Use of Intermittent Rifampin and Pyrazinamide Therapy for Latent Tuberculosis Infection in a Targeted Tuberculin Testing Program
1Vanderbilt University School of Medicine and 2Tennessee Department of Health, Nashville, Tennessee
Background.
To determine the rates of hepatotoxicity and treatment completion associated with intermittent rifampin and pyrazinamide (RZ) therapy for latent tuberculosis infection, we evaluated a cohort of patients from a targeted tuberculin testing site in Tennessee.
Methods.From 4 February 2000 through 9 November 2001, a total of 423 patients with latent tuberculosis infection received directly observed preventive therapy (DOPT) with RZ given twice weekly for 2 months. Most of the patients were young, Hispanic males who had recently immigrated to the United States.
Results.During treatment, hepatotoxicity developed in 29 patients (6.9%; hereafter refered to as “case patients”), and peak alanine aminotransferase (ALT) levels that were >10 times the upper limit of normal were noted in 18 case patients. Of the case patients, 14 had asymptomatic hepatotoxicity, and 2 required hospitalization; none of the case patients died. Hepatotoxicity developed after the receipt of 12 doses in more than half of the case patients, and 4 case patients received all 16 doses. The risk of RZ‐associated hepatotoxicity was independently associated with older age (odds ratio [OR], 1.07 per year; 
). In total, 352 patients (83.2%) completed RZ therapy. The strongest predictors for noncompletion of RZ treatment were the development of a clinical symptom (OR, 9.73; 
) and older age (OR, 1.08 per year; 
).
Conclusions.Despite the use of DOPT, intermittent dosing, and vigilant monitoring throughout therapy, RZ was associated with an unacceptable risk of hepatotoxicity.
Received 20 April 2004; accepted 23 July 2004; electronically published 18 November 2004.
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(See the editorial commentary by Blumberg on pages 1772–5)
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