Abstract
We evaluated the in vivo therapeutic activities of benzoxazinorifamycin KRM-1648, clarithromycin (CAM) and levofloxacin (LVFX) against Mycobacterium avium infectioninduced in mice. Mice infected intravenously with M. avium (1.4×107) were given KRM-1648 (20mg/kg), CAM (10mg/kg), or LVFX (5 mg/kg) alone, or combination of KRM-1648 with diclofenac sodium (1.25mg/kg) by gavage, once daily, five times per week, from day 1 for up to 8 weeks. The bacterial loads in the lungs and spleens were determinedby counting colony forming units of the organisms in the tissue homogenates of the visceral organs using 7H11 agar plates. Both KRM-1648 and CAM caused significantlevels of bacteriological response in mice treated with these drugs, while LVFX exertedno appreciable therapeutic effect. The therapeutic efficacies of test antimicrobials were intheorder, KRM-1648>CAM>>LVFX. The combined use of diclofenac sodium with KRM-1648 did not affect the expression of therapeutic activity of KRM-1648. This excludes thepossibility that cyclooxygenase-dependent inflammatory reactions may beinvolved in theestablishment of persistent bacterial growth of M. avium organisms at the sites of infectionin mice. Furthermore, the present study showed that the parameters of in vitroantimicrobial activities of drugs such as MIC and MBC values are not useful in predictingtheir therapeutic outcome in M. avium-infected mice.
