title: In vitro and in vivo activities of SCE-2787, a new parenteral cephalosporin with a broad antibacterial spectrum.
abstract: SCE-2787, a new cephalosporin having a condensed azolium moiety in the 3 position and an aminothiadiazolyl group in the 7 beta side chain, was evaluated for its in vitro and in vivo activities in comparison with those of ceftazidime, flomoxef, cefpirome, and E1040. Against methicillin-susceptible strains of Staphylococcus aureus and Staphylococcus epidermidis, SCE-2787 was more active than ceftazidime and E1040 and was as active as flomoxef and cefpirome, with MICs for 90% of strains tested (MIC90s) being 1.56 micrograms/ml or less. SCE-2787 was also active against Pseudomonas aeruginosa, for which the MIC90 was 6.25 micrograms/ml, which was lower than that of cefpirome and comparable to that of ceftazidime. SCE-2787 was marginally active against methicillin-resistant strains of staphylococci and Enterococcus faecalis, although its MIC90s were the lowest among those of the antibiotics tested. The activities of SCE-2787 against Streptococcus species, most members of the family Enterobacteriaceae, and Haemophilus influenzae exceeded those of ceftazidime and flomoxef and were comparable to those of cefpirome. Furthermore, MIC90s of SCE-2787 were significantly lower than those of ceftazidime for ceftazidime-resistant isolates of Citrobacter freundii and Enterobacter cloacae. SCE-2787 was resistant to hydrolysis by various types of beta-lactamases, including the Bush group 1 beta-lactamases, and had low affinities for these enzymes, with Km or Ki values of greater than 100 microM. The in vitro activity of SCE-2787 was reflected in its efficacy in mouse protection tests. Thus, SCE-2787 appears to be a promising cephalosporin that should be further evaluated in clinical trials.
authors.affiliation: Research and Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwahi
authors.forename: K
authors.initials: K
authors.lastname: Okonogi
authors.forename: T
authors.initials: T
authors.lastname: Yamazaki
authors.forename: S
authors.initials: S
authors.lastname: Shiki
authors.forename: M
authors.initials: M
authors.lastname: Kondo
authors.forename: A
authors.initials: A
authors.lastname: Miyake
authors.forename: A
authors.initials: A
authors.lastname: Imada
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy; D002511:Cephalosporins / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000187:drug effects; D000097586:Cefozopran
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D001618:beta-Lactamases; D000097586:Cefozopran