title: Intermittent tuberculosis treatment for patients with isoniazid intolerance or drug resistance.
abstract: METHODS
  Twenty tuberculosis (TB) clinics in the United States and Canada.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of a 6-month intermittent regimen of rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB) in human immunodeficiency virus (HIV) negative patients with culture-confirmed pulmonary or extra-pulmonary tuberculosis and either isoniazid (INH) resistance or INH intolerance.
  
  
  METHODS
  Patients were enrolled in a single-arm clinical trial to receive intermittent dosing after at least 14 initial daily doses of RMP+PZA+EMB. Treatment was continued twice (BIW) or thrice weekly (TIW) per physician/patient preference for a total of 6 months, with 2 years of follow-up for relapse after treatment.
  
  
  RESULTS
  From 1999 to 2004, 98 patients were enrolled, 78 with reported INH resistance and 20 with INH intolerance. BIW dosing was used in 77 and TIW in 21. Study treatment was completed in 73 (74%). Reasons for discontinuation were hepatic adverse events (n= 12), other adverse effects (n= 3) and other reasons (n= 10). Failure (n= 1) and relapse (n= 2) occurred in 3 (3.5%, 95%CI 1.2-9.8) of 86 patients eligible for efficacy analysis, all occurring in patients with cavitary, acid-fast bacilli smear-positive pulmonary TB.
  
  
  CONCLUSIONS
  Intermittent RMP+PZA+EMB appears to be effective in HIV-negative patients, but the regimen is poorly tolerated, possibly due to the prolonged use of PZA. Alternative regimens of lower toxicity are needed.
authors.affiliation: Denver Public Health Department, Denver, Colorado, USA.
authors.forename: R
authors.initials: R
authors.lastname: Reves
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Heilig
authors.affiliation: Denver Public Health Department, Denver, Colorado, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Tapy
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: L
authors.initials: L
authors.lastname: Bozeman
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Kyle
authors.affiliation: Family Health International 360, Durham, North Carolina, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Hamilton
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bock
authors.affiliation: University of Washington, Seattle, Washington, USA.
authors.forename: M
authors.initials: M
authors.lastname: Narita
authors.affiliation: South Texas-Audie Murphy VA Hospital Research Collaboration, Harlingen, Texas, USA.
authors.forename: D
authors.initials: D
authors.lastname: Wing
authors.affiliation: University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Hershfield
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Goldberg
mesh_terms: D000328:Adult; D000554:Ambulatory Care Facilities; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002170:Canada; D023801:Directly Observed Therapy; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011718:Pyrazinamide / Q000008:administration & dosage* / Q000009:adverse effects; D012293:Rifampin / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy*; D014481:United States
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin