It Is Too Early to Discount the Contribution of Isoniazid to the Treatment of Tuberculous Meningitis

Standard treatment of tuberculosis in the United States includes multiple drugs, to prevent relapse and the development of drug resistance. Both pulmonary and extrapulmonary disease are treated with a 4-drug regimen—isoniazid, rifampin, pyrazinamide, and ethambutol—during the 2-month initiation stage, followed by 4 months of isoniazid and rifampin. Treatment outcomes in studies of isoniazid-resistant pulmonary tuberculosis are similar to those in studies of drug-susceptible disease [1, 2]. These studies included isoniazid and rifampin throughout, usually in addition to other drugs. The number of drugs in the regimen correlated with better outcomes, as did inclusion of pyrazinamide throughout. However, no controlled studies have been conducted of the treatment of isoniazid-resistant disease with a regimen that does not include isoniazid. Many experts believe that isoniazid contributes to treatment when resistance is of a low level [3]. The Tuberculosis Trials Consortium/US Public Health Service is currently evaluating outcomes in isoniazid-intolerant patients and in isoniazid-resistant pulmonary disease; in the study, patients are randomized to receive a regimen of rifampin, ethambutol, and pyrazinamide daily or thrice weekly for 6 months