Split-drug regimens for the treatment of patients with sputum smear-positive pulmonary tuberculosis--a unique approach.
OBJECTIVE
To evaluate the efficacy of split-drug regimens for treatment of patients with sputum smear-positive pulmonary tuberculosis in south India.


METHODS
Randomized controlled clinical trial where eligible patients were randomly allocated to: (i) 2RE(3)HZ(3)(alt)/4RH(2) (split I): rifampicin plus ethambutol given on one day and isoniazid plus pyrazinamide the next day for first 2 months followed by rifampicin plus isoniazid twice weekly for 4 months, or (ii) 3RE(3)HZ(3)(alt)/3RH(2) (split II): similar to regimen 1, except duration was 3 months in each phase, or (iii) 2REHZ(3)/4RH(2) (control): rifampicin, isoniazid, ethambutol and pyrazinamide, given thrice weekly for 2 months followed by isoniazid and rifampicin twice weekly for 4 months. All patients were followed up clinically and bacteriologically every month up to 2 years and every 6 months for up to 5 years.


RESULTS
A favourable response (cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment) was observed in 91% of 407 patients in split I, 94% of 415 in split II and 89% of 418 in the control regimen. Ninety-one per cent of 370 patients in split I, 93% of 389 in split II and 90% of 370 in control regimens had quiescent disease at the end of 60 months. Gastrointestinal symptoms were more frequent under the control regimen (P = 0.01).


CONCLUSIONS
Split-drug regimens were as effective as the control regimen in terms of favourable response at the end of treatment and quiescent disease at 5 years, and caused fewer gastrointestinal side-effects.
Santha
T
T
Rehman
Fatima
F
Mitchison
D A
DA
Sarma
G Raghupathi
GR
Reetha
A M
AM
Prabhaker
R
R
D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D011718:Pyrazinamide / Q000008:administration & dosage / Q000009:adverse effects; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin