In a study in Singapore 310 patients with sputum smear-positive
pulmonary tuberculosis were allocated at random to daily
chemotherapy with
streptomycin,
isoniazid,
rifampin, and
pyrazinamide (1) for 2 months (2SHRZ), (2) for 1 month (1SHRZ), or (3) for 2 months without
streptomycin (2HRZ). This was followed for all patients by three times weekly
isoniazid and
rifampin to a total duration of 6 months. During the initial period of daily
chemotherapy the patients were also allocated at random to be given their HRZ either as a combined formulation (
Rifater), each
tablet containing 50 mg
isoniazid, 120 mg
rifampin, and 300 mg
pyrazinamide, or as three separate drugs. During the
Rifater versus separate drugs comparison the most common spontaneous complaints were of
nausea and
vomiting, reported by 8% of 155 patients receiving
Rifater and 7% of 155 separate drugs. Other adverse effects were also reported in similar proportions in the two series. Among 271 patients with
drug-susceptible strains of tubercle bacilli pretreatment there were no bacteriologic failures during
chemotherapy. During 18 months of subsequent follow-up bacteriologic relapse occurred in 3 (7%) of 46 2SHRZ, 2 (5%) of 42 1SHRZ, and 3 (8%) of 40 2HRZ patients allocated to
Rifater and in 0 of 47 2SHRZ, 1 (2%) of 46 1SHRZ, and 1 (2%) of 44 2HRZ patients allocated to separate drugs. There was no evidence of therapeutic benefit from continuing SHRZ administration beyond 1 month or from adding
streptomycin to HRZ. The relapse rates were slightly higher in the
Rifater series (p = 0.04). Further follow-up and results from other studies are therefore needed fully to assess the combined preparation.