Jasmer Robert M, Saukkonen Jussi J, Blumberg Henry M, Daley Charles L, Bernardo John, Vittinghoff Eric, King Mark D, Kawamura L Masae, Hopewell Philip C
San Francisco General Hospital Medical Center, University of California, San Francisco, California, USA.
Ann Intern Med. 2002 Oct 15;137(8):640-7. doi: 10.7326/0003-4819-137-8-200210150-00007.
Rifampin and pyrazinamide are recommended for treatment of latent tuberculosis infection in adults without HIV infection, but reports of severe hepatotoxicity have raised concerns about its safety. Clinical trials have not compared this treatment with isoniazid in adults without HIV infection.
To compare the safety and tolerance of a 2-month regimen of rifampin and pyrazinamide with that of a 6-month regimen of isoniazid for treatment of latent tuberculosis infection.
Multicenter, prospective, open-label trial.
Three urban public health tuberculosis clinics in the United States.
589 adults with latent tuberculosis infection who met U.S. criteria for treatment.
Patients were assigned in alternate weeks to receive rifampin and pyrazinamide daily for 2 months (n = 307) or isoniazid daily for 6 months (n = 282).
Primary end points were hepatotoxicity, other adverse events, and percentage of patients who completed treatment.
Sixteen of 207 (7.7%) patients assigned to rifampin and pyrazinamide developed grade 3 or 4 hepatotoxicity compared with 2 of 204 (1%) patients assigned to isoniazid (odds ratio, 8.46 [95% CI, 1.9 to 76.5]; P = 0.001). The rifampin plus pyrazinamide regimen was more likely than the isoniazid regimen to be discontinued because of hepatotoxicity (odds ratio, 5.19; P = 0.033). The overall percentage of nonhepatotoxic adverse events was 20% in the rifampin-pyrazinamide group and 16% in the isoniazid group. The proportion of patients who completed the study treatment was 61% and 57%, respectively.
A 2-month regimen of rifampin and pyrazinamide was associated with an increased risk for grade 3 or 4 hepatotoxicity compared with a 6-month regimen of isoniazid. Liver enzymes should be measured routinely during treatment to screen for liver injury and prevent progression to severe toxicity.
利福平和吡嗪酰胺被推荐用于治疗未感染艾滋病毒的成人潜伏性结核感染，但严重肝毒性的报告引发了对其安全性的担忧。临床试验尚未将这种治疗方法与未感染艾滋病毒的成人使用异烟肼的治疗方法进行比较。
比较利福平和吡嗪酰胺2个月疗程与异烟肼6个月疗程治疗潜伏性结核感染的安全性和耐受性。
多中心、前瞻性、开放标签试验。
美国的三家城市公共卫生结核病诊所。
589名符合美国治疗标准的潜伏性结核感染成人。
患者每隔一周被分配接受利福平和吡嗪酰胺每日治疗2个月（n = 307）或异烟肼每日治疗6个月（n = 282）。
主要终点是肝毒性、其他不良事件以及完成治疗的患者百分比。
分配接受利福平和吡嗪酰胺治疗的207名患者中有16名（7.7%）发生3级或4级肝毒性，而分配接受异烟肼治疗的204名患者中有2名（1%）发生（比值比，8.46 [95% CI，1.9至76.5]；P = 0.001）。利福平加吡嗪酰胺方案因肝毒性而停药的可能性比异烟肼方案更大（比值比，5.19；P = 0.033）。利福平 - 吡嗪酰胺组非肝毒性不良事件的总体百分比为20%，异烟肼组为16%。完成研究治疗的患者比例分别为61%和57%。
与异烟肼6个月疗程相比，利福平和吡嗪酰胺2个月疗程与3级或4级肝毒性风险增加相关。治疗期间应常规测量肝酶以筛查肝损伤并防止进展为严重毒性。
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