Spangler S K, Jacobs M R, Appelbaum P C
Department of Pathology (Clinical Microbiology), Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
Antimicrob Agents Chemother. 1997 Jan;41(1):148-55. doi: 10.1128/AAC.41.1.148.
Agar dilution MIC methodology was used to test the activities of GV 118819X (sanfetrinem), ampicillin, amoxicillin, amoxicillin-clavulanate, cefpodoxime, loracarbef, levofloxacin, clarithromycin, ceftriaxone, imipenem, and vancomycin against 53 penicillin-susceptible, 84 penicillin-intermediate and 74 penicillin-resistant pneumococci isolated in the United States. GV 118819X was the most active oral beta-lactam, with MIC at which 50% of the isolates were inhibited (MIC50)/MIC90 values of 0.008/0.03, 0.06/0.5, and 0.5/1.0 micrograms/ml against penicillin-susceptible, -intermediate, and -resistant stains, respectively. Amoxicillin and amoxicillin in the presence of clavulanate (2:1) were the second most-active oral beta-lactams, followed by ampicillin and cefpodoxime; loracarbef was not active against penicillin-intermediate and -resistant strains. Clarithromycin was most active against penicillin-susceptible strains but was less active against intermediate and resistant stains. All pneumococcal stains were inhibited by ceftriaxone and imipenem at MICs of < or = 4.0 and < or = 1.0 micrograms/ml, respectively. The activities of levofloxacin and vancomycin were unaffected by penicillin susceptibility. Time-kill studies of three penicillin-susceptible, three penicillin-intermediate, and three penicillin-resistant pneumococci showed that all compounds, at the broth microdilution MIC, yielded 99.9% killing of all strains after 24 h. Kinetic patterns of all oral beta-lactams, ceftriaxone, and vancomycin were similar relative to the MIC, with 90% killing of all strains first observed after 12 h. However, killing by amoxicillin-clavulanate, imipenem, and levofloxacin was slightly faster and that by clarithromycin was slower than that by the above-described drugs. At 2 x the MIC, more strains were killed earlier than was the case at the MIC, but the pattern seen at the MIC prevailed. When MICs and kill kinetics were combined, sanfetrinem was the most active oral antipneumococcal agent in this study.
采用琼脂稀释法微量肉汤稀释法检测了GV 118819X（三苯甲基青霉素）、氨苄西林、阿莫西林、阿莫西林-克拉维酸、头孢泊肟、氯碳头孢、左氧氟沙星、克拉霉素、头孢曲松、亚胺培南和万古霉素对在美国分离出的53株青霉素敏感、84株青霉素中介和74株青霉素耐药肺炎球菌的活性。GV 118819X是活性最强的口服β-内酰胺类药物，对青霉素敏感、中介和耐药菌株的50%抑菌浓度（MIC50）/90%抑菌浓度（MIC90）值分别为0.008/0.03、0.06/0.5和0.5/1.0微克/毫升。阿莫西林及含克拉维酸（2:1）的阿莫西林是活性次之的口服β-内酰胺类药物，其次是氨苄西林和头孢泊肟；氯碳头孢对青霉素中介和耐药菌株无活性。克拉霉素对青霉素敏感菌株活性最强，但对中介和耐药菌株活性较弱。所有肺炎球菌菌株分别被头孢曲松和亚胺培南在≤4.0微克/毫升和≤1.0微克/毫升的MIC水平下抑制。左氧氟沙星和万古霉素的活性不受青霉素敏感性影响。对三株青霉素敏感、三株青霉素中介和三株青霉素耐药肺炎球菌进行的时间-杀菌研究表明，所有化合物在肉汤微量稀释法MIC水平下，24小时后对所有菌株的杀菌率均达到99.9%。所有口服β-内酰胺类药物、头孢曲松和万古霉素相对于MIC的动力学模式相似，在12小时后首次观察到对所有菌株的杀菌率达到90%。然而，阿莫西林-克拉维酸、亚胺培南和左氧氟沙星的杀菌速度略快，克拉霉素的杀菌速度比上述药物慢。在2倍MIC时，比在MIC时更早地杀死了更多菌株，但在MIC时观察到的模式仍然存在。当结合MIC和杀菌动力学时，三苯甲基青霉素是本研究中活性最强的口服抗肺炎球菌药物。
