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耐多药结核病药物治疗的最新进展。

Update on drug treatments for multidrug resistant tuberculosis.

作者信息

Davies Geraint R, Aston Stephen

机构信息

University of Liverpool, Liverpool, UK.

出版信息

Curr Opin Infect Dis. 2023 Apr 1;36(2):132-139. doi: 10.1097/QCO.0000000000000899. Epub 2023 Jan 18.

Abstract

PURPOSE OF THE REVIEW

To describe important recent developments in the treatment of multidrug resistant tuberculosis (MDR-TB).

RECENT FINDINGS

In the last decade, novel and repurposed antituberculosis drugs have transformed MDR-TB treatment with improved rates of treatment success, better tolerability and safety and reduced duration. As recently as 2016, standard care relied on up to seven drugs for 24 months with treatment success no better than 70%. Seven drug shorter so-called "Bangladesh" style regimens subsequently achieved similar or better results at a duration of 9-12 months but concerns about first-line resistance additional to rifampicin hampered global uptake. After conditional approval in 2012, the novel agent bedaquiline was demonstrated to improve outcomes and reduce mortality when used in longer and shorter regimens, resulting in the replacement of injectable agents. In the last 2 years, clinical trials of all-oral 6-month three or four drug regimens containing bedaquiline, pretomanid and linezolid have shown superior efficacy against both longer and shorter traditional regimens, resulting in major changes in WHO guidance.

SUMMARY

Although some concerns around safety and emergent bedaquiline resistance remain to be fully addressed, 6-month all oral regimens promise to transform the treatment of people with MDR-TB worldwide.

摘要

综述目的

描述耐多药结核病(MDR-TB)治疗方面近期的重要进展。

近期研究结果

在过去十年中,新型和重新利用的抗结核药物改变了耐多药结核病的治疗,治疗成功率提高、耐受性和安全性更好且疗程缩短。就在2016年,标准治疗还依赖多达七种药物,疗程长达24个月,治疗成功率不超过70%。随后所谓的七种药物的较短疗程“孟加拉国”式方案在9至12个月的疗程中取得了相似或更好的效果,但对除利福平之外的一线耐药性的担忧阻碍了其在全球的采用。在2012年有条件获批后,新型药物贝达喹啉在长疗程和短疗程方案中使用时均被证明可改善治疗效果并降低死亡率,从而取代了注射剂。在过去两年中,含贝达喹啉、普瑞玛尼和利奈唑胺的全口服6个月三药或四药方案的临床试验显示,其对传统长疗程和短疗程方案均具有更高疗效,这导致世界卫生组织的指南发生了重大变化。

总结

尽管围绕安全性和新出现的贝达喹啉耐药性的一些担忧仍有待全面解决,但6个月全口服方案有望改变全球耐多药结核病患者的治疗情况。

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