title: Extended-spectrum cephalosporinases in Pseudomonas aeruginosa.
abstract: The characterization of AmpC-type beta-lactamases was performed in a collection of 32 clinical Pseudomonas aeruginosa isolates with intermediate susceptibility or resistance to imipenem and ceftazidime. Twenty-one out of those 32 isolates overexpressed AmpC beta-lactamase, and the MICs of ceftazidime and imipenem were reduced after cloxacillin addition. Cloning and sequencing identified 10 AmpC beta-lactamase variants. Reduced susceptibility to imipenem, ceftazidime, and cefepime was observed only with recombinant P. aeruginosa strains expressing an AmpC beta-lactamase that had an alanine residue at position 105. The catalytic efficiencies (k(cat)/K(m)) of the AmpC variants possessing this residue were increased against oxyiminocephalosporins and imipenem. In addition, we show here that those AmpC variants constitute a favorable background for the in vitro selection of imipenem-resistant strains. This report identified a novel resistance mechanism that may contribute to imipenem resistance in P. aeruginosa.
authors.affiliation: Service de Bactériologie-Virologie, INSERM U914 Emerging Resistance to Antibiotics, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine and Université Paris-Sud, Hôpital de Bicêtre, 94275 K.-Bicêtre, France.
authors.forename: José-Manuel
authors.initials: JM
authors.lastname: Rodríguez-Martínez
authors.forename: Laurent
authors.initials: L
authors.lastname: Poirel
authors.forename: Patrice
authors.initials: P
authors.lastname: Nordmann
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002442:Ceftazidime / Q000494:pharmacology; D002510:Cephalosporinase / Q000145:classification / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D017422:Sequence Analysis, DNA; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D047090:beta-Lactams; D015378:Imipenem; D002442:Ceftazidime; D002510:Cephalosporinase; C048795:AmpC beta-lactamases; D001618:beta-Lactamases