The role of low dosage prothionamide with and without 4,4'-diaminio dipheimyl sulphone for use with isoniazld in the treatment of experimental mouse tuberculosis

To determine whether or not low dosage prothionamide (PTH), with or without dia- mino diphenyl sulphone (DDS), can replace PAS or thiacetazone as the companion drug to isoniazid (INH) in the treatment of tuberculosis, two experiments have been performed in mice. In experiment I the 2-month effectiveness of 25 mg/kg INH alone, INH + PTH (25 mg/kg) or INH + PTH - DDS (10 mg/kg) was investigated. Both PTH-containing regimens were equally effective in preventing the selection of INH- resistant mutants but PTH did not appear to add much to the bactericidal activity of INH. In experiment II the one year effectiveness of similar regimens supplemented by an initial month of streptomycin (SM) was investigated. Again PTH appeared very effective whereas DDS seemed ineffective. Therefore it seems that PTH is likely to be a good companion drug for INH when used in man at the dosage of 5 mg/kg, which is more or less equivalent to 25 mg/kg in the mouse.