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Antimicrobial Agents and Chemotherapy, May 2009, p. 1766-1771, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01410-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Extended-Spectrum Cephalosporinases in Pseudomonas aeruginosa{triangledown}

José-Manuel Rodríguez-Martínez, Laurent Poirel, and Patrice Nordmann*

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

Received 21 October 2008/ Returned for modification 31 December 2008/ Accepted 14 February 2009

The characterization of AmpC-type β-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 β-lactamase, and the MICs of ceftazidime and imipenem were reduced after cloxacillin addition. Cloning and sequencing identified 10 AmpC β-lactamase variants. Reduced susceptibility to imipenem, ceftazidime, and cefepime was observed only with recombinant P. aeruginosa strains expressing an AmpC β-lactamase that had an alanine residue at position 105. The catalytic efficiencies (kcat/Km) 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.

* Corresponding author. Mailing address: Service de Bactériologie-Virologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre Cedex, France. Phone: 33-1-45-21-36-32. Fax: 33-1-45-21-63-40. E-mail: nordmann.patrice{at}bct.aphp.fr

{triangledown} Published ahead of print on 2 March 2009.

Antimicrobial Agents and Chemotherapy, May 2009, p. 1766-1771, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01410-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rodriguez-Martinez, J.-M., Poirel, L., Nordmann, P. (2009). Molecular Epidemiology and Mechanisms of Carbapenem Resistance in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 53: 4783-4788 [Abstract] [Full Text]  
  • Lister, P. D., Wolter, D. J., Hanson, N. D. (2009). Antibacterial-Resistant Pseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms. Clin. Microbiol. Rev. 22: 582-610 [Abstract] [Full Text]  
  • Picao, R. C., Poirel, L., Gales, A. C., Nordmann, P. (2009). Diversity of {beta}-Lactamases Produced by Ceftazidime-Resistant Pseudomonas aeruginosa Isolates Causing Bloodstream Infections in Brazil. Antimicrob. Agents Chemother. 53: 3908-3913 [Abstract] [Full Text]  


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