Use of intermittent rifampin and pyrazinamide therapy for latent tuberculosis infection in a targeted tuberculin testing program.
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 referred 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; P=.01). 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; P<.001) and older age (OR, 1.08 per year; P=.001).


CONCLUSIONS
Despite the use of DOPT, intermittent dosing, and vigilant monitoring throughout therapy, RZ was associated with an unacceptable risk of hepatotoxicity.
Priest
David H
DH
Vanderbilt University School of Medicine, Nashville, TN, USA.
Vossel
Louis F
LF
Sherfy
Elizabeth A
EA
Hoy
Debbie P
DP
Haley
Connie A
CA
D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000627:therapeutic use*; D012293:Rifampin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014374:Tuberculin Test; D014376:Tuberculosis / Q000188:drug therapy*
D000995:Antitubercular Agents; D011718:Pyrazinamide; D012293:Rifampin