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Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults

Dick Menzies ... 呼吸系统疾病 • 2018.08.02
• 潜伏性结核分枝杆菌感染的治疗建议更新 • 潜伏性结核的治疗 • 潜伏性结核病的自我治疗 • 头孢他啶加阿维巴坦(avibactam):TB新疗法









在利福平组3,443例患者中,在7,732人-年随访期间,4例患者出现了确诊的活动性结核病,4例患者出现了临床诊断的活动性结核病,相比之下,在异烟肼组3,416例患者中,在7,652人-年随访期间,分别有4例和5例患者出现了确诊的和临床诊断的活动性结核病。确诊的活动性结核病的率差(利福平-异烟肼)低于0.01例/100人-年(95%置信区间[CI],-0.14~0.16),确诊或临床诊断的结核病的率差低于0.01例/100人-年(95% CI,-0.23~0.22)。结核病确诊病例和结核病确诊或临床诊断病例的率差的95% CI上限低于累积发生率的预设非劣效性界值(0.75个百分点);利福平方案不优于异烟肼方案。治疗完成率的差异为15.1个百分点(95% CI,12.7~17.4)。对于所有事件和肝毒性事件,146日(利福平方案的计划治疗持续时间[4个月]的120%)内发生的3~5级不良事件的率差分别为-1.1个百分点(95% CI,-1.9~-0.4)和-1.2个百分点(95% CI,-1.7~-0.7)。



对于活动性结核病的预防,利福平4个月治疗方案不劣于异烟肼9个月治疗方案,并且前者与较高的治疗完成率和较好的安全性相关(由加拿大卫生研究院[Canadian Institutes of Health Research]、澳大利亚国家健康与医学研究委员会[Australian National Health and Medical Research Council]资助;在ClinicalTrials.gov注册号为NCT00931736)。


Dick Menzies, M.D., Menonli Adjobimey, M.D., M.P.H., Rovina Ruslami, M.D., Ph.D., Anete Trajman, M.D., Ph.D., Oumou Sow, M.D., Heejin Kim, M.D., Joseph Obeng Baah, M.D., Guy B. Marks, Ph.D., F.R.A.C.P., Richard Long, M.D., Vernon Hoeppner, M.D., Kevin Elwood, M.D., Hamdan Al-Jahdali, M.D., Martin Gninafon, M.D., Lika Apriani, M.D., Raspati C. Koesoemadinata, M.D., Afranio Kritski, M.D., Ph.D., Valeria Rolla, M.D., Ph.D., Boubacar Bah, M.D., Alioune Camara, M.D., Ph.D., Isaac Boakye, B.Sc., Victoria J. Cook, M.D., Hazel Goldberg, M.B., B.S., Chantal Valiquette, C.N.A., Karen Hornby, M.Sc., Marie-Josée Dion, B.Sc., Pei-Zhi Li, M.Sc., Philip C. Hill, M.D., M.P.H., Kevin Schwartzman, M.D., M.P.H., and Andrea Benedetti, Ph.D.
From the Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University Health Centre Research Institute (D.M., A.T., C.V., K.H., M.-J.D., P.Z.L., K.S., A.B.), and the Department of Epidemiology and Biostatistics (D.M., A.B.), McGill University, Montreal, the Faculty of Medicine and Dentistry, University of Alberta, Edmonton (R.L.), the Faculty of Medicine, University of Saskatchewan, Saskatoon (V.H.), and the BC Centre for Disease Control and the University of British Columbia, Vancouver (K.E., V.J.C.) — all in Canada; Centre National Hospitalier Universitaire de Pneumo-Phtisiologie, Cotonou, Benin (M.A., M.G.); the Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia (R.R., L.A., R.C.K.); State University of Rio de Janeiro (A.T.), Programa Academico de Tuberculose–Faculdade de Medicina, Universidade Federal do Rio de Janeiro–Rede TB (A.K.), and National Institute of Infectious Diseases Evandro Chagas (V.R.) — all in Rio de Janeiro; Service de Pneumophtisiologie, Hôpital National Ignace Deen, Université Gamal Abdel Nasser de Conakry, Conakry, Guinea (O.S., B.B., A.C.); Korean Institute of Tuberculosis, Seoul, South Korea (H.K.); Komfo Anokye Teaching Hospital, Kumasi, Ghana (J.O.B., I.B.); University of New South Wales (G.B.M.) and University of Sydney (H.G.), Sydney; Centre for International Health, University of Otago, Dunedin, New Zealand (P.C.H.); and the Department of Medicine, King Saud University, King Abdulaziz Medical City, Riyadh, Saudi Arabia (H.A.-J.). Address reprint requests to Dr. Menzies at the Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University Health Centre Research Institute, 5252 Blvd. de Maisonneuve Ouest, Office 3.58, Montreal, QC H4A 3S5, Canada, or at dick.menzies@mcgill.ca.



1. Global tuberculosis report 2015. Geneva: World Health Organization, 2015. (Publication no. WHO/HTM/TB/2015.22) (http://www.who.int/tb/publications/global_report/gtbr15_main_text.pdf).

2. Houben RM, Dodd PJ. The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med 2016;13(10):e1002152-e1002152.

3. Reid A, Grant AD, White RG, et al. Accelerating progress towards tuberculosis elimination: the need for combination treatment and prevention. Int J Tuberc Lung Dis 2015;19:5-9.

4. Uplekar M, Weil D, Lonnroth K, et al. WHO’s new end TB strategy. Lancet 2015;385:1799-1801.

5. Lönnroth K, Migliori GB, Abubakar I, et al. Towards tuberculosis elimination: an action framework for low-incidence countries. Eur Respir J 2015;45:928-952.

6. American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection: this official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999: this is a joint statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC): this statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement. Am J Respir Crit Care Med 2000;161:S221-S247.

7. Menzies D, Alvarez GG, Khan K. Treatment of latent tuberculosis infection. In: Menzies D, ed. Canadian tuberculosis standards. 7th ed. Ottawa: Public Health Agency of Canada, Canadian Thoracic Society, 2014:133-169.

8. World Health Organization. Guidelines on the management of latent tuberculosis infection. 2015 (http://www.who.int/tb/publications/latent-tuberculosis-infection/en/).

9. Comstock GW. How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults? Int J Tuberc Lung Dis 1999;3:847-850.

10. Hirsch-Moverman Y, Daftary A, Franks J, Colson PW. Adherence to treatment for latent tuberculosis infection: systematic review of studies in the US and Canada. Int J Tuberc Lung Dis 2008;12:1235-1254.

11. Kopanoff DE, Snider DE Jr, Caras GJ. Isoniazid-related hepatitis: a U.S. Public Health Service cooperative surveillance study. Am Rev Respir Dis 1978;117:991-1001.

12. Page KR, Sifakis F, Montes de Oca R, et al. Improved adherence and less toxicity with rifampin vs isoniazid for treatment of latent tuberculosis: a retrospective study. Arch Intern Med 2006;166:1863-1870.

13. Lardizabal A, Passannante M, Kojakali F, Hayden C, Reichman LB. Enhancement of treatment completion for latent tuberculosis infection with 4 months of rifampin. Chest 2006;130:1712-1717.

14. Haley CA, Stephan S, Vossel LF, Sherfy EA, Laserson KF, Kainer MA. Successful use of rifampicin for Hispanic foreign-born patients with latent tuberculosis infection. Int J Tuberc Lung Dis 2008;12:160-167.

15. Hong Kong Chest Service Tuberculosis Research Centre, Madras/British Medical Research Council. A double-blind placebo-controlled clinical trial of three antituberculosis chemoprophylaxis regimens in patients with silicosis in Hong Kong. Am Rev Respir Dis 1992;145:36-41.

16. Menzies D, Dion MJ, Rabinovitch B, Mannix S, Brassard P, Schwartzman K. Treatment completion and costs of a randomized trial of rifampin for 4 months versus isoniazid for 9 months. Am J Respir Crit Care Med 2004;170:445-449.

17. Menzies D, Long R, Trajman A, et al. Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection: a randomized trial. Ann Intern Med 2008;149:689-697.

18. Aspler A, Long R, Trajman A, et al. Impact of treatment completion, intolerance and adverse events on health system costs in a randomised trial of 4 months rifampin or 9 months isoniazid for latent TB. Thorax 2010;65:582-587.

19. International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bull World Health Organ 1982;60:555-564.

20. Comstock GW, Ferebee SH. How much isoniazid is needed for prophylaxis? Am Rev Respir Dis 1970;101:780-782.

21. Saukkonen JJ, Cohn DL, Jasmer RM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 2006;174:935-952.

22. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE), v4.0. 2009 (https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf).

23. Fox GJ, Barry SE, Britton WJ, Marks GB. Contact investigation for tuberculosis: a systematic review and meta-analysis. Eur Respir J 2013;41:140-156.

24. Ferebee SH. Controlled chemoprophylaxis trials in tuberculosis: a general review. Bibl Tuberc 1970;26:28-106.

25. Morrison J, Pai M, Hopewell PC. Tuberculosis and latent tuberculosis infection in close contacts of people with pulmonary tuberculosis in low-income and middle-income countries: a systematic review and meta-analysis. Lancet Infect Dis 2008;8:359-368.

26. SAS Institute. Estimating nonlinear combinations of model parameters (http://support.sas.com/kb/58/775.html).

27. Newcombe RG. Interval estimation for the difference between independent proportions: comparison of eleven methods. Stat Med 1998;17:873-890.

28. Rothmann M, Li N, Chen G, Chi GY, Temple R, Tsou HH. Design and analysis of non-inferiority mortality trials in oncology. Stat Med 2003;22:239-264.

29. Kaul S, Diamond GA. Good enough: a primer on the analysis and interpretation of noninferiority trials. Ann Intern Med 2006;145:62-69.

30. Villarino ME, Scott NA, Weis SE, et al. Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid. JAMA Pediatr 2015;169:247-255.

31. Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med 2011;365:2155-2166.

32. Martinson NA, Barnes GL, Moulton LH, et al. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med 2011;365:11-20.

33. Schechter M, Zajdenverg R, Falco G, et al. Weekly rifapentine/isoniazid or daily rifampin/pyrazinamide for latent tuberculosis in household contacts. Am J Respir Crit Care Med 2006;173:922-926.

34. Sterling TR, Scott NA, Miro JM, et al. Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons. AIDS 2016;30:1607-1615.

35. Cuneo WD, Snider DE Jr. Enhancing patient compliance with tuberculosis therapy. Clin Chest Med 1989;10:375-380.

36. Sumartojo E. When tuberculosis treatment fails: a social behavioral account of patient adherence. Am Rev Respir Dis 1993;147:1311-1320.

37. Churchyard GJ, Fielding K, Charalambous S, et al. Efficacy of secondary isoniazid preventive therapy among HIV-infected Southern Africans: time to change policy? AIDS 2003;17:2063-2070.

38. Chaisson RE, Clermont HC, Holt EA, et al. Six-month supervised intermittent tuberculosis therapy in Haitian patients with and without HIV infection. Am J Respir Crit Care Med 1996;154:1034-1038.

39. Ena J, Valls V. Short-course therapy with rifampin plus isoniazid, compared with standard therapy with isoniazid, for latent tuberculosis infection: a meta-analysis. Clin Infect Dis 2005;40:670-676.

40. Zenner D, Beer N, Harris RJ, Lipman MC, Stagg HR, van der Werf MJ. Treatment of latent tuberculosis infection: an updated network meta-analysis. Ann Intern Med 2017;167:248-255.

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