Short-course rifampin and pyrazinamide compared with isoniazid for latent tuberculosis infection: A multicenter clinical trial

被引:137
作者
Jasmer, RM
Saukkonen, JJ
Blumberg, HM
Daley, CL
Bernardo, J
Vittinghoff, E
King, MD
Kawamura, LM
Hopewell, PC
机构
[1] San Francisco Gen Hosp, Med Ctr, Div Pulm & Crit Care Med, San Francisco, CA 94110 USA
[2] Univ Calif San Francisco, San Francisco, CA 94143 USA
[3] Francis J Curry Natl TB Ctr, San Francisco, CA USA
[4] Boston Univ, Sch Med, Boston, MA 02118 USA
[5] Emory Univ, Sch Med, Atlanta, GA USA
[6] Grady Mem Hosp, Atlanta, GA USA
关键词
D O I
10.7326/0003-4819-137-8-200210150-00007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: 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. Objective: 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. Design: Multicenter, prospective, open-label trial. Setting: Three urban public health tuberculosis clinics in the United States. Patients: 589 adults with latent tuberculosis infection who met U.S. criteria for treatment. Intervention: 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). Measurements: Primary end points were hepatotoxicity, other adverse events, and percentage of patients who completed treatment. Results: Sixteen of 207 (7.7%) patients assigned to rifampin and pyrazinamide developed grade 3 or 4 hepatotoxicity compared with 2 of 204 (11%) patients assigned to isoniazid (odds ratio, 8.46 (95% Cl, 1.9 to 76.51; 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. Conclusions: 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.
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页码:640 / 647
页数:8
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