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

Los Angeles County Department of Health Services.

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.

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.

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.

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