Bedaquiline and delamanid in the treatment of multidrug-resistant tuberculosis: Promising but challenging
Bedaquiline and delamanid in the treatment of multidrug-resistant tuberculosis: Promising but challenging
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DOI：
10.1002/ddr.21498
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发表时间：
2019-02-01
影响因子：
3.8
通讯作者：
Zhang, Wenhong
中科院分区：
文献类型：
--
作者：
Li, Yang;Sun, Feng;Zhang, Wenhong
改善耐多药结核病（MDR-TB）的治疗结果在一定程度上受到有效抗结核药物不足的阻碍。贝达喹啉和德拉马尼的开发有可能改变耐多药结核病的治疗前景。本文就新型抗结核药物的研究进展作一综述。我们回顾了已发表的旨在评价贝达喹啉和德拉马尼临床疗效和有效性的研究。关于贝达喹啉的5项前瞻性临床研究和7项回顾性研究表明，接受含贝达喹啉方案治疗的患者具有较高的培养转化率（范围为65%至100%）和令人满意的治疗结局。与利奈唑胺联合使用可能会增加贝达喹啉的有效性。关于贝达喹啉耐药性的争议进行了讨论。三项临床试验报告了delamanid的结果，并显示将delamanid引入背景方案可将2个月时的培养转化率从29.6%提高到40%以上。在接受delamanid超过6个月的患者中也观察到更高的有利治疗率，但对照组中约有四分之一的患者违约。总结了7项回顾性研究，并发现了治疗获益。迫切需要来自随机临床试验的更可靠的证据来报告治疗结果，以支持使用delamanid的强烈建议。贝达喹啉和delamanid联合使用的进展也进行了审查，并结合可能是耐受性良好，但需要心电图监测。
Improving treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) is partly hampered by inadequate effective antitubercular agents. Development of bedaquiline and delamanid has potentially changed the treatment landscape for MDR-TB. This review provides an update on the progress of these novel antitubercular agents. We review published studies aimed at evaluating clinical efficacy and effectiveness of bedaquiline and delamanid. Five prospective clinical studies and seven retrospective studies on bedaquiline showed that patients treated with a bedaquiline-containing regimen had a high culture conversion rate ranging from 65 to 100% and a satisfactory treatment outcome. The combined use with linezolid might add to the effectiveness of bedaquiline. Controversies about bedaquiline resistance are discussed. Three clinical trials have reported outcomes on delamanid and showed that introducing delamanid to a background regimen improved culture conversion rate at 2 months from 29.6% to more than 40%. A higher favorable treatment rate was also observed among patients who received delamanid for more than 6 months, but about a quarter of patients defaulted in the control group. Seven retrospective studies were summarized and found a treatment benefit as well. More reliable evidence from randomized clinical trials reporting on the treatment outcomes is needed urgently to support a strong recommendation for the use of delamanid. Advances in the combined use of bedaquiline and delamanid are also reviewed, and the combination may be well tolerated but requires electrocardiograph monitoring.