IN-VITRO AND IN-VIVO ANTIMYCOBACTERIAL ACTIVITIES OF A NEW QUINOLONE,DU-6859A

A new fluoroquinolone, DU-6859a, was studied for its in vitro and in v ivo antimycobacterial activities. MIC determination by the agar diluti on method with 7H11 medium revealed that DU-6859a had MICs at which 90 % of M. kansasii (0.78 mu g/ml), M. marinum (1.56 mu g/ml), M. scroful aceum (1.56 mu g/ml), M. fortuitum (0.39 mu g/ml), M. chelonae subsp. abscessus (6.25 mu g/ml), and M. chelonae subsp. chelonae (1.56 mu g/m l) were inhibited were 4 to 32 times lower than those of ofloxacin and sparfloxacin. The MICs of DU-6859a at which 90% of M. tuberculosis (0 .2 mu g/ml) and M. avium-M. intracellulare complex (12.5 mu g/ml each) were inhibited were comparable to those of sparfloxacin but were four - to eightfold lower than those of ofloxacin. Thus, DU-6859a possessed more potent in vitro activity than sparfloxacin and ofloxacin against most mycobacterial species. DU-6859a exerted significant efficacy aga inst infections caused by M. intracellulare and M. chelonae subsp. abs cessus induced in mice when it was given at a dose of 1 mg per mouse ( ca. 50 mg/kg of body weight) in terms of reducing the frequency of occ urrence and the degree of gross pulmonary or renal lesions and bacteri al loads in the lungs, spleens, or kidneys. The efficacy of DU-6859a w as greater than that of ofloxacin and was more pronounced against M. c helonae infections than against M. intracellulare infections.