[Therapeutic efficacy of a benzoxazinorifamycin, KRM-1648, administered in various frequencies per week in Mycobacterium intracellulare-infected mice].
Mice were infected intravenously with M. intracellulare (5.2 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 1, 3 or 6 times per week, from 24h after infection to the end of experiment (week 8). Evaluation 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 (square root of organ (mg)/body (g) x 10), and bacterial loads in the lungs and spleen. The lung lesions were not observed in all experimental groups at 4 weeks after infection. At 8 weeks after infection, the lung lesions observed in all control and solute (2.5% gum arabic-0.2% Tween 80) control mice, whereas 3 of the 5 mice given KRM-1648, 3 times per week and all of 5 mice given KRM-1648, 6 times per week showed no lung lesions. Although lung lesions were observed in all mice given KRM-1648 only once per week, the degree of the lesions was much more milder in KRM-1648-treated mice than in solute control mice. The spleen weight of solute control mice and KRM-treated mice differed from each other 4 and 8 weeks after infection, especially in mice administered 6 times per week. The CFUs of organisms in the lungs and spleen were lower in mice treated with the agent than in mice given solute at 4 and 8 weeks after infection, in orders of administration of 6, 3 and 1 times per week.
Tomioka
H
H
Department of Microbiology and Immunology, Shimane Medical University, Izumo, Japan.
Sato
K
K
Saito
H
H
Dekio
S
S
Hidaka
T
T
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009164:Mycobacterium Infections / Q000188:drug therapy* / Q000473:pathology; D009162:Mycobacterium avium; D012294:Rifamycins / Q000008:administration & dosage / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects
D000904:Antibiotics, Antitubercular; D012294:Rifamycins; C068980:KRM 1648