title: Use of intermittent rifampin and pyrazinamide therapy for latent tuberculosis infection in a targeted tuberculin testing program.
abstract: 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.
authors.affiliation: Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Priest
authors.forename: Louis F
authors.initials: LF
authors.lastname: Vossel
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Sherfy
authors.forename: Debbie P
authors.initials: DP
authors.lastname: Hoy
authors.forename: Connie A
authors.initials: CA
authors.lastname: Haley
mesh_terms: 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*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D012293:Rifampin