Treatment of pulmonary tuberculosis with short course chemotherapy in south India--5-year follow up.

A controlled clinical trial of three short-course chemotherapy regimens was undertaken in patients with newly diagnosed bacteriologically positive pulmonary tuberculosis. The patients were randomly allocated to receive one of three regimens: rifampicin, streptomycin, isoniazid and pyrazinamide daily for 2 months, followed by streptomycin, isoniazid and pyrazinamide twice weekly for 3 months (R/5) or for 5 months (R/7), or the same regimen as R/7 but without rifampicin (Z/7). A bacteriological relapse requiring retreatment occurred by 5 years in 7.1% of 126 R/5, 4.0% of 124 R/7 and 6.7% of 253 Z/7 patients with organisms initially sensitive to streptomycin and isoniazid; none of these differences is statistically significant. Of the 31 relapses, 16 occurred within 2 years of the completion of chemotherapy and the remaining 15 between 2 and 5 years. Among 65 patients with initial drug resistance to streptomycin or isoniazid or both, there were six bacteriological relapses requiring retreatment.

Lack of relationship between hepatic toxicity and acetylator phenotype in three thousand South Indian patients during treatment with isoniazid for tuberculosis.

The results are presented of a retrospective analysis of the incidence of jaundice among 3,000 patients with pulmonary tuberculosis and of the activities of serum aspartate aminotransferase among 850 according to their isoniazid acetylator phenotype. The patients had been treated with a variety of isoniazid-containing regimens in a series of controlled clinical trials in South India. The results show that rapid acetylators are no more prone to develop isoniazid-induced hepatic toxicity than are slow acetylators.

Study of adverse reactions to a once-weekly regimen of streptomycin plus a slow-release preparation of isoniazid in high dosage for six months.

A once-weekly regimen of streptomycin (1 g) plus a slow-release preparation of isoniazid (matrix isoniazid) in high dosage, namely 50 mg/kg body-weight for rapid inactivators of isoniazid and 35 mg/kg for slow inactivators, was prescribed for 6 months to 64 tuberculous patients (27 rapid, 37 slow). The regimen was tolerated by most the of the patients. However, 4 rapid and 3 slow inactivators had a modification of the regimen, mainly for giddiness. There were no cases of peripheral neuropathy. No adverse effects on haemopoiesis or hepatic or renal functions were observed in any of the patients. It is concluded that it is feasible to administer matrix isoniazid in dosages considerably higher than ordinary isoniazid, in once-weekly chemotherapy.

Two controlled studies of the efficacy of isoniazid alone in preventing relapse in patients with bacteriologically quiescent pulmonary tuberculosis at the end of one year of chemotherapy.

An earlier report showed that, in patients with bacteriologically quiescent pulmonary tuberculosis at the end of 1 year of chemotherapy, isoniazid alone in a single daily dose of 150-200 mg, given as maintenance therapy in the second year, did not markedly prevent relapse over a 4-year period of follow-up in patients who had had residual cavitation (the "open-negative" syndrome) at 1 year, but was highly effective in patients who had not. As a result of these findings, two controlled studies, reported here, were undertaken.The first study was undertaken in patients with bacteriologically quiescent disease and residual cavitation at 1 year, and investigated the value of isoniazid in a higher daily dose (400 mg) throughout the second year; this is known to be the optimum therapeutic dose when isoniazid is prescribed alone for 1 year in the initial treatment of the disease. The second study was carried out in patients with bacteriologically quiescent disease and no residual cavitation at 1 year, and sought to determine the value of a shorter duration (6 months) of chemotherapy in the second year with a daily dose of 300 mg of isoniazid. Neither of the two isoniazid regimens was highly satisfactory, although both appeared to have had some effect in preventing relapse during the 4-year period of follow-up.