title: Antibacterial and pharmacokinetic properties of M14659, a new injectable semisynthetic cephalosporin.
abstract: In vitro and in vivo antibacterial activities and pharmacokinetics of M14659 were investigated. In vitro activity of M14659 was superior to that of ceftazidime against Staphylococcus aureus. Against Gram-negative bacteria except Pseudomonas aeruginosa, its activity was almost equal to that of ceftazidime. M14659 was more active against P. aeruginosa including multi-drug resistant strains than cefsulodin, cefoperazone or ceftazidime. Affinities of M14659 for penicillin-binding proteins (PBPs) of Escherichia coli and P. aeruginosa were 2 to 14 times higher for PBP-1A and PBP-1B than found for ceftazidime, and almost the same for PBP-3. In vivo activity of M14659 against S. aureus was superior to that of cefamandole, cefotaxime or ceftazidime. Against Gram-negative bacteria including P. aeruginosa, M14659 was 2 to 220 times more active than cefotaxime or ceftazidime. Plasma half-life of M14659 in mice was about 3 times longer than that of ceftazidime. M14659 administered intravenously to mice was mainly excreted in urine without metabolism, and its recovery rate was almost equal to that of ceftazidime.
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology*; D006602:Hexosyltransferases; D006868:Hydrolysis; D007267:Injections; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000037:antagonists & inhibitors; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; C055846:antibiotic M 14659; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase