Chemotherapy of tuberculosis

Abstract

Extensive clinical trials of short-course chemotherapy regimens have established the roles of the various antituberculous drugs, whose pharmacology is also widely researched. Each drug varies in its capacity to kill bacteria, to prevent the emergence of drug resistance and to sterilize lesions. Isoniazid is the best bactericidal drug, rifampicin and pyrazinamide have good sterilizing effects and are also bactericidal to different bacterial subpopulations. The efficacy of 6 month short-course chemotherapy has been shown in a wide range of operational trials. Dosage schedules of daily treatment throughout the course, daily initial phase then an intermittent continuation phase, and intermittent throughout are equally effective. With such 6 month regimens, with compliance properly monitored, over 90% of smear-positive patients should be converted to culture-negative at 2 months, and cure rates in excess of 95% and relapse rates of under 5% are routinely possible. Regimens shorter than 6 months give unacceptably high relapse rates for smear-positive disease. A fourth drug, ethambutol, should be added to the initial phase, in countries or ethnic minority groups with an isoniazid resistance rate above 2%. There is some evidence that 4 month regimens may be satisfactory for smear-negative pulmonary tuberculosis, with fully sensitive organisms, but relapse rates are unacceptably high with any shorter duration. Human immunodeficiency virus (HIV)-positive patients should be treated for the same duration as HIV-negative patients, but a four drug initial phase should be used because of the increased likelihood of drug resistance in such patients. Treatment should be monitored, particularly if there is liver disease. Drug compliance is the major determinant of outcome. Directly observed therapy (DOT) should be used if there are doubts about compliance before initiation of treatment, or if noncompliance is demonstrated during treatment. A two or three times weekly regimen with appropriate dosage adjustments is most suitable for this purpose. Corticosteroids in addition to antituberculous treatment may be needed in a number of situations. Chemoprophylaxis with either isoniazid for 6 months or rifampicin and isoniazid for 3 months should be used for those groups at high risk of development of tuberculosis, such as household contacts of smear- positive cases or new immigrants, and for tuberculin converters.