Abstract

PIP: Numerous clinical trials of chemotherapy for tuberculosis conducted throughout the world over the past 4 decades have established 2 basic principles of treatment: effective treatment requires the initial concomitant administration of at least 2 drugs to which the patient's organisms are susceptible; and cure of tuberculosis requires that treatment continue beyond the time of sputum conversion and amelioration of symptoms. The treatment of tuberculosis was revolutionized in the late 1960s with the introduction of rifampin. Shorter regimens of 6-9 months in duration became possible. Scores of trials of short-course chemotherapy have been conducted, and more are planned. The goals of the new treatment regimens are to achieve effective sterilization of the tuberculous lesion in the shortest time possible. A table lists drugs now in use in the US and Canada and gives the usual doses, common side effects, and important interactions among drugs. Chemotherapeutic regimens acceptable for use in the US and Canada are well-defined combinations of drugs which must be regularly administered in the recommended dosages and rhythm for a specific time period. Regimens should be highly effective, i.e., a relapse rate of less than 5%, and have a low risk of toxic effects. Regimens also should be acceptable to patients and applicable on a community-wide basis. The regimens recommended meet these criteria and are backed by well-conducted clinical trails. A 9-month regimen consisting of isoniazid and rifampin throughout, usually supplemented in the initial phase by ethambutol, streptomycin, or pyrazinamide, is a well-tolerated regimen which will cure virtually all patients with susceptible organisms. The initial daily phase may last 2-8 weeks; the continuation phase may be administered daily or twice weekly. These regimens have an overall bacteriologic relapse rate of between zero and 4%. When 4 drugs -- isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin -- are given under close during supervision during the initial 2 months of daily or "induction" therapy, followed by an additional 4 months of isoniazid and rifampin, the results have been excellent. Where primary resistance to isoniazid or streptomycin is suspected, the patient should be placed on 1 of the following 3 regimens: isoniazid, rifampin, and ethambutol; isoniazid, rifampin, pyrazinamide, and streptomycin; or isoniazid, rifampin, pyrazinamide, and ethambutol. Short-course chemotherapy for extrapulmonary tuberculosis and chemotherapy of tuberculosis in children are reviewed along with several conditions which affect therapy -- tuberculosis during pregnancy, renal and hepatic disease, cancer and other conditions associated with immunosuppression, and drug interaction.