In vitro and in vivo antibacterial activities of T-2588, a new oral cephalosporin, compared with those of other oral beta-lactam antibiotics.
T-2588, the pivaloyloxymethyl ester of T-2525, [6R, 7R]-7-[(z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetoamido] -3- [(5-methyl-2H-tetrazol-2-yl)methyl]-3-cephem-4-carboxylic acid, is a new oral cephalosporin. T-2525 had a widely expanded antibacterial spectrum against gram-negative and gram-positive bacteria. T-2525 was more active in vitro than cefaclor, cephalexin, and amoxicillin against members of the family Enterobacteriaceae and Branhamella catarrhalis. Moreover, it exhibited superior in vitro activity against Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae. T-2525 was highly stable to various beta-lactamases, which were classified as Richmond and Sykes types Ia, Ib, Ic, III, IV, and Vc. It had high affinities for the lethal (essential) penicillin-binding proteins of Escherichia coli, Clostridium perfringens, and Bacteroides fragilis. T-2588 had excellent therapeutic effect on systemic infections in mice with various species of gram-negative bacteria, including beta-lactamase-producing bacteria.
D000658:Amoxicillin / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D002433:Cefaclor / Q000494:pharmacology / Q000627:therapeutic use; D015281:Cefmenoxime / Q000031:analogs & derivatives*; D002506:Cephalexin / Q000494:pharmacology / Q000627:therapeutic use; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D006602:Hexosyltransferases; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011485:Protein Binding; D001618:beta-Lactamases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; C046817:cefteram pivoxil; D002433:Cefaclor; D000658:Amoxicillin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases; D015281:Cefmenoxime; D002506:Cephalexin