title: Cefpodoxime proxetil, its in vitro antibacterial activity, affinity to bacterial penicillin-binding proteins, and synergy of bactericidal activity with serum complement and mouse-cultured macrophages.
abstract: Cefpodoxime proxetil (CS-807) is an orally active prodrug of an oxime-type cephem antibiotic. The MIC60 values of cefpodoxime (R-3746) the active form of CS-807, were 3.13, 6.25, 0.05, 0.38, 0.2, 0.1, 3.13, 3.13, 6.25, 6.25, 0.1 and 12.5 micrograms/ml against S. aureus, coagulase-negative staphylococci, S. pneumoniae, E. coli carrying R plasmids, P. vulgaris, P. rettgeri, C. freundii, S. marcescens, A. calcoaceticus, P. cepacia, ampicillin-resistant H. influenzae and B. fragilis, respectively. Its activity was stronger than that of cefaclor and ampicillin. R-3746 manifested little activity against P. aeruginosa, methicillin-resistant S. aureus, and Enterococcus spp. R-3746 showed stronger binding affinity than cefaclor with the PBP2 of S. aureus, PBPs 1a, 1bs, 2 and 3 of E. coli, PBPs 1b, 1c and 3 of P. rettgeri, and the PBP3 of P. aeruginosa than cefaclor. Synergy of the bactericidal effect between R-3746 and serum complement was moderate, although the cells of E. coli NIHJ-JC2 and S. aureus 209P were well engulfed and rapidly digested by mouse-cultured macrophages in the presence of greater than 1/8 MIC of R-3746. Good clinical efficacy can be expected of CS-807 provided its pharmacokinetics prove to be good.
authors.affiliation: Department of Bacteriology, School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yokota
authors.forename: E
authors.initials: E
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Arai
mesh_terms: D001419:Bacteria / Q000187:drug effects*; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D003165:Complement System Proteins / Q000276:immunology; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000276:immunology; D006602:Hexosyltransferases; D006801:Humans; D008264:Macrophages / Q000276:immunology; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011355:Prodrugs / Q000494:pharmacology*; D013210:Staphylococcus / Q000187:drug effects / Q000302:isolation & purification; D013211:Staphylococcus aureus / Q000187:drug effects / Q000276:immunology; D000097623:Cefpodoxime; D000097627:Cefpodoxime Proxetil
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D015296:Ceftizoxime; D002511:Cephalosporins; D003165:Complement System Proteins; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011355:Prodrugs; D000097623:Cefpodoxime; D000097627:Cefpodoxime Proxetil