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

Ceftibuten is an oral third-generation cephalosporin active against a wide range of bacteria and shows an improved stability to hydrolysis by several ß-lactamases because of the carboxyethilidine moiety at position 7 of the ß-acyl side chain. The kinetic interactions between ceftibuten and active-site serine and metallo-ß-lactamases were investigated. The activity of several TEM-derived extended spectrum ß-lactamases (ESßLs) against ceftibuten, cefotaxime and ceftazidime was compared using Km, Kcat and Kcat/Km. Ceftibuten behaved as a poor substrate for class A and B ß-lactamases compared with cefotaxime. The chromosomal class C ß-lactamase from Enterobacter cloacae 908R gave a high Kcat 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 ß-lactamases. © 2001 Elsevier Science B.V. and International Society of chemotherapy.