Preventing drug-resistant tuberculosis with a fixed dose combination of isoniazid and rifampin

Int J Tuberc Lung Dis. 2004 Jun;8(6):743-8.


Setting: Los Angeles County Department of Health Services.

Objective: To determine how well a self-administered fixed dose combination of isoniazid and rifampin (CombinedHR) prevents acquired drug resistance to Mycobacterium tuberculosis despite treatment interruptions.

Design: Self-administered CombinedHR was given to approximately 75% of patients and directly observed therapy or separate drugs to 25%. Three quarters of the patients completed the prescribed treatment. We determined 1) how many patients had two drug-susceptible cultures 3 or more months apart as a measure of drug-susceptible failure or relapse, 2) how many patients whose initial culture was drug-susceptible had a subsequent drug-resistant culture as a measure of acquired drug resistance, and 3) what treatment regimen was taken by each patient who developed acquired drug resistance.

Results: Among 5337 drug-susceptible tuberculosis patients who were known or presumed to be human immunodeficiency virus (HIV) negative, 152 (2.84%) treatment failures or relapses occurred, of which 25 (0.47%) developed acquired drug resistance. Among approximately 4000 cases taking CombinedHR and primarily CombinedHR, drug resistance occurred in only eight cases (0.2%), and a total of 12 cases (0.3%) when patients with indeterminate treatment histories were added.

Conclusions: Treatment with self-administered CombinedHR results in minimal acquired drug resistance in HIV-seronegative tuberculosis cases despite modest rates of incomplete treatment.

MeSH terms

  • Antibiotics, Antitubercular / administration & dosage
  • Antibiotics, Antitubercular / pharmacology
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / pharmacology
  • Directly Observed Therapy
  • Drug Combinations
  • Drug Utilization
  • Humans
  • Isoniazid / administration & dosage*
  • Isoniazid / pharmacology
  • Isoniazid / therapeutic use
  • Los Angeles
  • Mycobacterium tuberculosis / drug effects
  • Recurrence
  • Rifampin / administration & dosage*
  • Rifampin / pharmacology
  • Rifampin / therapeutic use
  • Self Administration*
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / prevention & control*
  • Tuberculosis, Pulmonary / drug therapy*


  • Antibiotics, Antitubercular
  • Antitubercular Agents
  • Drug Combinations
  • Isoniazid
  • Rifampin