulfadoxine/pyrimethamine presented lower MICs than metronidazole for 5/8 Gardnerella strains. Sulfadoxine, pyrimethamine, and sulfadoxine/pyrimethamine showed no activity against other BV-associated species or L. crispatus.

CONCLUSIONS

These findings suggest that pyrimethamine (and sulfadoxine/pyrimethamine) could be promising alternative or adjuvant therapies for BV, warranting further clinical trials.