• Robert M Jasmer, Jussi J Saukkonen, Henry M Blumberg, Charles L Daley, John Bernardo, Eric Vittinghoff, Mark D King, L Masae Kawamura, Philip C Hopewell, and Short-Course Rifampin and Pyrazinamide for Tuberculosis Infection (SCRIPT) Study Investigators.
• San Francisco General Hospital Medical Center, University of California, San Francisco, California, USA. rjasmer@itsa.ucsf.edu
• Ann. Intern. Med. 2002 Oct 15;137(8):640-7.

BackgroundRifampin 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.ObjectiveTo 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.DesignMulticenter, prospective, open-label trial.SettingThree urban public health tuberculosis clinics in the United States.Patients589 adults with latent tuberculosis infection who met U.S. criteria for treatment.InterventionPatients were assigned in alternate weeks to receive rifampin and pyrazinamide daily for 2 months (n = 307) or isoniazid daily for 6 months (n = 282).MeasurementsPrimary end points were hepatotoxicity, other adverse events, and percentage of patients who completed treatment.ResultsSixteen 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.ConclusionsA 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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