Clark Catherine, Smith Kathy, Ednie Lois, Bogdanovich Tatiana, Dewasse Bonifacio, McGhee Pamela, Appelbaum Peter C
Department of Pathology, Clinical Microbiology, Hershey Medical Center, PO Box 850, Hershey, PA 17033, USA.
Antimicrob Agents Chemother. 2008 Jan;52(1):77-84. doi: 10.1128/AAC.01229-07. Epub 2007 Oct 15.
DC-159a yielded MICs of <or=1 mug/ml against 316 strains of both quinolone-susceptible and -resistant pneumococci (resistance was defined as a levofloxacin MIC >or=4 microg/ml). Although the MICs for DC-159a against quinolone-susceptible pneumococci were a few dilutions higher than those of gemifloxacin, the MICs of these two compounds against 28 quinolone-resistant pneumococci were identical. The DC-159a MICs against quinolone-resistant strains did not appear to depend on the number or the type of mutations in the quinolone resistance-determining region. DC-159a, as well as the other quinolones tested, was bactericidal after 24 h at 2x MIC against 11 of 12 strains tested. Two of the strains were additionally tested at 1 and 2 h, and DC-159a at 4x MIC showed significant killing as early as 2 h. Multistep resistance selection studies showed that even after 50 consecutive subcultures of 10 strains in the presence of sub-MICs, DC-159a produced only two mutants with maximum MICs of 1 microg/ml.
DC - 159a对316株喹诺酮敏感和耐药肺炎球菌的最低抑菌浓度(MIC)≤1μg/ml(耐药定义为左氧氟沙星MIC≥4μg/ml)。虽然DC - 159a对喹诺酮敏感肺炎球菌的MIC比吉米沙星高几个稀释度,但这两种化合物对28株喹诺酮耐药肺炎球菌的MIC相同。DC - 159a对喹诺酮耐药菌株的MIC似乎不取决于喹诺酮耐药决定区突变的数量或类型。DC - 159a以及其他测试的喹诺酮类药物,在2倍MIC浓度下作用24小时后,对12株测试菌株中的11株具有杀菌作用。另外对其中2株菌株在1小时和2小时进行了测试,4倍MIC浓度的DC - 159a早在2小时就显示出显著的杀菌效果。多步耐药选择研究表明,即使在亚抑菌浓度下对10株菌株连续传代50次后,DC - 159a仅产生了2株最大MIC为1μg/ml的突变体。