A controlled trial of a 4-weekly supplement of rifampicin, pyrazinamide and streptomycin in the continuation phase of a 7-month daily chemotherapy regimen for pulmonary tuberculosis. Tanzania/British Medical Research Council Collaborative Investigation

S Afr Med J. 1996 Aug;86(8):960-5.


Objective: To evaluate a monthly 'pulse' of rifampicin plus pyrazinamide plus streptomycin in the continuation phase of a short-course antituberculosis regimen.

Design: Randomised controlled trial of two 7-month chemotherapy regimens.

Setting: Inpatient chemotherapy and outpatient follow-up in Tanzania.

Patients: Smear-positive pulmonary tuberculosis.

Intervention: All patients received streptomycin plus rifampicin plus isoniazid plus pyrazinamide daily for 6 weeks followed by isoniazid daily for 24 weeks; 50%, at random, received additional doses of rifampicin, pyrazinamide and streptomycin every 4 weeks in the continuation phase. Follow-up continued for 23 months after cessation of chemotherapy.

Main outcome measures: Bacteriological failure rate at the end of chemotherapy and relapse rate after stopping.

Results: Of the 266 patients with fully sensitive strains before treatment there was one failure in each series during chemotherapy; after stopping, 5% of the 114 who received the supplement relapsed bacteriologically compared with 10% of the 113 who did not (95% CI for the difference -0.02% to + 11.3%). The results in the 37 patients with strains resistant to isoniazid pretreatment were not as good, but similar for the two regimens.

Conclusion: This study was not large enough to demonstrate a significant reduction in the relapse rate from 10% to 5%. If such a reduction were confirmed in a larger study it would represent an important improvement in efficacy. further, in an outpatient setting, the additional monthly doses might improve attendance.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / adverse effects
  • Blacks
  • Body Weight
  • Drug Administration Schedule
  • Drug Resistance, Microbial
  • Drug Therapy, Combination
  • Female
  • Humans
  • Isoniazid / administration & dosage*
  • Isoniazid / adverse effects
  • Isonicotinic Acids / urine
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / isolation & purification
  • Pyrazinamide / administration & dosage*
  • Pyrazinamide / adverse effects
  • Recurrence
  • Rifampin / administration & dosage*
  • Rifampin / adverse effects
  • Sputum / microbiology
  • Streptomycin / administration & dosage*
  • Streptomycin / adverse effects
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / urine


  • Antitubercular Agents
  • Isonicotinic Acids
  • Pyrazinamide
  • Isoniazid
  • Rifampin
  • Streptomycin