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

doi:10.19982/j.issn.1000-6621.20260390

Abstract

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

CLC Number:

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

Figures/Tables 2

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]

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%

References 72

[1]	World Health Organization. Global tuberculosis report 2025[R]. Geneva: World Health Organization, 2025.
[2]	Geng X, Zhang F, Liu R, et al. Efficacy and safety of treatment regimens for drug-resistant tuberculosis in different regions: a systematic review and meta-analysis[J]. BMC Infect Dis, 2026, 26(1): 361. doi:10.1186/s12879-026-12642-x.
[3]	Conradie F, Diacon A H, Ngubane N, et al. Treatment of Highly Drug-Resistant Pulmonary Tuberculosis[J]. N Engl J Med, 2020, 382(10): 893-902. doi:10.1056/NEJMoa1901814.
[4]	Conradie F, Bagdasaryan T R, Borisov S, et al. Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis[J]. N Engl J Med, 2022, 387(9): 810-823. doi:10.1056/NEJMoa2119430.
[5]	Nyang’wa B T, Berry C, Kazounis E, et al. Short oral regimens for pulmonary rifampicin-resistant tuberculosis (TB-PRACTECAL): an open-label, randomised, controlled, phase 2B-3, multi-arm, multicentre, non-inferiority trial[J]. Lancet Respir Med, 2024, 12(2): 117-128. doi:10.1016/S2213-2600(23)00389-2.
[6]	Conradie F, Badat T, Poswa A, et al. A pragmatic trial of a 6-month strategy for rifampicin-resistant tuberculosis[J]. N Engl J Med, 2026, 394(24): 2429-2439. doi:10.1056/NEJMoa2503687.
[7]	World Health Organization. WHO Consolidated Guidelines on Tuberculosis. Module 4: Treatment-Drug-Resistant Tuberculosis Treatment, 2022 Update[R]. Geneva: World Health Organization, 2022.
[8]	World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: Treatment and care[R]. Geneva: World Health Organization, 2025.
[9]	Wang J, Xue Y, Nie W, et al. Safety and tolerability of contezolid versus linezolid for short-term treatment of rifampicin-resistant pulmonary tuberculosis: a randomized controlled study[J]. Infect Drug Resist, 2025, 18: 3307-3315. doi:10.2147/IDR.S516991. pmid: 40635770
[10]	Wang J, Nie W, Ma L, et al. Clinical utility of contezolid-containing regimens in 25 cases of linezolid-intolerable tuberculosis patients[J]. Infect Drug Resist, 2023, 16: 6237-6245. doi:10.2147/IDR.S425743.
[11]	中国防痨协会, 《中国防痨杂志》编辑委员会, 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, 等. 康替唑胺治疗结核病专家共识[J]. 中国防痨杂志, 2025, 47(2): 123-129. doi:10.19982/j.issn.1000-6621.20240480.
[12]	Andries K, Verhasselt P, Guillemont J, et al. A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis[J]. Science, 2005, 307(5707): 223-227. doi:10.1126/science.1106753. pmid: 15591164
[13]	Centers for Disease Control and Prevention. Provisional CDC guidelines for the use and safety monitoring of bedaquiline fumarate (sirturo) for the treatment of multidrug-resistant tuberculosis[J]. MMWR Recomm Rep, 2013, 62(RR-09): 1-12. pmid: 24157696
[14]	Li R, Ma J B, Yang H, et al. Effects of Bedaquiline Combined with Fluoroquinolone and/or Clofazimine on QT Interval in Patients with Multidrug-Resistant Tuberculosis: a Retrospective Study[J]. Microbiol Spectr, 2023, 11(4): e0104823. doi:10.1128/spectrum.01048-23.
[15]	初乃惠, 李强, 聂文娟, 等. 抗结核药物所致QTc间期延长临床监测和管理专家共识[J]. 中国防痨杂志, 2024, 46(1): 8-17. doi:10.19982/j.issn.1000-6621.20230271.
[16]	Stover C K, Warrener P, VanDevanter D R, et al. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis[J]. Nature, 2000, 405(6789): 962-966. doi:10.1038/35016103.
[17]	Singh R, Manjunatha U, Boshoff H I M, et al. PA-824 Kills Nonreplicating Mycobacterium tuberculosis by Intracellular NO Release[J]. Science, 2008, 322(5906): 1392-1395. doi:10.1126/science.1164571.
[18]	Keam S J. Pretomanid: First Approval[J]. Drugs, 2019, 79(16): 1797-1803. doi:10.1007/s40265-019-01207-9. pmid: 31583606
[19]	Stancil S L, Mirzayev F, Abdel-Rahman S M. Profiling Pretomanid as a Therapeutic Option for TB Infection: Evidence to Date[J]. Drug Des Devel Ther, 2021, 15: 2815-2830. doi:10.2147/DDDT.S281639.
[20]	Matsumoto M, Hashizume H, Tomishige T, et al. OPC-67683, a Nitro-Dihydro-Imidazooxazole Derivative with Promising Action against Tuberculosis In Vitro and In Mice[J]. PLoS Med, 2006, 3(11): e466. doi:10.1371/journal.pmed.0030466. pmid: 17132069
[21]	Ryan N J, Lo J H. Delamanid: First Global Approval[J]. Drugs, 2014, 74(9): 1041-1045. doi:10.1007/s40265-014-0241-5. pmid: 24923253
[22]	Szumowski J D, Lynch J B. Profile of delamanid for the treatment of multidrug-resistant tuberculosis[J]. Drug Des Devel Ther, 2015, 9: 677-682. doi:10.2147/DDDT.S60923.
[23]	Garcia-Prats A J, Frias M, Van Der Laan L, et al. Delamanid Added to an Optimized Background Regimen in Children with Multidrug-Resistant Tuberculosis: Results of a Phase Ⅰ/Ⅱ Clinical Trial[J]. Antimicrob Agents Chemother, 2022, 66(5): e0214421. doi:10.1128/aac.02144-21.
[24]	Swaney S M, Aoki H, Ganoza M C, et al. The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria[J]. Antimicrob Agents Chemother, 1998, 42(12): 3251-3255. doi:10.1128/AAC.42.12.3251. pmid: 9835522
[25]	Imperial M Z, Nedelman J R, Conradie F, et al. Proposed linezolid dosing strategies to minimize adverse events for treatment of extensively drug-resistant tuberculosis[J]. Clin Infect Dis, 2022, 74(10): 1736-1747. doi:10.1093/cid/ciab699.
[26]	Chen T, Li W, Shen F, et al. The structure, properties, and clinical utility of contezolid for antituberculosis: a narrative review[J]. Infect Dis Ther, 2026, 15(1): 43-56. doi:10.1007/s40121-025-01256-6.
[27]	Lechartier B, Cole S T. Mode of action of clofazimine and combination therapy with benzothiazinones against Mycobacterium tuberculosis[J]. Antimicrob Agents Chemother, 2015, 59(8): 4457-4463. doi:10.1128/AAC.00395-15.
[28]	Aldred K J, Blower T R, Kerns R J, et al. Fluoroquinolone interactions with Mycobacterium tuberculosis gyrase: Enhancing drug activity against wild-type and resistant gyrase[J]. Proc Natl Acad Sci U S A, 2016, 113(7): E839-E846. doi:10.1073/pnas.1525055113.
[29]	Shee S, Singh S, Tripathi A, et al. Moxifloxacin-mediated killing of Mycobacterium tuberculosis involves respiratory downshift, reductive stress, and accumulation of reactive oxygen species[J]. Antimicrob Agents Chemother, 2022, 66(9): e0059222. doi:10.1128/aac.00592-22.
[30]	World Health Organization. WHO consolidated guidelines on drug-resistant tuberculosis treatment[R]. Geneva: World Health Organization, 2019.
[31]	初乃惠, 陈效友, 聂文娟, 等. 环丝氨酸治疗结核病的临床用药指南[J]. 中国防痨杂志, 2020, 42(6): 540-547. doi:10.3969/j.issn.1000-6621.2020.06.001.
[32]	Van Deun A, Maug A K J, Salim M A H, et al. Short, Highly Effective, and Inexpensive Standardized Treatment of Multidrug-resistant Tuberculosis[J]. Am J Respir Crit Care Med, 2010, 182(5): 684-692. doi:10.1164/rccm.201001-0077OC.
[33]	Moodley R, Godec T R. Short-course treatment for multidrug-resistant tuberculosis: the STREAM trials[J]. Eur Respir Rev, 2016, 25(139): 29-35. doi:10.1183/16000617.0080-2015. pmid: 26929418
[34]	Nunn A J, Phillips P P J, Meredith S K, et al. A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis[J]. N Engl J Med, 2019, 380(13): 1201-1213. doi:10.1056/NEJMoa1811867.
[35]	Hewison C, Khan U, Bastard M, et al. Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort[J]. Clin Infect Dis, 2022, 75(6): 1006-1013. doi:10.1093/cid/ciac019. pmid: 35028659
[36]	Goodall R L, Meredith S K, Nunn A J, et al. Evaluation of two short standardised regimens for the treatment of rifampicin-resistant tuberculosis (STREAM stage 2): an open-label, multicentre, randomised, non-inferiority trial[J]. Lancet, 2022, 400(10366): 1858-1868. doi:10.1016/S0140-6736(22)02078-5. pmid: 36368336
[37]	World Health Organization. WHO consolidated guidelines on tuberculosis: Module 4: treatment: drug-resistant tuberculosis treatment[R]. Geneva: World Health Organization, 2020.
[38]	Guglielmetti L, Khan U, Velásquez G E, et al. Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis[J]. N Engl J Med, 2025, 392(5): 468-482. doi:10.1056/NEJMoa2400327.
[39]	Song Z, Liu C, He W, et al. Insight into the drug-resistant characteristics and genetic diversity of multidrug-resistant Mycobacterium tuberculosis in China[J]. Microbiol Spectr, 2023, 11(5): e0132423. doi:10.1128/spectrum.01324-23.
[40]	Xia H, Van Den Hof S, Cobelens F, et al. Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China[J]. BMC Infect Dis, 2020, 20(1): 19. doi:10.1186/s12879-020-4758-9.
[41]	Domínguez J, Boeree M J, Cambau E, et al. Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a 2023 TBnet/RESIST-TB consensus statement[J]. Lancet Infect Dis, 2023, 23(4): e122-e137. doi:10.1016/S1473-3099(22)00875-1. pmid: 36868253
[42]	Sun F, Li Y, Zhang Y, et al. A 6- to 9-months oral regimen for rifampicin-resistant tuberculosis: a randomized open-label noninferiority trial in China[J]. Clin Microbiol Infect, 2026, 32(3): 429-439. doi:10.1016/j.cmi.2025.11.015.
[43]	Fu L, Zhang X, Xiong J, et al. Selecting an appropriate all-oral short-course regimen for patients with multidrug-resistant or pre-extensive drug-resistant tuberculosis in China: A multicenter prospective cohort study[J]. Int J Infect Dis, 2023, 135: 101-108. doi:10.1016/j.ijid.2023.08.001. pmid: 37567554
[44]	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, 中国防痨协会, 《中国防痨杂志》编辑委员会. 耐药肺结核全口服化学治疗方案中国专家共识(2021年版)[J]. 中国防痨杂志, 2021, 43(9): 859-866. doi:10.3969/j.issn.1000-6621.2021.09.002.
[45]	中国防痨协会, 《中国防痨杂志》编辑委员会, 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. 耐药结核病全口服短程治疗专家共识[J]. 中国防痨杂志, 2025, 47(7): 830-839. doi:10.19982/j.issn.1000-6621.20250087.
[46]	中华医学会结核病学分会. 中国耐多药/利福平耐药结核病化学治疗指南(2026年版)[J]. 中华结核和呼吸杂志, 2026, 49(6): 623-643. doi:10.3760/cma.j.cn112147-20251104-00674.
[47]	Kwak N, Kim J Y, Han A, et al. Optimal dosing and duration of linezolid for the treatment of multidrug-resistant and rifampicin-resistant tuberculosis: an individual patient data meta-analysis[J]. Eur Respir J, 2025, 66(2): 2500315. doi:10.1183/13993003.00315-2025.
[48]	Zhurkin D, Gurbanova E, Campbell J R, et al. Safety of prolonged treatment with bedaquiline in programmatic conditions[J]. ERJ Open Res, 2022, 8(2): 00685-2021. doi:10.1183/23120541.00685-2021.
[49]	Sutherland H S, Tong A S T, Choi P J, et al. 3,5-dialkoxypyridine analogues of bedaquiline are potent antituberculosis agents with minimal inhibition of the hERG channel[J]. Bioorg Med Chem, 2019, 27(7): 1292-1307. doi:10.1016/j.bmc.2019.02.026.
[50]	Yao R, Wang B, Fu L, et al. Sudapyridine (WX-081), a novel compound against Mycobacterium tuberculosis[J]. Microbiol Spectr, 2022, 10(1): e0247721. doi:10.1128/spectrum.02477-21.
[51]	Guo S, Wang B, Fu L, et al. In Vitro and In Vivo Activity of Oxazolidinone Candidate OTB-658 against Mycobacterium tuberculosis[J]. Antimicrob Agents Chemother, 2021, 65(11): e0097421. doi:10.1128/AAC.00974-21.
[52]	Crowley B M, Boshoff H I, Boving A, et al. Discovery and development of a new oxazolidinone with reduced toxicity for the treatment of tuberculosis[J]. Nat Med, 2026, 32(2): 553-560. doi:10.1038/s41591-025-04164-x.
[53]	Li S Y, Converse P J, Betoudji F, et al. Next-generation diarylquinolines improve sterilizing activity of regimens with pretomanid and the novel oxazolidinone TBI-223 in a mouse tuberculosis model[J]. Antimicrob Agents Chemother, 2023, 67(4): e0003523. doi:10.1128/aac.00035-23.
[54]	Chen R H, Burke A, Cho J G, et al. New oxazolidinones for tuberculosis: are novel treatments on the horizon?[J]. Pharmaceutics, 2024, 16(6): 818-844. doi:10.3390/pharmaceutics16060818.
[55]	Diacon A H, Barry C E, Carlton A, et al. A first-in-class leucyl-tRNA synthetase inhibitor, ganfeborole, for rifampicin-susceptible tuberculosis: a phase 2a open-label, randomized trial[J]. Nat Med, 2024, 30(3): 896-904. doi:10.1038/s41591-024-02829-7. pmid: 38365949
[56]	Luo W, Huang Z, Xu D, et al. Discovery and preclinical evaluations of JBD0131, a novel nitrodihydro-imidazooxazole anti-tuberculosis agent[J]. Bioorg Med Chem Lett, 2022, 72: 128871. doi:10.1016/j.bmcl.2022.128871.
[57]	Tahlan K, Wilson R, Kastrinsky D B, et al. SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis[J]. Antimicrob Agents Chemother, 2012, 56(4): 1797-1809. doi:10.1128/AAC.05708-11.
[58]	Lu Y, Zheng M, Wang B, et al. Clofazimine analogs with efficacy against experimental tuberculosis and reduced potential for accumulation[J]. Antimicrob Agents Chemother, 2011, 55(11): 5185-5193. doi:10.1128/AAC.00699-11. pmid: 21844321
[59]	Makarov V, Manina G, Mikusova K, et al. Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis[J]. Science, 2009, 324(5928): 801-804. doi:10.1126/science.1171583. pmid: 19299584
[60]	Makarov V, Lechartier B, Zhang M, et al. Towards a new combination therapy for tuberculosis with next generation benzothiazinones[J]. EMBO Mol Med, 2014, 6(3): 372-383. doi:10.1002/emmm.201303575. pmid: 24500695
[61]	Shirude P S, Shandil R K, Manjunatha M R, et al. Lead optimization of 1,4-azaindoles as antimycobacterial agents[J]. J Med Chem, 2014, 57(13): 5728-5737. doi:10.1021/jm500571f. pmid: 24874895
[62]	Hariguchi N, Chen X, Hayashi Y, et al. OPC-167832, a novel carbostyril derivative with potent antituberculosis activity as a DprE1 inhibitor[J]. Antimicrob Agents Chemother, 2020, 64(6): e0202019. doi:10.1128/AAC.02020-19.
[63]	Xu M, Zhang L, Wang B, et al. In vitro and in vivo activities of a novel benzothiopyranone candidate NTB-3119M against Mycobacterium tuberculosis[J]. Tuberculosis, 2025, 154: 102654. doi:10.1016/j.tube.2025.102654.
[64]	Nuermberger E L, Martínez-Martínez M S, Sanz O, et al. GSK2556286 is a novel antitubercular drug candidate effective In Vivo with the potential to shorten tuberculosis treatment[J]. Antimicrob Agents Chemother, 2022, 66(6): e0013222. doi:10.1128/aac.00132-22.
[65]	Wilburn K M, Montague C R, Qin B, et al. Pharmacological and genetic activation of cAMP synthesis disrupts cholesterol utilization in Mycobacterium tuberculosis[J]. PLOS Pathog, 2022, 18(2): e1009862. doi:10.1371/journal.ppat.1009862.
[66]	De Jager V R, Dawson R, Van Niekerk C, et al. Telacebec (Q203), a new antituberculosis agent[J]. N Engl J Med, 2020, 382(13): 1280-1281. doi:10.1056/NEJMc1913327.
[67]	Poulton N C, Azadian Z A, DeJesus M A, et al. Mutations in rv0678 confer low-level resistance to benzothiazinone DprE1 inhibitors in Mycobacterium tuberculosis[J]. Antimicrob Agents Chemother, 2022, 66(9): e0090422. doi:10.1128/aac.00904-22.
[68]	Almeida D V, Converse P J, Nuermberger E L. Mutations in Rv0678 reduce susceptibility of Mycobacterium tuberculosis to the DprE1 inhibitor TBA-7371[J]. Antimicrob Agents Chemother, 2023, 67(3):e0005223. doi:10.1128/aac.00052-23.
[69]	Kilinç G, Saris A, Ottenhoff T H M, et al. Host-directed therapy to combat mycobacterial infections[J]. Immunol Rev, 2021, 301(1): 62-83. doi:10.1111/imr.12951. pmid: 33565103
[70]	Tian N, Chu H, Li Q, et al. Host-directed therapy for tuberculosis[J]. Eur J Med Res, 2025, 30(1): 267. doi:10.1186/s40001-025-02443-4. pmid: 40211397
[71]	Fu L, Xiong J, Wang H, et al. Study protocol for safety and efficacy of all-oral shortened regimens for multidrug-resistant tuberculosis: a multicenter randomized withdrawal trial and a single-arm trial [SEAL-MDR][J]. BMC Infect Dis, 2023, 23(1): 834. doi:10.1186/s12879-023-08644-8. pmid: 38012543
[72]	Guo X, Lu J, Li J, et al. The Subunit AEC/BC02 Vaccine Combined with Antibiotics Provides Protection in Mycobacterium tuberculosis-Infected Guinea Pigs[J]. Vaccines, 2022, 10(12): 2164. doi:10.3390/vaccines10122164.