Heifets L B, Lindholm-Levy P J
National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado.
Antimicrob Agents Chemother. 1990 May;34(5):770-4. doi: 10.1128/AAC.34.5.770.
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.
一种由斯特林研究集团合成的新型喹诺酮类药物Win 57273 [1-环丙基-7-(2,6-二甲基-4-吡啶基)-6-氟-1,4-二氢-4-氧代-3-喹啉羧酸]，在体外对结核分枝杆菌和鸟分枝杆菌菌株进行了测试。该药物通过肉汤法测定的结核分枝杆菌菌株的最低抑菌浓度（MIC）范围为1.0至4.0微克/毫升，鸟分枝杆菌菌株的MIC范围为0.25至8.0微克/毫升。与氧氟沙星和环丙沙星相比，该药物的一个显著特点是在低pH值下具有更高的活性。对于鸟分枝杆菌菌株，在pH 6.8时，54.5%的菌株Win 57273的MIC为2.0微克/毫升或更低，在pH 5.0时，85.5%的菌株如此。Win 57273对鸟分枝杆菌菌株的活性比环丙沙星更高，在pH 5.0时，对于所有鸟分枝杆菌菌株，这种差异非常显著。考虑到这些微生物在体内的主要存在部位是巨噬细胞的吞噬体和吞噬溶酶体内，即处于pH 5.0或更低的酸性环境中，Win 57273在低pH值下的更高活性使得这种喹诺酮类药物对鸟分枝杆菌感染特别有前景。Win 57273对鸟分枝杆菌菌株的杀菌活性与环丙沙星相同，最低杀菌浓度（MBC）为4.0至16.0微克/毫升。
