In vitro and in vivo laboratory studies on three hydroxyiminophenylacetyl cephalosporins with particular reference to SK&F 80303, an unusually long-acting cephalosporin.
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.
D000818:Animals; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology; D001798:Blood Proteins / Q000378:metabolism; D002437:Cefazolin / Q000494:pharmacology; D002510:Cephalosporinase / Q000378:metabolism; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D000882:Haplorhini; D007700:Kinetics; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D011485:Protein Binding; D011817:Rabbits; D013997:Time Factors
D001798:Blood Proteins; D002511:Cephalosporins; D002510:Cephalosporinase; D002437:Cefazolin