Tuberculosis chemotherapy--developments in Singapore from 1957-1982.

The last 25 years have seen many important developments in tuberculosis chemotherapy in Singapore. Beginning in the 1950s, chemotherapy consisting of streptomycin (S), isoniazid (H) and p-aminosalicylic acid (PAS) was introduced at first with 2-drug and later 3-drug combinations (i.e., SPH/PH for a total of 18 to 24 months). In the 1960s, 2 early studies showed that thiacetazone (T) could not be substituted for PAS in standard chemotherapy as it was a more toxic and less potent drug. Routine tuberculosis treatment achieved good results for patients followed up for 5 years after completing treatment. A fully supervised regimen of streptomycin and isoniazid (S2H2) given twice weekly proved to be as effective as a largely self administered regimen of PAS/INH. Ethambutol (EMB) was shown to be effective in the initial treatment of pulmonary tuberculosis when combined with isoniazid. In the 1970s, rifampicin (R) was first investigated starting with an intermittent regimen of isoniazid and rifampicin given once or twice weekly. The success of this regimen led to 2 short course studies of 6-month regimens. Rifampicin was given daily for the full duration of 6 months (2SHRZ/HR; 2SHRZ/HRZ; Z = pyrazinamide) or intermittently 3 times a week in the continuation phase (2SHRZ/H3R3; 2HRZ/H3R3; 1SHRZ/H3R3). All the 6 months regimens were highly effective.