Pucci M J, Boice-Sowek J, Kessler R E, Dougherty T J
Department of Microbiology, Bristol-Myers Squibb Company, Wallingford, Connecticut 06492-7660.
Antimicrob Agents Chemother. 1991 Nov;35(11):2312-7. doi: 10.1128/AAC.35.11.2312.
The relative binding affinities of the extended-spectrum cephalosporins cefepime, cefpirome, and cefaclidine for the penicillin-binding proteins (PBPs) of Escherichia coli K-12 and Pseudomonas aeruginosa SC8329 were determined. Affinities were calculated from competition experiments between these antibiotics and [3H]benzylpenicillin in isolated membrane preparations. The concentrations which reduced binding to a PBP by 50% (IC50s) were determined. For E. coli, all three antibiotics displayed good PBP 3 binding (IC50s of 0.5 microgram/ml or less), and MICs roughly correlated with these values. Cefepime had a greater than 20-fold-lower IC50 for PBP 2 of E. coli than the other antibiotics. For P. aeruginosa, all of the antibiotics bound poorly (greater than 25 micrograms/ml) to PBP 2 but showed excellent pseudomonal (less than 0.0025 microgram/ml) PBP 3 binding. No correlations were seen between IC50s and MICs for P. aeruginosa. Despite differences in PBP binding, cefepime, cefpirome, and cefaclidine all displayed similar bactericidal activity for E. coli K-12 over the initial 3 h after antibiotic addition. All three caused E. coli to form filaments at values close to the MICs. In addition, cefepime induced "bleb" formation along the filaments at concentrations greater than 10x the MIC.
测定了广谱头孢菌素头孢吡肟、头孢匹罗和头孢拉定对大肠杆菌K-12和铜绿假单胞菌SC8329青霉素结合蛋白（PBPs）的相对结合亲和力。亲和力通过这些抗生素与[3H]苄青霉素在分离的膜制剂中的竞争实验来计算。确定了使与PBP的结合降低50%的浓度（IC50）。对于大肠杆菌，这三种抗生素均显示出良好的PBP 3结合（IC50为0.5微克/毫升或更低），且最低抑菌浓度（MIC）大致与这些值相关。头孢吡肟对大肠杆菌PBP 2的IC50比其他抗生素低20倍以上。对于铜绿假单胞菌，所有抗生素与PBP 2的结合均较差（大于25微克/毫升），但显示出优异的假单胞菌PBP 3结合（小于0.0025微克/毫升）。铜绿假单胞菌的IC50与MIC之间未发现相关性。尽管PBP结合存在差异，但在添加抗生素后的最初3小时内，头孢吡肟、头孢匹罗和头孢拉定对大肠杆菌K-12均表现出相似的杀菌活性。这三种抗生素在接近MIC的值时均导致大肠杆菌形成丝状。此外，头孢吡肟在浓度大于MIC的10倍时会沿着丝状诱导“泡”的形成。
