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

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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.

Keywords: acquired resistance; anti-tuberculosis drugs; combined preparations; directly observed therapy; fixed dose combinations; self-administered treatment

Document Type: Regular Paper

Affiliations: 1: Division of Respiratory and Critical Care Physiology and Medicine, Harbor-UCLA Medical Center, Torrance, California, USA 2: TB Control Program, Los Angeles County Department of Health Services, Los Angeles, California, USA

Publication date: June 1, 2004

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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