title: Stability of FR264205 against AmpC beta-lactamase of Pseudomonas aeruginosa.
abstract: FR264205 is a novel parenteral 3'-aminopyrazolium cephalosporin. Here, we compared the stability of FR264205 against AmpC beta-lactamase of Pseudomonas aeruginosa with that of ceftazidime. The effect of ampD inactivation, which causes a moderate degree of hyperinducible AmpC expression, on the minimum inhibitory concentration (MIC) of FR264205 was eight-fold less than that on the MIC of ceftazidime. Hydrolysis efficiency (k(cat)/K(m)) towards FR264205 was substantially lower than that towards ceftazidime owing to a 20-fold-higher K(m) value. These results indicate that FR264205 is more stable against AmpC beta-lactamase than ceftazidime because of its low affinity.
authors.affiliation: Pharmacology Research Laboratories, Astellas Pharma Inc., 1-6, Kashima 2-chome, Yodogawa-ku, Osaka 532-8514, Japan. shinobu.takeda@jp.astellas.com
authors.forename: Shinobu
authors.initials: S
authors.lastname: Takeda
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishii
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hatano
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002442:Ceftazidime / Q000378:metabolism; D002511:Cephalosporins / Q000378:metabolism*; D017353:Gene Deletion; D008826:Microbial Sensitivity Tests; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002511:Cephalosporins; C519491:ceftolozane; D002442:Ceftazidime; C062460:AmpD protein, Bacteria; D009238:N-Acetylmuramoyl-L-alanine Amidase; C048795:AmpC beta-lactamases; D001618:beta-Lactamases