• 中國循證醫(yī)學(xué)中心（成都 610041）;

目的　 比較利福平吡嗪酰胺聯(lián)用方案（RZ）與異煙肼方案（H）化學(xué)預(yù)防潛在結(jié)核感染的有效性和安全性。
方法 　按HIV感染與否對納入隨機(jī)對照試驗分別進(jìn)行Meta分析，納入對象為潛在結(jié)核感染者，對照組為H方案、干預(yù)組為RZ聯(lián)用方案。合并統(tǒng)計量采用率差，規(guī)定如假設(shè)檢驗結(jié)果P gt;0.05且率差95%CI在±5%之間可認(rèn)為兩方案等效或相當(dāng)。
結(jié)果 　共納入6個RCT，其中 HIV感染，非HIV感染者各3個。無論HIV感染與否，兩組患者結(jié)核病發(fā)生率相當(dāng)： HIV感染者合并率差為 0%［95%CI（–1%，2%）， P=0.89］；非HIV感染者合并率差為0%［95%CI（–2%，1%），P=0.55］。兩組患者死亡率也相當(dāng)：HIV感染者合并率差為–1%［95%CI（–4%，2%），P=0.53］，非HIV感染者合并率差為0%［95%CI（–1%，1%）， P=1.00］。亞組分析顯示，兩組非HIV感染者中RZ方案較H方案嚴(yán)重不良反應(yīng)發(fā)生率高［RD=29%，95%CI（13%，46%），P=0.000 5；vs. RD=7%，95%CI（4%，10%），P lt;0.000 1］。
結(jié)論 　目前的有限證據(jù)表明，RZ方案和H方案化學(xué)預(yù)防結(jié)核感染的有效性和死亡率相當(dāng)；對非HIV感染者的結(jié)核病化學(xué)預(yù)防，RZ方案較H方案有增加發(fā)生嚴(yán)重不良反應(yīng)的風(fēng)險。

引用本文： 高曉鳳,王莉,劉關(guān)鍵,文進(jìn),孫鑫,謝瑜,李幼平. 利福平吡嗪酰胺聯(lián)用方案與異煙肼標(biāo)準(zhǔn)方案預(yù)防性治療潛在結(jié)核感染效果的Meta分析. 中國循證醫(yī)學(xué)雜志, 2007, 07(1): 27-36. doi: 復(fù)制

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2. 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.
3. Snider DE Jr, Caras GJ. Isoniazid-associated hepatitis death: a review of available information. Am Rev Respir Dis, 1992, 145: 494–497.
4. Tulsky JP, Pilote L, Hahn JA, et al. Adherence to isoniazid prophylaxis in the homeless: a randomized controlled trial. Arch Intern Med, 2000, 160: 697–702.
5. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med, 2000, 161(Suppl): s221–247.
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8. Update: Fatal and severe liver injuries associated with rifampin and pyrazinamide treatment for latent tuberculosis infection. Morb Mortal Wkly Rep, 2002, 51: 998–999.
9. Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection---United States, 2003. Morb Mortal Wkly Rep, 2003, 52: 735–738.
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11. Alderson P, Green S, Higgins JPT. Cochrane Reviewers’ Handbook 4.2.2 [updated March 2004]. In: The Cochrane Library, Issue 1, 2004.
12. 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.
13. The European Agency for the Evaluation of Medicinal Products. Evaluation of medicines for human use: points to consider on the choice of non-inferiority margin. Available at: http://www.emea.eu.int/pdfs/human/ewp/215899en.pdf.
14. Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analysis. BMJ, 2003, 327: 557–560.
15. Sterne JAC, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ, 2001, 323: 101–105.
16. Halsey NA, Coberly JS, Desormeaux J, et al. Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection. The Lancet, 1998, l 351: 786–792.
17. Mwinga A, Hosp M, Godfrey-Faussett P, et al. Twice weekly tuberculosis preventive therapy in HIV infection in Zambia. AIDS, 1998, 12: 2447–2457.
18. Gordin F, Chaisson RE, Matts JP, et al. Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. JAMA, 2000, 283: 1445–1450.
19. Jasmer RM, Saukkonen JJ, Blumberg HM, et al. Short-Course Rifampin and Pyrazinamide Compared with Isoniazid for Latent Tuberculosis Infection: A Multicenter Clinical Trial. Ann Intern Med, 2002, 137: 640–647.
20. Leung CC, Law WS, Chang KC, et al. Initial experience on rifampin and pyrazinamide vs isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong. Chest, 2003, 124: 2112–2118.
21. Tortajada C, Martinez-Lacasa J, Sanchez F, et al. Is the combination of pyrazinamide plus rifampicin safe for treating latent tuberculosis infection in persons not infected by the human immunodeficiency virus? Int J Tuberc Lung Dis, 2005, 9: 276–281.
22. Woldehanna S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. The Cochrane library, 2006 issue 1.
23. Anonymous. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. International Union Against Tuberculosis Committee on Prophylaxis. Bulletin of the world health organization, 1982, 60: 555–564.
24. Bock NN, Rogers T, Tapia JR, et al. Acceptability of short-course rifampin and pyrazinamide treatment of latent tuberculosis infection among jail inmates. Chest, 2001, 119: 833–837.
25. Chaisson RE, Armstrong J, Stafford J, et al. Safety and tolerability of intermittent rifampin/pyrazinamide for the treatment of latent tuberculosis infection in prisoners. JAMA, 2002, 288: 165–166.
26. Lee AM, Mennone JZ, Jones RC, et al. Risk factors for hepatotoxicity associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection: experience from three public health tuberculosis clinics. Int J Tuberc Lung Dis, 2002, 6: 995–1000.
27. McNeill L, Allen M, Estrada C, et al. Pyrazinamide and Rifampin vs Isoniazid for the Treatment of Latent Tuberculosis. Chest, 2003, 123: 102–106.
28. Stout JE, Engemann JJ, Cheng AC, et al. Safety of 2 Months of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis. Am J Respir Crit Care Med, 2003, 167: 824–827.
29. Priest DH, Vossel LF, Sherfy EA, et al. Use of intermittent rifampin and pyrazinamide therapy for latent tuberculosis infection in a targeted tuberculin testing program. Clin Infect Dis, 2004, 39:1764-1771.
30. Lobato MN, Reves RR, Jasmer RM, et al. 2RZ Study Group. Adverse events and treatment completion for latent tuberculosis in jail inmates and homeless persons. Chest, 2005, 127: 1296–1303.
31. Saukkonen J. Rifampin and pyrazinamide for latent tuberculosis infection: clinical trials and general practice. Clin Infect Dis, 2004, 39: 566–568.
32. McElroy PD, Ijaz K, Lambert LA, et al. national survey to measure rates of liver injury, hospitalization, and death associated with rifampin and pyrazinamide for latent tuberculosis infection. Clin Infect Dis, 2005, 41: 1125–1133.
33. Ijaz K, Jereb JA, Lambert LA, et al. severe or fatal liver injury in 50 patients in the united states taking rifampin and pyrazinamide for latent tuberculosis infection. Clin Infect Dis, 2006: 42: 346–355.
34. Schulz KF, Chalmers I, Grimes DA, et al. Assessing the quality of randomization from reports of controlled trials published in obstetrics and gynecology. JAMA, 1994, 272: 125–128.
35. Bucher HC, Griffith LE, Guyatt GH, et al. Isoniazid prophylaxis for tuberculosis in HIV infection:a meta-analysis of randomized controlled trials. AIDS, 1999, 13: 501–507.
  1. 1. Fountain FF, Tolley E, Chrisman CR, et al. Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic. Chest, 2005, 128: 116–123.
  2. 2. 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.
  3. 3. Snider DE Jr, Caras GJ. Isoniazid-associated hepatitis death: a review of available information. Am Rev Respir Dis, 1992, 145: 494–497.
  4. 4. Tulsky JP, Pilote L, Hahn JA, et al. Adherence to isoniazid prophylaxis in the homeless: a randomized controlled trial. Arch Intern Med, 2000, 160: 697–702.
  5. 5. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med, 2000, 161(Suppl): s221–247.
  6. 6. Fatal and severe hepatitis associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection: New York and Georgia, 2000. Morb Mortal Wkly Rep, 2001, 50: 289–291.
  7. 7. Update: Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations: United States, 2001. Morb Mortal Wkly Rep, 2001, 50: 733–735.
  8. 8. Update: Fatal and severe liver injuries associated with rifampin and pyrazinamide treatment for latent tuberculosis infection. Morb Mortal Wkly Rep, 2002, 51: 998–999.
  9. 9. Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection---United States, 2003. Morb Mortal Wkly Rep, 2003, 52: 735–738.
  10. 10. Jüni P, Altman DG, Egger M. Systematic reviews in health care: Assessing the quality of controlled clinical trials. BMJ, 2001, 323: 42–46.
  11. 11. Alderson P, Green S, Higgins JPT. Cochrane Reviewers’ Handbook 4.2.2 [updated March 2004]. In: The Cochrane Library, Issue 1, 2004.
  12. 12. 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.
  13. 13. The European Agency for the Evaluation of Medicinal Products. Evaluation of medicines for human use: points to consider on the choice of non-inferiority margin. Available at: http://www.emea.eu.int/pdfs/human/ewp/215899en.pdf.
  14. 14. Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analysis. BMJ, 2003, 327: 557–560.
  15. 15. Sterne JAC, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ, 2001, 323: 101–105.
  16. 16. Halsey NA, Coberly JS, Desormeaux J, et al. Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection. The Lancet, 1998, l 351: 786–792.
  17. 17. Mwinga A, Hosp M, Godfrey-Faussett P, et al. Twice weekly tuberculosis preventive therapy in HIV infection in Zambia. AIDS, 1998, 12: 2447–2457.
  18. 18. Gordin F, Chaisson RE, Matts JP, et al. Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. JAMA, 2000, 283: 1445–1450.
  19. 19. Jasmer RM, Saukkonen JJ, Blumberg HM, et al. Short-Course Rifampin and Pyrazinamide Compared with Isoniazid for Latent Tuberculosis Infection: A Multicenter Clinical Trial. Ann Intern Med, 2002, 137: 640–647.
  20. 20. Leung CC, Law WS, Chang KC, et al. Initial experience on rifampin and pyrazinamide vs isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong. Chest, 2003, 124: 2112–2118.
  21. 21. Tortajada C, Martinez-Lacasa J, Sanchez F, et al. Is the combination of pyrazinamide plus rifampicin safe for treating latent tuberculosis infection in persons not infected by the human immunodeficiency virus? Int J Tuberc Lung Dis, 2005, 9: 276–281.
  22. 22. Woldehanna S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. The Cochrane library, 2006 issue 1.
  23. 23. Anonymous. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. International Union Against Tuberculosis Committee on Prophylaxis. Bulletin of the world health organization, 1982, 60: 555–564.
  24. 24. Bock NN, Rogers T, Tapia JR, et al. Acceptability of short-course rifampin and pyrazinamide treatment of latent tuberculosis infection among jail inmates. Chest, 2001, 119: 833–837.
  25. 25. Chaisson RE, Armstrong J, Stafford J, et al. Safety and tolerability of intermittent rifampin/pyrazinamide for the treatment of latent tuberculosis infection in prisoners. JAMA, 2002, 288: 165–166.
  26. 26. Lee AM, Mennone JZ, Jones RC, et al. Risk factors for hepatotoxicity associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection: experience from three public health tuberculosis clinics. Int J Tuberc Lung Dis, 2002, 6: 995–1000.
  27. 27. McNeill L, Allen M, Estrada C, et al. Pyrazinamide and Rifampin vs Isoniazid for the Treatment of Latent Tuberculosis. Chest, 2003, 123: 102–106.
  28. 28. Stout JE, Engemann JJ, Cheng AC, et al. Safety of 2 Months of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis. Am J Respir Crit Care Med, 2003, 167: 824–827.
  29. 29. Priest DH, Vossel LF, Sherfy EA, et al. Use of intermittent rifampin and pyrazinamide therapy for latent tuberculosis infection in a targeted tuberculin testing program. Clin Infect Dis, 2004, 39:1764-1771.
  30. 30. Lobato MN, Reves RR, Jasmer RM, et al. 2RZ Study Group. Adverse events and treatment completion for latent tuberculosis in jail inmates and homeless persons. Chest, 2005, 127: 1296–1303.
  31. 31. Saukkonen J. Rifampin and pyrazinamide for latent tuberculosis infection: clinical trials and general practice. Clin Infect Dis, 2004, 39: 566–568.
  32. 32. McElroy PD, Ijaz K, Lambert LA, et al. national survey to measure rates of liver injury, hospitalization, and death associated with rifampin and pyrazinamide for latent tuberculosis infection. Clin Infect Dis, 2005, 41: 1125–1133.
  33. 33. Ijaz K, Jereb JA, Lambert LA, et al. severe or fatal liver injury in 50 patients in the united states taking rifampin and pyrazinamide for latent tuberculosis infection. Clin Infect Dis, 2006: 42: 346–355.
  34. 34. Schulz KF, Chalmers I, Grimes DA, et al. Assessing the quality of randomization from reports of controlled trials published in obstetrics and gynecology. JAMA, 1994, 272: 125–128.
  35. 35. Bucher HC, Griffith LE, Guyatt GH, et al. Isoniazid prophylaxis for tuberculosis in HIV infection:a meta-analysis of randomized controlled trials. AIDS, 1999, 13: 501–507.