A controlled trial of ethionamide with isoniazid in thetreatment of pulmonary tuberculosis in Hong Kong: A report from the research committee of the british tuberculosis association and the tuberculosis treatment services in Hong Kong

Abstract

Summary An investigation was undertaken among patients in Hong Kong who had pulmonarytuberculosis and denied having had previous antituberculosis chemotherapy on first enquiry. One group of patients received ethionamide 500 mg. and isoniazid 300 mg., daily in one dose in the evening combined in sugar coated tablets (the EH group). The other group received sodium PAS 12 g. and isoniazid 300 mg. daily combined in cachets in two separate doses (the PH group). Chemotherapy was given initially in hospital for 28 weeks and thereafter was continued to 52 weeks in the patient's own home, often in conditions of gross overcrowding. Sputum smear and culture examinations were made in Hong Kong and sensitivity tests in London. There were 136 patients (67 EH and 69 PH) with cultures initially sensitive to the drugs being given who were included in the main analysis. The two groups were similar in terms of age, sex and bacteriological condition on admission to the trial; the EH group had slightly more cavitation. Expressing the percentages in terms of the total number of patients initially accepted for treatment (including all those withdrawn for any reason), the proportion with negative cultures at 28 weeks was 81% of the 67 EH patients and 87% of the 69 PH patients. The proportions at 52 weeks were 85% and 87% respectively. Drug resistance emerged in 3 EH patients who were withdrawn with cultures resistantto isoniazied, ethionamide and thiacetazone (TB1), and in 6 PH patients who, on withdrawal or at 52 weeks, had cultures resistant to isoniazid in 3 and to isoniazid and PAS in 3. Radiographic improvement by the end of the year was moderate or considerable in 80%of the EH and 86% of the PH patients. Weight gains were similar in the two groups. Fifteen patients (9 EH and 6 PH) were withdrawn from the trial. Reasons for withdrawal were treatment failure in 4 EH and 5 PH, toxic effects of drugs in 5 EH and death from hepatic cirrhosis in 1 PH patient. Both drug regimens were well tolerated. Mental disturbance in 1 patient and hepatictoxicity in 1 was attributed to ethionamide and mental disturbance in another patient was attributed to ethionamide and isoniazid. Only 1 EH patient stopped treatment because of nausea and vomiting. Pretreatment cultures were resistant to one or more drugs in 19 (13%) of 148 patients(7 were resistant to isoniazid only, 5 to isoniazid and streptomycin, 1 to isoniazid and ethionamide, and 6 to streptomycin only). Nine of these patients later admitted to previous chemotherapy. Thirteen patients with initially isoniazid-resistant cultures were analysed separately: resistance to either ethionamide or PAS emerged in 8. Eight (including 6 with resistance) were withdrawn as treatment failures. One was withdrawn because of dysuria attributed to ethionamide and isoniazid. Assessment at 52 weeks of all 149 patients who started the prescribed chemotherapy showed that 137 (92%) had sputum negative on culture, 7 still had positive cultures, 3 had negative smears but no culture results, and 2 had died of hepatic failure. Cultures of ‘anonymous’ mycobacteria were obtained during the trial on one ormore occasions from 19 (13%) of 148 patients. No evidence was found to suggest that these organisms were of clinical importance. It is concluded that ethionamide 500 mg. with isoniazid 300 mg. given in a singledaily dose was highly effective in the treatment of newly diagnosed cases of pulmonary tuberculosis with cultures sensitive to these drugs. The following medical staff participated in Hong Kong:—Sr. M. Aquinas Dr. C. Au Yeung Dr. Chan Ban Dr. H. S. Chan Dr. G. K. K. Cheng Dr. P. Choy Dr. R. Dan Dr. S. Dong Dr. R. D. Foord Miss Helen Ho Dr. S. K. Kao Dr. A. S. Moodie Dr. Nip Dr. R. Ruiz Dr. J. Titmas Dr. H. Y. Wong Dr. J. G. Wright The following staff co-operated in the bacteriological studies:— Grantham Laboratory, Hong Kong. Government Laboratory, Hong Kong. Bacteriology Department, Brompton Hospital, London. Independent radiographic assessor Dr. P. A. L. Horsfall Dr. M. H. Ma-Chen Mr. Lee King Sze Dr. R. W. Riddell Mr. F. J. Baker Mrs. M. Massey Miss M. L. Worthington Dr. A. R. Somner