実験的非定型抗酸菌症

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Thirty years have passed since the epoch-making report of the disease caused by atypical acid-fast bacilli presented by Pollak and Buhler in the beginning of the 1950s. During these three decades, the epidemiology, and the clinical features of the diseases caused by so called atypical mycobacteria have been elucidated by many investigators, who have been supported by a remarkable advance in the field of the classification of mycobacteria. Many problems are still unsolved, however, and the urgent problems to be solved exist in the treatment of Mycobacterium avium-M. intracellulare complex (M. intracellulare) infection, which is now the most prevalent disease among atypical mycobacterial infections in Japan. Because of lack of susceptibilities of M. intracellulare against various antimicrobial substances, in vitro and in vivo energetic investigations are still of paramount importance. In this lecture, the author intended to discuss the present status of experimental studies from the point of clinical mycobacteriology with intentional references to our recent studies. (1) In vitro studies: Many clinical investigators have suggested the benefits of using multidrug regimens in the treatment of M. intracellulare infections. Our in vitro studies demon strated the potentiations of the bacteriostatic effects against M. intracellulare in various 3- antituberculous drug regimens, and possibly in some 5-drug regimens on solid medium. However, the results were rather unpredictable, and the elucidation of the fundamental mechanisms of the drug resistance of M. intracellulare are urgently needed. In the study of different colony formers [thin-transparent colony-formers (T-formers), opaque dome-shaped colony-formers (D (O) formers), intermediate colony-formers (IM-formers), rough colony-formers (R-formers)], marked differences between D (O) formers and the other colony-formers were demonstrated. The D (O) formers tended to be far less resistant to a number of drugs than the others. Relative prevalences of these different colony-formers in an individual strain, especially in stock cultures, are diverse, and any evaluation of in vitro susceptibilities of stock cultures should have areference to colony morphology. (2) In vivo studies: The efforts of making a suitable animal model for experimental chemo therapy of M. intracellulare infection have been hampered by the lack of or low pathogenicity (virulence) to experimental animals of M. intracellulare. A few investigators have reported, however, reasonably virulent strains for mice, which has encouraged our efforts to select avirulent strain for mice. Our systematic search for a mouse (ddY) virulent strain was based on the following observations; that T-formers were more virulent for mice than the other colony-formers, that T-formers tended to be dysgonic on Ogawa medium, and that stock cultures for long periods of time should be avoided.
日本結核病学会の論文

実験的非定型抗酸菌症

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