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

Abstract

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 the beta -acyl side chain. The kinetic interactions between ceftibuten and active-site serine and metallo-beta -lactamases were investigated. The activity of several TEM-derived extended spectrum beta -lactamases (ES beta Ls) against ceftibuten, cefotaxime and ceftazidime was compared using K-m, K-cat and K-cat/K-m. Ceftibuten behaved as a poor substrate for class A and B beta -lactamases compared with cefotaxime. The chromosomal class C beta -lactamase from Enterobacter cloacae 908R gave a high k(cat) value (21 s(-1)), whereas there was poor activity with enzymes from Acinetobacter baumannii and Morganella morganii and ceftibuten. Ceftibuten resists hydrolysis in the presence of typical respiratory or urogenital-tract pathogens producing beta -lactamases.