Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA.
Int J Antimicrob Agents. 2020 Dec;56(6):106188. doi: 10.1016/j.ijantimicag.2020.106188. Epub 2020 Oct 9.
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.
艰难梭菌感染（CDI）是全球范围内导致医院获得性感染和死亡的主要原因。人们迫切需要新的、更有效的抗梭菌药物，但这一需求远未得到满足。药物再利用可以作为一种快速且具有成本效益的药物开发方法。本研究旨在评估罗硝唑（一种兽用抗原生动物药物）作为治疗 CDI 的潜在药物的活性。罗硝唑以非常低的浓度（0.125μg/mL）抑制临床艰难梭菌分离株（包括 NAP1 和产毒株）的生长，与同属化学类别的抗梭菌药物甲硝唑相比，具有优越的杀菌动力学。此外，罗硝唑不会抑制人类肠道中几种共生生物的生长，这些生物在预防 CDI 方面发挥着保护作用。此外，与甲硝唑相比，罗硝唑对人类肠道细胞没有毒性，并且穿过结肠上皮细胞（Caco-2）单层的速度较慢。最后，在 CDI 小鼠模型中，以 1mg/kg 每日剂量测试时，罗硝唑的表现优于甲硝唑。总体而言，罗硝唑作为 CDI 的潜在治疗方法值得进一步研究。
