Ceftibuten stability to active-site serine and metallo-beta-lactamases

Ceftibuten is an oral third-generation cephalosporin active against a wide range of bacteria and shows an improved stability to hydrolysis by several beta -lactamases because of the carboxyethilidine moiety at position 7 of t he beta -acyl side chain. The kinetic interactions between ceftibuten and a ctive-site serine and metallo-beta -lactamases were investigated. The activ ity of several TEM-derived extended spectrum beta -lactamases (ES beta Ls) against ceftibuten, cefotaxime and ceftazidime was compared using K-m, K-ca t and K-cat/K-m. Ceftibuten behaved as a poor substrate for class A and B b eta -lactamases compared with cefotaxime. The chromosomal class C beta -lac tamase from Enterobacter cloacae 908R gave a high k(cat) value (21 s(-1)), whereas there was poor activity with enzymes from Acinetobacter baumannii a nd Morganella morganii and ceftibuten. Ceftibuten resists hydrolysis in the presence of typical respiratory or urogenital-tract pathogens producing be ta -lactamases. (C) 2001 Published by Elsevier Science B.V. and Internation al Society of Chromotherapy. All rights reserved.