Kosowska-Shick Klaudia, Credito Kim, Pankuch Glenn A, Lin Gengrong, Bozdogan Bülent, McGhee Pamela, Dewasse Bonifacio, Choi Dong-Rack, Ryu Jei Man, Appelbaum Peter C
Department of Pathology, Hershey Medical Center, PA 17033, USA.
Antimicrob Agents Chemother. 2006 Jun;50(6):2064-71. doi: 10.1128/AAC.00153-06.
DW-224a is a new broad-spectrum quinolone with excellent antipneumococcal activity. Agar dilution MIC was used to test the activity of DW-224a compared to those of penicillin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin against 353 quinolone-susceptible pneumococci. The MICs of 29 quinolone-resistant pneumococci with defined quinolone resistance mechanisms against seven quinolones and an efflux mechanism were also tested. DW-224a was the most potent quinolone against quinolone-susceptible pneumococci (MIC(50), 0.016 microg/ml; MIC(90), 0.03 microg/ml), followed by gemifloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. beta-Lactam MICs rose with those of penicillin G, and azithromycin resistance was seen mainly in strains with raised penicillin G MICs. Against the 29 quinolone-resistant strains, DW-224a had the lowest MICs (0.06 to 1 microg/ml) compared to those of gemifloxacin, clinafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. DW-224a at 2x MIC was bactericidal after 24 h against eight of nine strains tested. Other quinolones gave similar kill kinetics relative to higher MICs. Serial passages of nine strains in the presence of sub-MIC concentrations of DW-224a, moxifloxacin, levofloxacin, ciprofloxacin, gatifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin were performed. DW-224a yielded resistant clones similar to moxifloxacin and gemifloxacin but also yielded lower MICs. Azithromycin selected resistant clones in three of the five parents tested. Amoxicillin-clavulanate and cefuroxime did not yield resistant clones after 50 days.
DW - 224a是一种新型广谱喹诺酮类药物，具有出色的抗肺炎球菌活性。采用琼脂稀释法测定最低抑菌浓度（MIC），以检测DW - 224a与青霉素、环丙沙星、左氧氟沙星、加替沙星、莫西沙星、吉米沙星、阿莫西林 - 克拉维酸、头孢呋辛和阿奇霉素对353株喹诺酮敏感肺炎球菌的活性。还检测了29株具有明确喹诺酮耐药机制及外排机制的喹诺酮耐药肺炎球菌对七种喹诺酮类药物的MIC。DW - 224a是对喹诺酮敏感肺炎球菌活性最强的喹诺酮类药物（MIC50为0.016微克/毫升；MIC90为0.03微克/毫升），其次是吉米沙星、莫西沙星、加替沙星、左氧氟沙星和环丙沙星。β - 内酰胺类药物的MIC随青霉素G的MIC升高而升高，阿奇霉素耐药主要见于青霉素G MIC升高的菌株。对于29株喹诺酮耐药菌株，与吉米沙星、克林沙星、莫西沙星、加替沙星、左氧氟沙星和环丙沙星相比，DW - 224a的MIC最低（0.06至1微克/毫升）。DW - 224a在2倍MIC浓度下，对9株受试菌株中的8株在24小时后具有杀菌作用。其他喹诺酮类药物在较高MIC浓度下具有相似的杀菌动力学。在低于MIC浓度的DW - 224a、莫西沙星、左氧氟沙星、环丙沙星、加替沙星、吉米沙星、阿莫西林 - 克拉维酸、头孢呋辛和阿奇霉素存在的情况下，对9株菌株进行连续传代。DW - 224a产生的耐药克隆与莫西沙星和吉米沙星相似，但MIC也较低。阿奇霉素在5株受试亲本菌株中的3株中筛选出耐药克隆。阿莫西林 - 克拉维酸和头孢呋辛在50天后未产生耐药克隆。
