[Therapeutic efficacy of a benzoxazinorifamycin, KRM-1648, administered at the different periods of infection in Mycobacterium intracellulare--infected mice].

Therapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, administered at the different periods of infection in Mycobacterium intracellulare-infected mice was studied. Mice were infected intravenously with M. intracellulare (9.8 x 10(6) CFU/mouse) and then were given 0.4 mg of KRM-1648 emulsified in 2.5% gum arabic-0.2% Tween 80 by gavage, once daily six times per week, from day 1 to week 4, week 2 to week 6, week 4 to week 8, and week 8 to the end of experiment (week 12). Judgement of the therapeutic efficacy of the drug against the infection was done on the basis of incidence and degree of gross lung lesions, % organ weight (organ weight/body weight x 100), and bacterial loads in the lungs and spleen. The lung lesions were not observed in the control and KRM-treated mice at 4 weeks after infection (KRM treatment: day 1 to week 4). At 6 weeks after infection (KRM treatment: week 2 to week 6), the lung lesions were observed in all control mice, whereas 3 of the 5 mice given KRM-1648 did not show the lesions. At 8 weeks after infection (KRM treatment: week 4 to week 8), the lung lesions were observed in all control and KRM-1648-treated mice, but the degree of the lung lesions was much more slight in mice given KRM-1648 than in control mice. The incidence and the degree of the lung lesions at 12 weeks after infection (KRM treatment: week 8 to week 12) was not different in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)