title: Cefcapene inactivates chromosome-encoded class C beta-lactamases.
abstract: The stability of cefcapene and cefpodoxime, oral antibacterial cephalosporins, toward different classes of beta-lactamases was evaluated. For the class A beta-lactamases, TEM-1, SHV-1, and NMC-A, only the steady-state kinetic parameter ( k(cat)/ Km) values were calculated (3100 - 1.1 x 10(7) M(-1) x s(-1)), because these enzymes have very high Km values for cefpodoxime and cefotaxime. As for class B beta-lactamases L1, IMP-1, and CcrA, in general, similar k(cat)/ Km values were obtained. However, regarding class C beta-lactamases from Enterobacter cloacae, Escherichia coli, Pseudomonas aeruginosa, and Citrobacter freundii, we found major differences in stability between the two compounds. Cefpodoxime acted as a good substrate for the class C beta-lactamases, except for the enzyme from E. cloacae; its k(cat) and Km values were successfully calculated ( k(cat)/ Km, 1.8 x 10(5) - 1.2 x 10(7) M(-1) x s(-1)). On the other hand, cefcapene acted as a poor substrate or an inactivator for class C beta-lactamases; its k(2)/ K value was successfully calculated (8.7 x 10(5) - 7.0 x 10(6) M(-1) x s(-1)). In addition, k(3) values were determined for beta-lactamases from P. aeruginosa (2.3 x 10(-2) x s(-1)) and C. freundii (2.1 x 10(-1) x s(-1)). Even though these values could be calculated, transient inactivation as an enzyme reactivation reaction for all these enzymes was observed. These findings suggest the potential of cephem compounds as inhibitors of class C beta-lactamases.
authors.affiliation: Department of Microbiology, Yamanashi Medical University, Tamaho-cho, Yamanashi 490-3898, Japan.
authors.forename: Jimena
authors.initials: J
authors.lastname: Alba
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishii
authors.forename: Moreno
authors.initials: M
authors.lastname: Galleni
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Frère
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ito
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology*; D002876:Chromosomes, Bacterial; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics; D000097623:Cefpodoxime
chemical_list: D015296:Ceftizoxime; D002511:Cephalosporins; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases; D000097623:Cefpodoxime; C425944:cefcapene pivoxil hydrochloride