Experimental chemotherapy in chronic Mycobacterium avium-intracellulare infection of mice

Abstract

The effects of various chemotherapeutic regimens were investigated in ddY mice infected intravenously with a mouse-virulent strain, 31F093T, of Mycobacterium avium-intracellulare. Evaluation of therapeutic effects was based on serial counts of viable bacilli in the lung, the spleen, and the kidney, as well as on weight and extent of gross diseases of the organs, and on histopathologic examination. Kanamycin alone was effective against the infection. The combination of ethambutol and rifampin with kanamycin (KM-EMB-RMP) decreased counts in the lung. In another 3-drug regimen (kanamycin, ethionamide, and cycloserine), the effect was similar. Two 4-drug regimens, KM-EMB-RMP-CEX and KM-EMB-RMP-MINO, as well as a 5-drug regimen, KM-EMB-RMP-CS-INH, were also compared with the above 3-drug regimens, and only the 5-drug regimen decreased counts in the lung more than the 3-drug regimens did. Even the 5-drug regimen, however, could not eradicate the mycobacteria in the organs of mice, which demonstrates the inveteracy of M. avium-intracellulare infection. The control mice consistently showed grossly visible disease of the lung at 6 wk of infection, and the histopathologic findings were granuloma (3 to 6 wk of infection) and diffuse proliferative change beyond 9 weeks of infection, which was persistent and slowly progressive. The spleens and livers showed extensive granulomatous changes. The subacuteness of grossly visible lung disease with significant multiplication of bacilli in the organ of the control mice in the present murine model should prove useful in evaluating experimental chemotherapy of M. avium-intracellulare infection.