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 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 beta-lactamases (ESbetaLs) 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.
Perilli
M
M
Department of Sciences and Biomedical Technologies, School of Medicine, University of L'Aquila, Via Vetoio, 67010, Coppito L' Aquila, Italy.
Segatore
B
B
Franceschini
N
N
Gizzi
G
G
Mancinelli
A
A
Caravelli
B
B
Setacci
D
D
del Tavio-Perez
M M
MM
Bianchi
B
B
Amicosante
G
G
D001665:Binding Sites; D002384:Catalysis; D000077722:Ceftibuten; D002511:Cephalosporins / Q000378:metabolism*; D004352:Drug Resistance, Microbial / Q000502:physiology; D004355:Drug Stability; D006868:Hydrolysis; D012694:Serine / Q000378:metabolism*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
D002511:Cephalosporins; D012694:Serine; D001618:beta-Lactamases; D000077722:Ceftibuten