MICs and MBCs of Win 57273 against Mycobacterium avium and M. tuberculosis

A new quinolone, Win 57273 [1-cyclopropyl-7-(2,6-dimethyl-4-pyridinyl)-6-fluoro-1,4-dihydro-4-oxo-3 - quinolonecarboxylic acid], synthesized by Sterling Research Group, was tested in vitro against Mycobacterium tuberculosis and Mycobacterium avium strains. The broth-determined MICs of this agent ranged from 1.0 to 4.0 micrograms/ml for M. tuberculosis strains and from 0.25 to 8.0 micrograms/ml for M. avium strains. A distinctive feature of this agent, in comparison with ofloxacin and ciprofloxacin, is its substantially greater activity at the low pHs. For M. avium strains, the MICs of Win 57273 were 2.0 micrograms/ml or less for 54.5% of strains at pH 6.8 and 85.5% of strains at pH 5.0. Win 57273 was more active than ciprofloxacin against M. avium strains, and this difference was very substantial for all M. avium strains at pH 5.0. Taking into account that the predominant locations of these organisms in vivo are within the phagosomes and phagolysosomes of macrophages, i.e., in acidic environments at pH 5.0 or lower, the greater activity of Win 57273 at low pH makes this quinolone especially promising for M. avium infection. The bactericidal activity of Win 57273 for M. avium strains was the same as that of ciprofloxacin, with MBCs from 4.0 to 16.0 micrograms/ml.