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

Drugs Exp Clin Res. 1988;14(8):495-500.

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.

MeSH terms

  • Bacteria / drug effects*
  • Bacterial Proteins*
  • Carrier Proteins / metabolism
  • Ceftizoxime / analogs & derivatives*
  • Ceftizoxime / metabolism
  • Ceftizoxime / pharmacology
  • Cephalosporins / metabolism
  • Cephalosporins / pharmacology*
  • Complement System Proteins / immunology
  • Drug Resistance, Microbial
  • Escherichia coli / drug effects
  • Escherichia coli / immunology
  • Hexosyltransferases*
  • Humans
  • Macrophages / immunology
  • Muramoylpentapeptide Carboxypeptidase / metabolism
  • Penicillin-Binding Proteins
  • Peptidyl Transferases*
  • Prodrugs / pharmacology*
  • Staphylococcus / drug effects
  • Staphylococcus / isolation & purification
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / immunology

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Cephalosporins
  • Penicillin-Binding Proteins
  • Prodrugs
  • cefpodoxime proxetil
  • cefpodoxime
  • Complement System Proteins
  • Ceftizoxime
  • Peptidyl Transferases
  • Hexosyltransferases
  • Muramoylpentapeptide Carboxypeptidase