A study was performed on the therapeutic efficacy of
KRM-1648 combined with LC9018 in beige mice infected with Mycobacterium intracellulare. Each mouse was intravenously infected with 3.9 x 10(6) CFU, and then given 0.2 mg of
KRM-1648 emulsified in 2.5%
gum arabic-0.2%
Tween 80 by gavage once a day, six times per week, beginning 24 h after
infection for up to eight weeks. A sc injection of 0.1 mg LC9018 in saline was given once or twice per week, beginning two weeks before
infection to the end of experiment. An evaluation of the therapeutic efficacy of these drugs against the
infection was performed on the basis of incidence and degree of gross lung lesions and bacterial loads in the lungs and spleen. Lung lesions were not observed in all experimental groups at four weeks after
infection. However, at eight weeks after
infection, although lung lesions were observed in all experimental groups, the degree of lesions was much milder in those mice receiving
KRM-1648 than in the control mice. The degree of lesions in the mice receiving LC9018 was much the same as that in the control mice. Moreover, the degree of lung lesions in mice treated with
KRM-1648 alone. The CFUs of organisms in the lungs and spleen of the mice treated with
KRM-1648 were considerably lower than those of the control mice (P < 0.05), but the CFUs in the mice treated with
KRM-1648 and LC9018 were nearly the same as those mice treated with
KRM-1648.