In vitro and in vivo laboratory studies on three hydroxyiminophenylacetyl cephalosporins with particular reference to SK&F 80303, an unusually long-acting cephalosporin

J Antibiot (Tokyo). 1979 Nov;32(11):1161-7. doi: 10.7164/antibiotics.32.1161.

Abstract

Three cephalosporins with 7-(2-hydroxyiminophenylacetamido) side chains (SK&F 79433, 80000 and 80303), differing in their 3-substituents, exhibited similar broad-spectrum antibacterial activity in vitro against strains of Staphylococcus aureus, Streptococcus faecalis and various Gram-negative bacilli. All three were active in vivo (s.c., mouse) against S. aureus, Escherichia coli or Klebsiella pneumoniae, but they differed significantly in serum pharmacokinetic profiles. SK&F 80303 produced high and extremely prolonged serum levels and protected mice when administered up to 24 hours prior to challenge with beta-lactamase-producing S. aureus or K. pneumoniae. It was resistant to hydrolysis by beta-lactamases from S. aureus, and variably so to beta-lactamases from E. coli strains. SK&F 80303 was bacteriolytic to logarithmically growing S. aureus, E. coli, Proteus mirabilis, K. pneumoniae and Enterobacter cloacae (partially). SK&F 80303 illustrates further the effect of the 3-sulfoalkyltetrazole substituent on the pharmacokinetic properties of cephalosporins. Its combined biological properties make it a possible candidate for therapeutic and long-term prophylactic use.

MeSH terms

  • Animals
  • Bacteria / drug effects*
  • Bacteria / enzymology
  • Blood Proteins / metabolism
  • Cefazolin / pharmacology
  • Cephalosporinase / metabolism
  • Cephalosporins / metabolism
  • Cephalosporins / pharmacology*
  • Haplorhini
  • Kinetics
  • Male
  • Mice
  • Microbial Sensitivity Tests
  • Protein Binding
  • Rabbits
  • Time Factors

Substances

  • Blood Proteins
  • Cephalosporins
  • Cephalosporinase
  • Cefazolin