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JAC Advance Access originally published online on September 4, 2007
Journal of Antimicrobial Chemotherapy 2007 60(5):1045-1050; doi:10.1093/jac/dkm317
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Broad-spectrum ß-lactams for treating experimental peritonitis in mice due to Escherichia coli producing plasmid-encoded cephalosporinases

Sophie Vimont1,{dagger},{ddagger}, Daniel Aubert1,{dagger},§, Jean-Xavier Mazoit2, Laurent Poirel1 and Patrice Nordmann1,*

1 Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine de Paris-Sud, 94275 K.-Bicêtre, France 2 Laboratoire d'Anesthésie-Réanimation, Faculté de Médecine de Paris-Sud, 94276 K.-Bicêtre Cedex, France

Received 1 February 2007; returned 7 May 2007; revised 19 July 2007; accepted 31 July 2007

* Corresponding author. Tel: +33-1-45-21-36-32; Fax: +33-1-45-21-63-40; E-mail: nordmann.patrice{at}bct.aphp.fr

Objectives: To investigate the correlation between in vitro activity and in vivo efficacy of broad-spectrum ß-lactams for treating experimental infections due to Escherichia coli expressing two types of plasmid-mediated AmpC-type ß-lactamases, LAT-1 and FOX-1.

Methods: Susceptibility testing and time–kill curves were determined for piperacillin/tazobactam, ceftazidime, cefepime and imipenem. A mouse model of peritonitis was developed to determine 50% effective doses (ED50s) of ß-lactams against E. coli clinical strains producing recombinant plasmids pLAT-1 and pFOX-1.

Results: MIC and MBC values correlated with the ED50s for ceftazidime, cefepime and imipenem. Among the ß-lactams tested, both cefepime and imipenem were effective for treating peritonitis caused by E. coli strains harbouring pLAT-1 or pFOX-1, whereas ceftazidime was effective only against E. coli (pLAT-1). Piperacillin/tazobactam was not effective for treating infections with either of these two strains.

Conclusions: Piperacillin/tazobactam was not efficacious for treating infections due to E. coli producing plasmid-mediated AmpC-type ß-lactamases, whereas cefepime and imipenem were efficacious.

Keywords: E. coli , ß-lactamases , AmpC

{dagger} These authors contributed equally to this work.

{ddagger} Present address. Service de Bactériologie-Hygiène, Hôpital Tenon, 4 rue de la Chine, 75970 Paris Cedex 20, France.

§ Present address. Department of Microbiology Immunology, University of Western Ontario, London, Canada.


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