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In-vitro Activity of Avermectins against Mycobacterium ulcerans

机译:阿维菌素抗溃疡分枝杆菌的体外活性

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摘要

Mycobacterium ulcerans causes Buruli ulcer (BU), a debilitating infection of subcutaneous tissue. There is a WHO-recommended antibiotic treatment requiring an 8-week course of streptomycin and rifampicin. This regime has revolutionized the treatment of BU but there are problems that include reliance on daily streptomycin injections and side effects such as ototoxicity. Trials of all-oral treatments for BU show promise but additional drug combinations that make BU treatment safer and shorter would be welcome. Following on from reports that avermectins have activity against Mycobacterium tuberculosis, we tested the in-vitro efficacy of ivermectin and moxidectin on M. ulcerans. We observed minimum inhibitory concentrations of 4–8 μg/ml and time-kill assays using wild type and bioluminescent M. ulcerans showed a significant dose-dependent reduction in M. ulcerans viability over 8-weeks. A synergistic killing-effect with rifampicin was also observed. Avermectins are well tolerated, widely available and inexpensive. Based on our in vitro findings we suggest that avermectins should be further evaluated for the treatment of BU.
机译:溃疡分枝杆菌引起布鲁里溃疡(BU),这是使皮肤下组织衰弱的感染。有一种WHO建议的抗生素治疗方法,需要链霉素和利福平进行8周疗程。该方案彻底改变了BU的治疗方法,但存在的问题包括对链霉素每日注射的依赖以及副作用,例如耳毒性。对BU进行全口服治疗的试验显示出希望,但欢迎使BU治疗更安全,更短的其他药物组合。根据阿维菌素对结核分枝杆菌具有活性的报道,我们测试了伊维菌素和莫西菌素对溃疡性支原体的体外功效。我们观察到最低抑制浓度为4–8μg/ ml,使用野生型和生物发光的溃疡分枝杆菌进行的时间杀灭试验显示,溃疡分枝杆菌的生存能力在8周内显着剂量依赖性降低。还观察到了与利福平的协同杀伤作用。阿维菌素具有良好的耐受性,可广泛获得且便宜。根据我们的体外研究结果,我们建议应进一步评估阿维菌素对BU的治疗。

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