EXPERIMENTAL CHEMOTHERAPY IN CHRONIC MYCOBACTERIUM-AVIUM-INTRACELLULARE INFECTION OF MICE

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Abstract
The effects of various chemotherapeutic regimens were investigated in ddY mice infected i.v. with a mouse-virulent strain, 31F093T, of M. avium-intracellulare [group]. Evaluation of therapeutic effects was based on serial counts of viable bacilli in the lung, spleen and kidney, and on weight and extent of gross diseases of the organs, and on histopathologic examination. Kanamycin [KM] alone was effective against the infection. The combination of ethambutol and rifampin with KM (KM-EMB-RMP) decreased counts in the lung. In another 3 drug regimen (KM, ethionamide and cycloserine [CS]), the effect was similar. Two 4 drug regimens, KM-EMB-RMP-cephalexin and KM-EMB-RMP-minocycline, and a 5 drug regimen, KM-EMB-RMP-CS-isoniazid, were also compared with the above 3 drug regimens; only the 5 drug regimen decreased counts in the lung more than the 3 drug regimens did. Even the 5 drug regimen did 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; the histopathologic findings were granuloma (3-6 wk of infection) and diffuse proliferative change beyond 9 wk 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 presence murine model should prove useful in evaluating experimental chemotherapy chemotherapy of M. avium-intracellulare infection.

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