Therapeutic efficacy of a benzoxazinorifamycin, KRM-1648, in Mycobacterium intracellulare infection induced in mice

Therapeutic efficacy of KRM-1648 was studied in BALB/c mice infected with Mycobacterium intracellulare. Mice were infected intravenously with 1.0 x 10(7) CFU of the organisms/mouse and then given 0.2 mg or 0.4 mg of KRM-1648 emulsified in 2.5% gum arabic-0.2% Tween 80 by gavage, once daily, 6 days per week, from day 1 to the death of mice. The therapeutic efficacy of the drug was evaluated on the basis of survival times, incidence and degree of gross lung lesions and bacterial loads in the lungs and spleen. The lung lesions were not observed in any experimental groups at 4 weeks after the infection. At 8 weeks after the infection, the lung lesions were observed in all control mice, but 2 of 5 mice treated with 0.2 mg of KRM and 4 of 5 mice treated with 0.4 mg of KRM did not show any lung lesions, and the degree of the lesions was much milder in KRM-1648-treated mice than in the control mice. All mice of treated and untreated groups died, and median survival times were 141 days for the control mice, 216 days for mice treated with 0.2 mg of KRM-1648 and 220 days for mice treated with 0.4 mg of KRM-1648. At the death, lung lesions were observed in all mice. The CFUs of M. intracellulare in the lungs and spleen in mice treated with KRM-1648 were fewer than those in the control mice at 4 and 8 weeks after the infection.(ABSTRACT TRUNCATED AT 250 WORDS)