Fixed-dose combination chemotherapy versus multiple, single-drug chemotherapy for tuberculosis

Patients in urban and rural areas in China with newly diagnosed pulmonary tuberculosis were randomized to treatment with fixed-dose tablets containing a combination of three antituberculosis drugs or treatment with the same drugs in single-drug tablets. All doses were given in a treatment room under the close supervision of a health care provider. For the first 2 months, the patients in group A (n = 102) were given fixed-dose tablets containing isoniazid 80 mg, rifampicin 120 mg, and pyrazinamide 250 mg, three to five tablets per day, depending on body weight. For the next 4 months, the treatment was changed to two tablets per day containing isoniazid 100 mg and rifampicin 150 mg, or three tablets per day containing isoniazid 150 mg and rifampicin 300 mg, again depending on body weight. The patients in group B (n = 103) were treated with three drugs, each in single-drug tablets, daily for the first 2 months as follows: isoniazid 300 mg, rifampicin 450-600 mg, and pyrazinamide 1.5 g. For the next 4 months, they were given isoniazid and rifampicin only. After 6 months, 98.0% and 98.1% of the sputum smears were negative in groups A and B, respectively; sputum cultures were negative in 99.0% of the patients in group A and in 98.1% of the patients in group B. Sensitivity tests showed no statistically significant differences in initial bacteriologic resistance between the two groups. Similarly, there were no significant differences in adverse effects or bacterial relapses. Responses to patient, physician, and pharmacist and administrator questionnaires revealed a significant preference for the fixed-dose regimen. Thus the fixed-dose combination tablet was found to be as effective and safe as single-drug tablets and more acceptable to patients and medical personnel, and thus may simplify closely supervised chemotherapy, making treatment programs more efficient.