Setting: Tuberculosis Research Centre, Chennai.
Objective: To study the emergence of drug resistance during treatment and relapse among sputum positive pulmonary tuberculosis patients treated with short-course chemotherapy regimens.
Design: Retrospective analysis of randomised clinical trials using the following regimens: 2HRZE7/6HE7, 2HRZE2/4HRE2, 2HRZE3/4HR2 and 3HRZE3/3HR2. Emergence of resistance was analysed in patients with unfavourable response/relapse based on culture and susceptibility reports.
Results: Of 1817 patients studied, 1435 (79%) had susceptible strains prior to treatment; 2% of these had an unfavourable response, 7% relapsed and 1% had emergence of resistance to isoniazid, rifampicin, or both. In 320 patients with initial isoniazid resistance, 19% had an unfavourable response and 13% relapsed, while resistance to rifampicin emerged in 11%. Treatment outcomes were similar whether patients received three or two drugs in the continuation phase. Data on resistance to ethambutol and pyrazinamide were not available.
Conclusion: In this study, the overall emergence of resistance to rifampicin occurred in only 2% of patients, despite the high level (18%) of initial resistance to isoniazid. Thus, standardised short-course treatment carries only a minimal risk of emergence of rifampicin resistance.