Research progress on tuberculosis preventive treatment for close contacts of multidrug-resistant tuberculosis patients

doi:10.19982/j.issn.1000-6621.20250299

Abstract

Abstract:

Tuberculosis preventive treatment (TPT) among close contacts of multidrug-resistant tuberculosis (MDR-TB) patients is a critical intervention to reduce their risk of developing active tuberculosis. Early implementation of effective prevention is crucial for protecting individual health and curbing the spread of drug-resistant tuberculosis. Currently, the TPT regimen for close contacts of MDR-TB patients is limited, and there is a lack of evidence in China. Therefore, this review focuses on core issues in the field of TPT for MDR-TB close contacts, including domestic and international guideline recommendations, available drug regimens, and their efficacy and safety based on current research. The aim is to provide scientific references and decision-making support for developing more optimized management strategies for MDR-TB close contacts and safer, more effective short-course preventive regimens in China.

Key words: Tuberculosis, Drug resistance, multiple, bacterial, Protective agents, Therapeutic uses

CLC Number:

Zu Zhipeng, Chen Haiting, Chen Yuanyuan, Nie Wenjuan, Xu Kaijin, Ruan Qiaoling, Liu Zhengwei, Zhou Lin, Wang Xiaomeng, Gao Lei. Research progress on tuberculosis preventive treatment for close contacts of multidrug-resistant tuberculosis patients[J]. Chinese Journal of Antituberculosis, 2025, 47(11): 1528-1534. doi: 10.19982/j.issn.1000-6621.20250299

References 55

[1]	Wulandari DA, Hartati YW, Ibrahim AU, et al. Multidrug-resistant tuberculosis. Clin Chim Acta, 2024, 559: 119701. doi:10.1016/j.cca.2024.119701.
[2]	World Health Organization. Global tuberculosis report 2024. Geneva: World Health Organization, 2024.
[3]	王歆尧, 姜美丽, 庞元捷, 等. 中国结核病疾病负担现状. 中华流行病学杂志, 2024, 45(6): 857-864. doi:10.3760/cma.j.cn112338-20240311-00111.
[4]	Yang C, Sobkowiak B, Naidu V, et al. Phylogeography and transmission of M.tuberculosis in Moldova: A prospective genomic analysis. PLoS Med, 2022, 19(2):e1003933. doi:10.1371/journal.pmed.1003933.
[5]	Zhang Y, Zhou L, Liu ZW, et al. Multidrug-resistant tuberculosis transmission among middle school students in Zhejiang Province, China. Infect Dis Poverty, 2020, 9(1):57. doi:10.1186/s40249-020-00670-x. pmid: 32460836
[6]	Kendall EA, Fofana MO, Dowdy DW. Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis. Lancet Respir Med, 2015, 3(12):963-972. doi:10.1016/S2213-2600(15)00458-0. pmid: 26597127
[7]	Lu X, Jiang Y, Zhang R, et al. Epidemiologic and Bacterial Factors Facilitating Long-Term Transmission of Multidrug-Resistant Tuberculosis in Shanghai, China. Clin Infect Dis, 2025, 18: ciaf313. doi:10.1093/cid/ciaf313.
[8]	Knight GM, McQuaid CF, Dodd PJ, et al. Global burden of latent multidrug-resistant tuberculosis: trends and estimates based on mathematical modelling. Lancet Infect Dis, 2019, 19(8): 903-912. doi:10.1016/S1473-3099(19)30307-X. pmid: 31281059
[9]	Shleider Carnero Canales C, Marquez Cazorla J, Furtado Torres AH, et al. Advances in Diagnostics and Drug Discovery against Resistant and Latent Tuberculosis Infection. Pharmaceutics, 2023, 15(10):2409. doi:10.3390/pharmaceutics15102409.
[10]	Becerra MC, Franke MF, Appleton SC, et al. Tuberculosis in children exposed at home to multidrug-resistant tuberculosis. Pediatr Infect Dis J, 2013, 32(2):115-119. doi:10.1097/INF.0b013e31826f6063. pmid: 22926210
[11]	Marks SM, Mase SR, Morris SB. Systematic Review, Meta-analysis, and Cost-effectiveness of Treatment of Latent Tuberculosis to Reduce Progression to Multidrug-Resistant Tuberculosis. Clin Infect Dis, 2017, 64(12):1670-1677. doi:10.1093/cid/cix208. pmid: 28329197
[12]	World Health Organization. WHO guidelines on the management of latent tuberculosis infection. Geneva: World Health Organization, 2015.
[13]	World Health Organization. Latent Tuberculosis Infection: Updated and Consolidated Guidelines for Programmatic Management. Geneva: World Health Organization, 2018.
[14]	World Health Organization. WHO operational handbook on tuberculosis. Module 1: Prevention Tuberculosis preventive treatment. Geneva: World Health Organization, 2020.
[15]	World Health Organization. Operational Handbook on Tuberculosis. Module 5: Management of Tuberculosis in Children and Adolescents; 1st ed.ed. Geneva: World Health Organization, 2022.
[16]	World Health Organization. Consolidated Guidelines on Tuberculosis. Module 1: Prevention Tuberculosis Preventive Treatment; 2nd ed. Geneva: World Health Organization, 2024.
[17]	徐彩红, 赵雁林. 中国结核病预防性治疗指南. 北京: 人民卫生出版社, 2023.
[18]	Zhang MW, Zhou L, Zhang Y, et al. Treatment outcomes of patients with multidrug and extensively drug-resistant tuberculosis in Zhejiang, China. Eur J Med Res, 2021, 26(1):31. doi:10.1186/s40001-021-00502-0.
[19]	Fox GJ, Nhung NV, Cam Binh N, et al. Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis in Vietnam. N Engl J Med, 2024, 391(24):2304-2314. doi:10.1056/NEJMoa2314325.
[20]	Hesseling AC, Purchase SE, Martinson NA, et al. Levofloxacin Preventive Treatment in Children Exposed to MDR Tuberculosis. N Engl J Med, 2024, 391(24):2315-2326. doi:10.1056/NEJMoa2314318.
[21]	National Library of Medicine. Protecting households on exposure to newly diagnosed index multidrug-resistant tuberculosis patients(PHOENIx MDR-TB)[EB/OL]. [2025-07-20]. https://ClinicalTrials.gov.
[22]	National Library of Medicine. Bedaquiline roll-out evidence in contacts and people living with HIV to prevent TB (BREACH-TB)[EB/OL]. [2025-07-20]. https://ClinicalTrials.gov.
[23]	Täubel J, Prasad K, Rosano G, et al. Effects of the Fluoroquinolones Moxifloxacin and Levofloxacin on the QT Subintervals: Sex Differences in Ventricular Repolarization. J Clin Pharmacol, 2020, 60(3):400-408. doi:10.1002/jcph.1534
[24]	Che Y, Lu Y, Zhu Y, et al. Surveillance of fluoroquinolones resistance in rifampicin-susceptible tuberculosis in eastern China with whole-genome sequencing-based approach. Front Microbiol, 2024, 15:1413618. doi:10.3389/fmicb.2024.1413618.
[25]	Song Z, Liu C, He W, et al. Insight into the drug-resistant characteristics and genetic diversity of multidrug-resistant Mycobacterium tuberculosis in China. Microbiol Spectr, 2023, 11(5):e0132423. doi:10.1128/spectrum.01324-23.
[26]	Baker JJ, Nahar R, Petroelje BK, et al. Fluoroquinolone-resistant latent tuberculosis infection: A literature review and case series of 5 patients treated with linezolid monotherapy. J Clin Tuberc Other Mycobact Dis, 2023, 32:100376. doi:10.1016/j.jctube.2023.100376.
[27]	Lewis JM, Sloan DJ. The role of delamanid in the treatment of drug-resistant tuberculosis. Ther Clin Risk Manag, 2015, 11:779-791. doi:10.2147/TCRM.S71076.
[28]	孙玙贤, 舒薇, 刘宇红. 贝达喹啉和德拉马尼治疗耐多药结核病对心电图QT间期影响的研究进展. 中华结核和呼吸杂志, 2023, 46(3): 290-294. doi:10.3760/cma.j.cn112147-20220809-00666.
[29]	World Health Organization. Guidelines for the programmatic management of drug-resistant tuberculosis: 2020 update. Geneva: World Health Organization, 2020.
[30]	Hatami H, Sotgiu G, Bostanghadiri N, et al. Bedaquiline-containing regimens and multidrug-resistant tuberculosis: a systematic review and meta-analysis. J Bras Pneumol, 2022, 48(2):e20210384. doi:10.36416/1806-3756/e20210384.
[31]	Liu Y, Matsumoto M, Ishida H, et al. Delamanid: From discovery to its use for pulmonary multidrug-resistant tuberculosis (MDR-TB). Tuberculosis (Edinb), 2018, 111: 20-30. doi:10.1016/j.tube.2018.04.008.
[32]	王乐乐, 杨松. 德拉马尼治疗MDR/XDR-TB的研究进展. 中华临床感染病杂志, 2020, 13(4): 315-320. doi:10.3760/cma.j.issn.1674-2397.2020.04.012.
[33]	Wen S, Jing W, Zhang T, et al. Comparison of in vitro activity of the nitroimidazoles delamanid and pretomanid against multidrug-resistant and extensively drug-resistant tuberculosis. Eur J Clin Microbiol Infect Dis, 2019, 38(7):1293-1296. doi:10.1007/s10096-019-03551-w.
[34]	Pang Y, Zong Z, Huo F, et al. In Vitro Drug Susceptibility of Bedaquiline, Delamanid, Linezolid, Clofazimine, Moxifloxacin, and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in Beijing, China. Antimicrob Agents Chemother, 2017, 61(10):e00900-17. doi:10.1128/AAC.00900-17.
[35]	中华医学会结核病学分会. 抗结核新药贝达喹啉临床应用专家共识(2020年更新版). 中华结核和呼吸杂志, 2021, 44(2): 81-87. doi:10.3760/cma.j.cn112147-20200714-00805.
[36]	Afifi M, Amin W, Helal D, et al. Impact of bedaquiline regimen on the treatment success rates of multidrug-resistant tuberculosis patients in Egypt. Sci Rep, 2024, 14(1):16247. doi:10.1038/s41598-024-65063-8. pmid: 39009633
[37]	Li J, Yang G, Cai Q, et al. Safety, efficacy, and serum concentration monitoring of bedaquiline in Chinese patients with multidrug-resistant tuberculosis. Int J Infect Dis, 2021, 110:179-186. doi:10.1016/j.ijid.2021.07.038. pmid: 34293490
[38]	Chahine EB, Karaoui LR, Mansour H. Bedaquiline: a novel diarylquinoline for multidrug-resistant tuberculosis. Ann Pharmacother, 2014, 48(1):107-115. doi:10.1177/1060028013504087. pmid: 24259600
[39]	Chen Q, Huang T, Zou L, et al. Clinical outcomes of multidrug-resistant tracheobronchial tuberculosis receiving anti-tuberculosis regimens containing bedaquiline or delamanid. Sci Rep, 2024, 14(1):17347. doi:10.1038/s41598-024-68550-0. pmid: 39069547
[40]	Chihota V, Gombe M, Gupta A, et al. Tuberculosis Preventive Treatment in High TB-Burden Settings: A State-of-the-Art Review. Drugs, 2025, 85(2):127-147. doi:10.1007/s40265-024-02131-3. pmid: 39733063
[41]	Isralls S, Baisley K, Ngam E, et al. QT Interval Prolongation in People Treated With Bedaquiline for Drug-Resistant Tuberculosis Under Programmatic Conditions: A Retrospective Cohort Study. Open Forum Infect Dis, 2021, 8(8):ofab413. doi:10.1093/ofid/ofab413.
[42]	Borisov SE, Dheda K, Enwerem M, et al. Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: a multicentre study. Eur Respir J, 2017, 49(5):1700387. doi:10.1183/13993003.00387-2017.
[43]	Mallick JS, Nair P, Abbew ET, et al. Acquired bedaquiline resistance during the treatment of drug-resistant tuberculosis: a systematic review. JAC Antimicrob Resist, 2022, 4(2):dlac029. doi:10.1093/jacamr/dlac029.
[44]	Nguyen TVA, Anthony RM, Bañuls AL, et al. Bedaquiline Resistance: Its Emergence, Mechanism, and Prevention. Clin Infect Dis, 2018, 66(10):1625-1630. doi:10.1093/cid/cix992. pmid: 29126225
[45]	Drusano GL, Myrick J, Maynard M, et al. Linezolid Kills Acid-Phase and Nonreplicative-Persister-Phase Mycobacterium tuberculosis in a Hollow-Fiber Infection Model. Antimicrob Agents Chemother, 2018, 62(8):e00221-18. doi:10.1128/AAC.00221-18.
[46]	Soriano A, Miró O, Mensa J. Mitochondrial toxicity associated with linezolid. N Engl J Med, 2005, 353(21):2305-2306. doi:10.1056/NEJM200511243532123.
[47]	Nahid P, Mase SR, Migliori GB, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med, 2019, 200(10): e93-e142. doi:10.1164/rccm.201909-1874ST.
[48]	Lan Z, Ahmad N, Baghaei P, et al. Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet Respir Med, 2020, 8(4):383-394. doi:10.1016/S2213-2600(20)30047-3. pmid: 32192585
[49]	Padmapriyadarsini C, Oswal VS, Jain CD, et al. Effectiveness and Safety of Varying Doses of Linezolid With Bedaquiline and Pretomanid in Treatment of Drug-Resistant Pulmonary Tuberculosis: Open-Label, Randomized Clinical Trial. Clin Infect Dis, 2024, 79(6):1375-1385. doi:10.1093/cid/ciae388. pmid: 39194339
[50]	Li S, Tan Y, Deng Y, et al. The emerging threat of fluroqui-nolone-, bedaquiline-, and linezolid-resistant Mycobacterium tuberculosis in China: Observations on surveillance data. J Infect Public Health, 2024, 17(1):137-142. doi:10.1016/j.jiph.2023.11.018.
[51]	Azimi T, Khoshnood S, Asadi A, et al. Linezolid resistance in multidrug-resistant mycobacterium tuberculosis: A systematic review and meta-analysis. Front Pharmacol, 2022, 13:955050. doi:10.3389/fphar.2022.955050.
[52]	Chiang SS, Brooks MB, Jenkins HE, et al. Concordance of Drug-resistance Profiles Between Persons With Drug-resistant Tuberculosis and Their Household Contacts: A Systematic Review and Meta-analysis. Clin Infect Dis, 2021, 73(2):250-263. doi:10.1093/cid/ciaa613.
[53]	Corloteanu A. The resistance profile of M.tuberculosis in secondary cases of tuberculosis in relation to the index case. Bulletin of the Academy of Sciences of Moldova, Medical Sciences, 2024, 23:78-84. doi:10.52692/1857-0011.2023.3-77.12.
[54]	Seid G, Alemu A, Diriba G, et al. Drug resistance profile of Mycobacterium tuberculosis complex isolated from pulmonary tuberculosis patients and their household contacts in central Ethiopia. BMC Infect Dis, 2025, 25(1):806. doi:10.1186/s12879-025-11220-x.
[55]	单志力, 李君, 逄颖鑫, 等. 温州市耐多药/耐利福平肺结核空间聚集性分析. 预防医学, 2019, 31(3): 242-245. doi:10.19485/j.cnki.issn2096-5087.2019.03.006.