Five-year follow-up of a controlled trial of five 6-month regimens of chemotherapy for pulmonary tuberculosis. Hong Kong Chest Service/British Medical Research Council

Abstract

In a study in Hong Kong, Chinese patients with sputum-smear-positive pulmonary tuberculosis were allocated at random to five 6-month antituberculosis regimens. Four were pyrazinamide-containing regimens: 3 of these were given 3 times a week throughout, and contained isoniazid, rifampin, and pyrazinamide together with (1) streptomycin and ethambutol (HRZSE3), (2) streptomycin but no ethambutol (HRZS3), and (3) ethambutol but no streptomycin (HRZE3). The fourth contained the same drugs as Regimen 3, but was given daily throughout (HRZE7). The fifth regimen contained isoniazid, rifampin, streptomycin, and ethambutol, given 3 times a week, but no pyrazinamide (HRSE3). As previously reported, all 833 patients with drug-susceptible strains of tubercle bacilli pretreatment had a favorable bacteriologic response during chemotherapy, and bacteriologic relapse during the 2 yr (18 months after the end of chemotherapy) occurred in 9 (1.4%) of 626 patients in the pyrazinamide series (Regimens 1 to 4 combined) compared with 13 (7.8%) of 166 in the nonpyrazinamide series (Regimen 5) (p less than 0.001). The patients have been assessed at 4 and 5 yr after admission to the study. During the 5 yr, the total relapse rates for patients with drug-susceptible strains pretreatment were 3.4% for the pyrazinamide series compared with 10.3% for the nonpyrazinamide series (p less than 0.001). The results for the pyrazinamide series were also very good for the 104 assessable patients with strains resistant to isoniazid, streptomycin, or both drugs pretreatment: there was 1 failure during chemotherapy, 1 relapse during the first 2 yr and 2 subsequent relapses.