A controlled trial of six months chemotherapy in pulmonary tuberculosis. First Report: results during chemotherapy. British Thoracic Association.

The results of six-month courses of chemotherapy with daily isoniazid and rifampicin, supplemented for the first two months by either streptomycin and pyrazinamide (EHRZ6 regimen), or by ethambutol and pyrazinamide (EHRZ6 regimen), in patients with culture-positive pulmonary tuberculosis have been studied. These results have been compared with those of a nine-month regimen of daily isoniazid and rifampicin supplemented by ethambutol for the first two months (EHR9 regimen). All patients in the three regimens achieved negative cultures before the end of chemotherapy but the rate of sputum conversion was significantly more rapid with the two pyrazinamide-containing regimens. Of the 287 patients on the SHRZ6 and EHRZ6 regimens who completed chemotherapy, 77% had achieved negative cultures at two months and 98% at three months, compared with 64% and 88% respectively of the 157 patients on the EHR9 regimen. Adverse drug reactions were not a serious problem. Of the 234 patients who started treatment with the SHRZ6 and EHRZ6 regimens, 14 (4%) developed hepatitis; among the 177 patients in the EHR9 group (who did not receive pyrazinamide), the incidence of hepatitis was also 4%. Thus the addition of pyrazinamide to regimens containing rifampicin and isoniazid did not increase the incidence of hepatitis. However, the incidence of adverse effect other than hepatitis was increased in the pyrazinamide-containing regimens, the most common being skin rashes. These results indicate that six-month regimens containing pyrazinamide do not produce undue toxicity and are worthy of further study. Their usefulness in routine clinical practice will not become clear until a further period of follow-up of patients in this study had established the incidence of subsequent relapse.