Repurposing the Veterinary Antiprotozoal Drug Ronidazole for the Treatment of Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) is a principal cause of hospital-acquired infections and fatalities worldwide. The need for new, more potent anticlostridial agents is far from being met. Drug repurposing can be utilized as a rapid and cost-efficient method of drug development. The current study was conducted to evaluate the activity of ronidazole, a veterinary antiprotozoal drug, as a potential treatment for CDI. Ronidazole inhibited the growth of clinical C. difficile isolates (including NAP1 and toxigenic strains) at a very low concentration (0.125 µg/mL) and showed superior killing kinetics compared with metronidazole, an anticlostridial agent from the same chemical category. In addition, ronidazole did not inhibit growth of several commensal organisms naturally present in the human intestine that play a protective role in preventing CDIs. Furthermore, ronidazole was found to be non-toxic to human gut cells and permeated a monolayer of colonic epithelial cells (Caco-2) at a slower rate than metronidazole. Finally, ronidazole outperformed metronidazole when both were tested at a dose of 1 mg/kg daily in a mouse model of CDI. Overall, ronidazole merits further investigation as a potential treatment for CDIs.