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


METHODS
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.
Moulding
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Division of Respiratory and Critical Care Physiology and Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, USA. tmoulding@earthlink.net
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Rikleen
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Davidson
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D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000494:pharmacology; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000494:pharmacology; D023801:Directly Observed Therapy; D004338:Drug Combinations; D004363:Drug Utilization; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D015141:Los Angeles; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D012008:Recurrence; D012293:Rifampin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D012646:Self Administration; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000517:prevention & control*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004338:Drug Combinations; D007538:Isoniazid; D012293:Rifampin