title: Comparison of cefepime, cefpirome, and cefaclidine binding affinities for penicillin-binding proteins in Escherichia coli K-12 and Pseudomonas aeruginosa SC8329.
abstract: 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.
authors.affiliation: Department of Microbiology, Bristol-Myers Squibb Company, Wallingford, Connecticut 06492-7660.
authors.forename: M J
authors.initials: MJ
authors.lastname: Pucci
authors.forename: J
authors.initials: J
authors.lastname: Boice-Sowek
authors.forename: R E
authors.initials: RE
authors.lastname: Kessler
authors.forename: T J
authors.initials: TJ
authors.lastname: Dougherty
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D000077723:Cefepime; D002462:Cell Membrane / Q000378:metabolism; D002511:Cephalosporins / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism*; D001618:beta-Lactamases / Q000096:biosynthesis; D000097572:Cefpirome
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D000077723:Cefepime; D002511:Cephalosporins; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D001618:beta-Lactamases; D000097572:Cefpirome; C056494:cefclidin