Sparfloxacin, ethambutol, and cortisol receptor inhibitor RU-40 555 treatment for disseminated Mycobacterium avium complex infection of normal C57BL/6 mice.
Sparfloxacin (50 mg/kg of body weight given subcutaneously each day), alone or in combination with ethambutol (50 mg/kg given subcutaneously each day), was examined for its therapeutic efficacy against experimental infection induced with the Mycobacterium avium complex in normal C57BL/6 mice. In addition, the potential anti-infective role of RU-40 555 (100 mg/kg given intraperitoneally each day), a drug that inhibits the cortisol receptors, was examined in the same model. Treatments were started 24 h after intravenous bacterial challenge and were continued for 21 days. Compared with controls, sparfloxacin or ethambutol decreased the CFU counts in spleens and lungs (P < 0.001). The sparfloxacin plus ethambutol combination was more effective than sparfloxacin alone in spleens (P < 0.001) but not in lungs. The sparfloxacin plus ethambutol plus RU-40 555 combination was more effective than the sparfloxacin plus ethambutol combination in spleens and lungs (P < 0.001). Thus, in this model, RU-40 555 enhanced the antibacterial activities of the antibiotics tested. Results of the study showed that normal C57BL/6 mice infected with the M. avium complex can be used for the evaluation of antimicrobial agents.
Perronne
C
C
Institut National de la Santé et de la Recherche Médicale, Hôpital Bichat-Claude Bernard, Paris, France.
Cohen
Y
Y
Truffot-Pernot
C
C
Grosset
J
J
Vildé
J L
JL
Pocidalo
J J
JJ
D000818:Animals; D000900:Anti-Bacterial Agents; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D004977:Ethambutol / Q000494:pharmacology*; D005240:Feasibility Studies; D005260:Female; D024841:Fluoroquinolones; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D015735:Mifepristone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009162:Mycobacterium avium / Q000187:drug effects; D015363:Quinolones / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D013154:Spleen / Q000382:microbiology; D013997:Time Factors; D014376:Tuberculosis / Q000188:drug therapy* / Q000662:veterinary*
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D005938:Glucocorticoids; D015363:Quinolones; D011965:Receptors, Glucocorticoid; C029360:hydrocortisone receptor; C075646:RU 40555; D015735:Mifepristone; D004977:Ethambutol; C061363:sparfloxacin