Mycobacterium intracellulare感染マウスに対するベンゾキサジノリファマイシン系薬剤KRM-1648の効果

治療開始時期の検討

抄録

Therapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, administered at the different periods of infection in Mycobacterium intracellulare-infectedmice was studied. Mice were infected intravenously with M. intracellulare (9.8-106 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 thetherapeutic efficacy of the drug against the infection was done on the basis of incidence anddegree of gross lung lesions, % organ weight (organ weight/body weight-100), and bacterialloads in the lungs and spleen. The lung lesions were not observed in the control and KRMtreatedmice at 4 weeks after infection (KRM treatment: day 1 to week 4). At 6 weeksafter infection (KRM treatment: week 2 to week 6), the lung lesions were observed in allcontrol mice, whereas 3 of the 5 mice given KRM-1648 did not show the lesions. At 8 weeksafter infection (KRM treatment: week 4 to week 8), the lung lesions were observed in allcontrol and KRM-1648-treated mice, but the degree of the lung lesions was much moreslight in mice given KRM-1648 than in control mice. The incidence and the degree of thelung lesions at 12 weeks after infection (KRM treatment: week 8 to week 12) was notdifferent in both groups. The % spleen weight between control mice and KRM-1648-treatedmice was found to be greatly different at 4 weeks after infection. The CFUs of organismsin the lungs and spleen were lower in mice treated with the agent than in control mice at 4 weeks after infection, but the rate of decrease became smaller with the lapse of time afterinfection. Thus, the chemotherapy started at 1 day to 2 weeks after infection with M. intracellulare was effective, but was not so in the advanced infection.