耐多药/利福平耐药结核病短程治疗方案的研究进展

doi:10.19982/j.issn.1000-6621.20260390

中国防痨杂志 ›› 2026, Vol. 48 ›› Issue (10): 1635-1644.doi: 10.19982/j.issn.1000-6621.20260390

耐多药/利福平耐药结核病短程治疗方案的研究进展

刘书亚¹, 杨丹², 初乃惠², 阮云洲³, 任敬娟⁴, 王倪⁴(), 成诗明⁵()

¹ 重庆市结核病防治所区县防治科, 重庆 400050
² 首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所结核一科, 北京 101149
³ 中国疾病预防控制中心(中国预防医学科学院)结核病预防控制中心耐药防治部, 北京 102206
⁴ 中国疾病预防控制中心(中国预防医学科学院)结核病预防控制中心应用技术部, 北京 102206
⁵ 中国防痨协会, 北京 100101

收稿日期:2026-07-02 出版日期:2026-10-10 发布日期:2026-09-30
通信作者: 王倪,Email:wangni@chinacdc.cn;成诗明,Email:smcheng@163.com
基金资助:
新发突发与重大传染病防控国家科技重大专项(2025ZD01907702);中国防痨协会“全球结核联盟合作项目”(CATA/TBA 20210310HQ7)

Research progress of short-course treatment regimens for multidrug-resistant/rifampicin-resistant tuberculosis

Liu Shuya¹, Yang Dan², Chu Naihui², Ruan Yunzhou³, Ren Jingjuan⁴, Wang Ni⁴(), Cheng Shiming⁵()

¹ Department of District and County, Chongqing Institute of Tuberculosis Control and Prevention, Chongqing 400050, China
² Department Ⅰ of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Institute, Beijing 101149, China
³ Department of Drug-Resistant Tuberculosis Control, National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention (Chinese Academy of Preventive Medicine), Beijing 102206, China
⁴ Department of Applied Technology, National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention (Chinese Academy of Preventive Medicine), Beijing 102206, China
⁵ Chinese Antituberculosis Association, Beijing 100101, China

Received:2026-07-02 Online:2026-10-10 Published:2026-09-30
Contact: Wang Ni, Email: wangni@chinacdc.cn;Cheng Shiming, Email: smcheng@163.com
Supported by:
National Science and Technology Major Project for the Prevention and Control of Emerging and Major Infectious Diseases(2025ZD01907702);Chinese Antituberculosis Association Global Tuberculosis Alliance Cooperation Project(CATA/TBA 20210310HQ7)

摘要/Abstract

摘要：

耐多药/利福平耐药结核病(multidrug-resistant/rifampicin-resistant tuberculosis, MDR/RR-TB)是全球结核病防控面临的重大公共卫生挑战。近年来,以贝达喹啉、德拉马尼、普托马尼为代表的抗结核新药的研发与应用,推动了短程治疗方案取得突破性进展。与传统18~24个月长程治疗方案相比,短程治疗方案在提高治愈率、降低失访率及减少药物不良反应方面优势显著。目前,B-Pa-L-M方案(B:贝达喹啉;Pa:普托马尼;L:利奈唑胺;M:莫西沙星)已被世界卫生组织列为MDR/RR-TB的首选标准化治疗方案,标志着全球MDR/RR-TB治疗已迈入全口服短程治疗新阶段。作者系统综述了抗结核新药研发进展、MDR/RR-TB短程治疗方案的演变历程及关键临床试验证据,并对未来研发方向进行了展望,旨在为优化MDR/RR-TB治疗策略及公共卫生决策提供参考依据。

关键词: 结核, 抗药性, 药物疗法,联合, 抗结核药

Abstract:

Multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) remains a critical public health challenge for global tuberculosis prevention and control. In recent years, the development and clinical application of novel anti-tuberculosis agents, particularly bedaquiline, delamanid, and pretomanid, have brought revolutionary breakthroughs for short-course regimens. Compared with conventional 18-24-month regimens, short-course regimens have demonstrated significant advantages in improving treatment outcomes, reducing loss to follow-up, and lowering drug-related adverse events. The B-Pa-L-M regimen (B: bedaquiline; Pa: pretomanid; L: linezolid; M: moxifloxacin) has now been recommended by the World Health Organization as the preferred standardized treatment regimen for MDR/RR-TB, marking a new era of all-oral short-course treatment. The authors systematically summarize recent advances in the development of novel anti-tuberculosis drugs, outline the evolution of short-course regimens for MDR/RR-TB alongside their pivotal clinical trial evidence, and discuss future research directions. It aims to provide evidence to support the optimization of MDR/RR-TB treatment strategies and public health decision-making.

Key words: Tuberculosis, Drug resistance, Drug therapy, combination, Antitubercular agents

中图分类号:

刘书亚, 杨丹, 初乃惠, 阮云洲, 任敬娟, 王倪, 成诗明. 耐多药/利福平耐药结核病短程治疗方案的研究进展[J]. 中国防痨杂志, 2026, 48(10): 1635-1644. doi: 10.19982/j.issn.1000-6621.20260390

Liu Shuya, Yang Dan, Chu Naihui, Ruan Yunzhou, Ren Jingjuan, Wang Ni, Cheng Shiming. Research progress of short-course treatment regimens for multidrug-resistant/rifampicin-resistant tuberculosis[J]. Chinese Journal of Antituberculosis, 2026, 48(10): 1635-1644. doi: 10.19982/j.issn.1000-6621.20260390

图/表 2

表1

已上市的耐多药/利福平耐药结核病治疗药物的情况

分类	药物名称(缩写)	化学分类	核心作用机制	上市获批情况	临床注意事项
全新研发的抗结核药物	贝达喹啉(Bdq)	二芳基喹啉类	抑制ATP合酶^[12]	2012年FDA加速批准贝达喹啉上市^[13];2016年11月中国NMPA批准上市	警惕QT间期延长等心脏毒性风险,尤其与氯法齐明、德拉马尼、氟喹诺酮类联用时^[14];需通过规范心电监测和联合用药管理控制^[15]
	普托马尼(Pa)	硝基咪唑类	抑制分枝菌酸合成并干扰氧化呼吸链双重作用^[16-17]	2019年8月FDA通过“有限人群用药批准途径”加速获批^[18];2024年中国NMPA批准上市	需规范联合用药,确保治疗有效性与安全性^[19]
	德拉马尼(Dlm)	硝基咪唑类	抑制分枝菌酸合成并干扰氧化呼吸链双重作用^[20]	2014年欧盟、日本获批上市^[21];2018年中国NMPA批准上市	长期用药(6~8个月)获益显著优于短期用药,需规范疗程管理,同时需要注意监测QT间期延长心脏毒性^[22];可以用于体质量>10kg的儿童患者^[23]
老药新用或拓展新的适应证的药物	利奈唑胺(Lzd)	噁唑烷酮类	抑制蛋白质合成^[24]	全球及中国均已获批上市	周围神经病变、骨髓抑制不良反应发生率高;不能耐受者需调整剂量^[25]
	康替唑胺(Czd)	噁唑烷酮类	抑制蛋白质合成	中国已批准用于复杂性皮肤和软组织感染	整体不良事件发生率显著低于利奈唑胺,利奈唑胺相关不良反应换药后90%可缓解/改善^[11,26]
	氯法齐明(Cfz)	吩嗪类	破坏细胞膜稳定性^[27]	全球及中国均已获批上市	需要关注蓄积毒性及皮肤色素沉着,具有QT间期延长风险,尤其与贝达喹啉联用时需密切监测心电图^[14]
	莫西沙星(Mfx)	氟喹诺酮类	抑制DNA旋转酶和氧化呼吸链^[28-29]	全球及中国均已获批上市	需关注耐药及QT间期延长情况^[1,14]
	左氧氟沙星(Lfx)	氟喹诺酮类	抑制DNA旋转酶^[28]	全球及中国均已获批上市	需关注耐药情况^[1]
	环丝氨酸(Cs)	异噁唑酮类	抑制肽聚糖合成	全球及中国均已获批上市	需关注神经系统不良反应,规范剂量管理^[30-31]

表1

表2

耐多药/利福平耐药结核病短程治疗关键研究证据

研究	研究设计	试验与对照方案	核心疗效	安全性结果
孟加拉国研究^[32]	前瞻性观察性队列研究	9~11个月短程方案(4~6Km-Gfx-Pto-Cfz-Z-E-H_h/5Gfx-Cfz-Z-E);无同期对照	良好结局率为87.9%	药物不良反应发生率为47.5%
STREAM第1阶段^[34]	国际多中心、开放标签、随机对照、Ⅲ期临床试验	9~11个月含注射剂短程方案(4~6Km-Mfx-Cfz-E-Z-H_h-Pto/5Mfx-Cfz-E-Z)和20个月长程方案	短程方案与长程方案组132周良好结局率分别为78.8%和79.8%,短程方案达到非劣效	短程方案与长程方案组≥3级不良事件发生率分别为48.2%和45.4%;QT/QTc间期≥500ms者分别占11.0%和6.4%
STREAM第2阶段^[36]	国际多中心、开放标签、随机对照、Ⅲ期临床试验	9个月含贝达喹啉全口服方案(4Bdq-Lfx-Cfz-E-Z-H_h-Pto/5Bdq-Lfx-Cfz-E-Z)、6个月含贝达喹啉并使用8周二线注射剂卡那霉素方案(2Bdq-Lfx-Cfz-Z-Km-H_h/4Bdq-Lfx-Cfz-Z)和9个月含注射剂方案	9个月含贝达喹啉全口服方案与同期对照方案组的76周良好结局率分别为83%和71%;6个月含贝达喹啉方案与同期对照方案组分别为91%和69%;两种试验方案均达到非劣效	9个月含贝达喹啉全口服方案和同期对照方案组的3~4级听力损失率分别为2%和9%;6个月含贝达喹啉组及其同期对照组分别为4%和8%
Nix-TB^[3]	南非多中心、开放标签、Ⅲ期单臂临床试验	6~9B-Pa-L方案;无同期对照	良好结局率为90%	周围神经病变和骨髓抑制发生率分别为81%和48%,主要与高剂量利奈唑胺相关
ZeNix^[4]	国际多中心、部分盲法、随机Ⅲ期临床试验	B-Pa-L方案中利奈唑胺分别采用1200mg×26周、1200mg×9周、600mg×26周和600mg×9周;无标准治疗对照	4组良好结局率分别为93%、89%、91%和84%	利奈唑胺600mg×26周组周围神经病变和骨髓抑制发生率分别为24%和2%,总体安全性更优
TB-PRACTECAL^[5]	国际多中心、开放标签、随机对照、Ⅱ/Ⅲ期临床试验	阶段1评价24周B-Pa-L-M、B-Pa-L-C和B-Pa-L方案;阶段2主要比较24周B-Pa-L-M与36~80周标准治疗方案	B-Pa-L-M方案与标准治疗组72周时的良好结局率分别为88%和59%,B-Pa-L-M方案达到非劣效	B-Pa-L-M方案与标准治疗方案的72周不良结局率分别为12%和41%
BEAT-TB^[6]	南非多中心、开放标签、随机对照、Ⅲ期临床试验	以贝达喹啉、德拉马尼和利奈唑胺为核心,根据氟喹诺酮药敏联合左氧氟沙星和/或氯法齐明的6个月治疗方案和南非当时采用的9个月或更长治疗策略	6个月短程治疗方案与对照组的76周良好结局率分别为86.1%和86.0%,短程方案达到非劣效	6个月短程治疗方案与对照组≥3级不良事件发生率分别为31.2%和37.0%,差异无统计学意义
end-TB^[38]	国际多中心、开放标签、随机对照、Ⅲ期临床试验	5种9个月全口服方案(B-L-M-Z、B-L-Lfx-C-Z、B-D-L-Lfx-Z、D-C-L-Lfx-Z和D-C-M-Z)和研究期间更新的标准治疗方案	B-L-M-Z、B-L-Lfx-C-Z和B-D-L-Lfx-Z良好结局率分别为89.0%、90.4%和85.2%,标准治疗组为80.7%;3种试验方案均达到非劣效	3种方案严重不良事件发生率分别为14.3%、13.1%和15.7%,标准治疗组为16.7%
TB-TRUST^[42]	中国多中心、开放标签、随机对照、Ⅲ期临床试验	6~9Lfx-Lzd-Cs-Cfz±Z全口服方案和9个月含注射剂方案	6~9Lfx-Lzd-Cs-Cfz±Z与对照组的84周良好结局率分别为76.1%和63.7%,短程方案达到非劣效	6~9Lfx-Lzd-Cs-Cfz±Z和对照组≥3级不良事件发生率分别为59.5%和69.1%
MDR-Chin^[43]	中国多中心、前瞻性队列研究	3种9个月全口服方案(Bdq-Lzd-Mfx-Cs-Z、Lzd-Mfx-Cs-Cfz-Z及Bdq-Lzd-Cs-Cfz-Z);无同期对照	治疗结束后随访12个月总体良好结局率为92.9%	3~4级不良事件发生率为48.1%,严重不良事件发生率为7.7%

表2

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耐多药/利福平耐药结核病短程治疗方案的研究进展

Research progress of short-course treatment regimens for multidrug-resistant/rifampicin-resistant tuberculosis

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