[Establishment of the quantitative intratracheal infection model of experimental murine mycobacteriosis].
An intratracheal infection method (IT) of experimental murine mycobacteriosis was developed for an in vivo study of antimycobacterial agents. IT-model with either of M. bovis, M. tuberculosis or M. intracellulare exhibited a much more distinct lung-specific infection than intravenous model (i.v.) with the same dose of respective mycobacterial strains. Through a series of comparative studies of benzoxazinorifamycin (KRM) with rifabutin (RBT) or rifampicin (RFP) against murine tuberculosis models, therapeutic efficacy in the lungs of IT-model was superior to those of i.v.-model with the same dose of respective drugs (Fig. 2). In IT-model of M. bovis Ravenel infection, three rifamycin derivatives gave "distinctive dose-response curves" in the correlation of dose sizes with the mean survival times or "log10 CFU/lungs reductions". Moreover, based on the results of "log10 CFU reductions" in different organs in M. tuberculosis Kurono infection models, "characteristic in vivo activity patterns of each rifamycin" was obtained. An outline of the new methods for evaluating and characterizing the in vivo activities of antimycobacterial agents was presented in Fig. 3. This IT-model may be useful not only for the in vivo assessment of antimycobacterial agents but also for the comparison of virulence among various mycobacterial strains.
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Department of Basic Research, Japan Anti-Tuberculosis Association, Tokyo.
D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D014132:Trachea; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000635:transmission*