PREVENTIVE CHEMOTHERAPY OF TUBERCULOSIS IN CORNELL MODEL MICE WITH COMBINATIONS OF RIFAMPIN, ISONIAZID, AND PYRAZINAMIDE

The efficacies of rifampin-containing preventive regimens were measure d in Cornell model mice in which an initially severe infection with My cobacterium tuberculosis K37Rv was first treated for 7 weeks with 25 m g of isoniazid and 1,000 mg of pyrazinamide per kg of body weight in t he diet and then with one of four test regimens given by daily oral ga vage for 6 weeks, These regimens were 15 mg of rifampin per kg alone ( R), rifampin plus 25 mg of isoniazid per kg (RH), rifampin plus 150 mg of pyrazinamide per kg (RZ), or rifampin plus isoniazid and pyrazinam ide (RHZ), The interval between the rifampin gavage and the gavage wit h the other drugs ranged from 10 to 45 min, so that interference with rifampin absorption did not occur, Mice were sacrificed at 11 and 20 w eeks after the termination of chemotherapy, with each killing being pr eceded by 3 weeks of high-dose dihydrocortisone treatment, Entire sple ens and lungs were cultured, The proportions of mice,vith positive spl eens at either killing time were 73% of 43 mice treated with R, 63% of 41 mice treated with RH, 65% of 43 mice treated with RZ, and 53% of 4 5 mice treated with RHZ, a just significant (P = 0.04) trend for fewer positive spleens with increasing numbers of drugs in the regimen, How ever, no trend was found in the corresponding proportions of mice with positive spleens or lungs, which were 81, 63, 65, and 71% for mice tr eated with R, RH, RZ, and RHZ, respectively, Thus, in the Cornell mode l, R alone, RH, RZ, and RHZ all had similar efficacies.