Singh Sanjay, Yotsu Rie, Nuremberger Eric, Srivastava Shashikant
Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Texas Health Science Centre at Tyler, Tyler, Texas, USA.
Department of Tropical Medicine and Infectious Disease, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA.
Antimicrob Agents Chemother. 2025 May 7;69(5):e0002925. doi: 10.1128/aac.00029-25. Epub 2025 Mar 26.
Aligned with the World Health Organization's Road Map, there is an unmet need for research to improve the treatment of Buruli ulcer caused by . The repurposing of drugs could speed up new regimen development to treat Buruli ulcer. Using a virulent reporter strain of with intrinsic bioluminescence (MuAL), we compared the minimum inhibitory concentration (MIC) of moxifloxacin, bedaquiline, telacebec, tebipenem, omadacycline, and epetraborole with standard-of-care drugs-rifampin and clarithromycin. We also compared the efficacy (maximal kill or ) and potency (EC or concentration associated with 50% of ) as single and two-drug combinations. The doubling time of MuAL was calculated as 3.66 (95% CI: 3.41-3.93) days. Telacebec had the lowest MIC (0.0000075 mg/L) among the eight drugs tested, followed by rifampicin (0.5 mg/L) and clarithromycin (0.5 mg/L). Epetraborole, telacebec, and moxifloxacin monotherapy at tested concentrations showed higher compared to clarithromycin and rifampicin. In preclinical studies, telacebec combined with rifampicin or epetraborole and epetraborole combinations with moxifloxacin and omadacycline were superior to the rifampin-clarithromycin combination. The MuAL strain is useful in the rapid screening of drugs' efficacy and potency against . We should leverage the progress made in the tuberculosis drug development pipeline to repurpose the drugs for the rapid development of new therapeutic modalities for Buruli ulcer.
与世界卫生组织的路线图一致，对于改善由……引起的布鲁里溃疡的治疗方法的研究仍存在未满足的需求。药物的重新利用可以加快治疗布鲁里溃疡新方案的开发。使用具有内在生物发光特性的毒力报告菌株（MuAL），我们将莫西沙星、贝达喹啉、替拉塞韦、替比培南、奥马环素和依派硼罗与标准治疗药物利福平和克拉霉素的最低抑菌浓度（MIC）进行了比较。我们还比较了单药和两药联合使用时的疗效（最大杀灭率或……）和效力（EC或与50%的……相关的浓度）。计算得出MuAL的倍增时间为3.66（95%置信区间：3.41 - 3.93）天。在所测试的八种药物中，替拉塞韦的MIC最低（0.0000075 mg/L），其次是利福平（0.5 mg/L）和克拉霉素（0.5 mg/L）。在测试浓度下，依派硼罗、替拉塞韦和莫西沙星单药治疗显示出比克拉霉素和利福平更高的……。在临床前研究中，替拉塞韦与利福平联合使用，或依派硼罗与莫西沙星和奥马环素联合使用均优于利福平 - 克拉霉素联合使用。MuAL菌株有助于快速筛选药物对……的疗效和效力。我们应利用结核病药物研发管道中取得的进展，重新利用这些药物以快速开发治疗布鲁里溃疡的新治疗方法。
