title: Safety and completion rate of short-course therapy for treatment of latent tuberculosis infection.
abstract: BACKGROUND
  Nine months of isoniazid therapy is the recommended regimen for treatment of latent tuberculosis infection, but low completion rates are a serious problem. The search for shorter regimens, compared with the standard isoniazid regimen, is of vital importance. We describe our experience using short-course regimens for the treatment of latent tuberculosis infection.
  
  
  METHODS
  We conducted a nonrandomized, observational study of 459 patients in a county health department from June 2000 to January 2006. Short-course therapy was defined as pyrazinamide and rifampin taken daily or twice weekly for 2 months or rifampin taken daily for 4-6 months. Conventional therapy consisted of a 9-month regimen of isoniazid. Liver function testing was performed for both groups in accordance with clinical guidelines. Treatment completion and hepatotoxicity (according to the World Health Organization classification) were determined for the short-course and conventional therapy groups.
  
  
  RESULTS
  Treatment was completed by 241 (77.7%) of 310 patients in the short-course group and by 98 (65.8%) of 149 patients in the isoniazid group (P = .009). Moderate to severe hepatotoxicity (grades 3 and 4) occurred in 6.1% of patients receiving short-course therapy and in 2.0% of patients receiving isoniazid (P=.09). The hepatotoxicity observed in the short-course group was confined to patients receiving pyrazinamide and rifampin daily and was self limited in all cases after the medications were discontinued.
  
  
  CONCLUSIONS
  The rate of treatment completion was significantly higher with short-course regimens, compared with the isoniazid regimen. Although the overall risk of hepatotoxicity in patients receiving pyrazinamide and rifampin daily for the treatment of latent tuberculosis infection was higher, liver functions returned to normal after the medications were discontinued.
authors.affiliation: Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA. cookp@ecu.edu
authors.forename: Paul P
authors.initials: PP
authors.lastname: Cook
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Maldonado
authors.forename: Connie T
authors.initials: CT
authors.lastname: Yarnell
authors.forename: Don
authors.initials: D
authors.lastname: Holbert
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D010349:Patient Compliance; D011718:Pyrazinamide / Q000008:administration & dosage* / Q000009:adverse effects; D012293:Rifampin / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D012293:Rifampin