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Antimicrobial Agents and Chemotherapy, Mar 1996, 552-555, Vol 40, No. 3
Copyright © 1996 by the American Society for Microbiology. All rights reserved.

Preventive chemotherapy of tuberculosis in Cornell model mice with combinations of rifampin, isoniazid, and pyrazinamide

J Dhillon, JM Dickinson, K Sole and DA Mitchison
Department of Bacteriology and Infectious Diseases, Royal Postgraduate Medical School, London, United Kingdom.

The efficacies of rifampin-containing preventive regimens were measured in Cornell model mice in which an initially severe infection with Mycobacterium tuberculosis H37Rv was first treated for 7 weeks with 25 mg of isoniazid and 1,000 mg of pyrazinamide per kg of body weight in the diet and then with one of four test regimens given by daily oral gavage 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 pyrazinamide (RHZ). The interval between the rifampin gavage and the gavage with 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 weeks after the termination of chemotherapy, with each killing being preceded by 3 weeks of high-dose dihydrocortisone treatment. Entire spleens and lungs were cultured. The proportions of mice with positive spleens at either killing time were 74% of 43 mice treated with R, 63% of 41 mice treated with RH, 65% of 43 mice treated with RZ, and 53% of 45 mice treated with RHZ, a just significant (P = 0.04) trend for fewer positive spleens with increasing numbers of drugs in the regimen. However, no trend was found in the corresponding proportions of mice with positive spleens or lungs, which were 81, 63, 65, and 71% for mice treated with R, RH, RZ, and RHZ, respectively. Thus, in the Cornell model, R alone, RH, RZ, and RHZ all had similar efficacies.


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