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JAC Advance Access originally published online on December 18, 2008
Journal of Antimicrobial Chemotherapy 2009 63(2):243-245; doi:10.1093/jac/dkn511
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© The Author 2008. 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

Leading articles

Temocillin revived

David M. Livermore1,* and Paul M. Tulkens2

1 Antibiotic Resistance Monitoring and Reference Laboratory, Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, UK 2 Unité de Pharmacologie Cellulaire et Moléculaire & Centre de Pharmacie Clinique, Université Catholique de Louvain, Bruxelles, Belgium

* Corresponding author. Tel: +44-20-8327-7223; Fax: +44-20-8327-6264; E-mail: david.livermore{at}hpa.org.uk

Resistance in Gram-negative pathogens is an increasing concern, with carbapenems often appearing as the only acceptable treatment option in serious infections. Reviving older compounds that have fallen into disuse may help to alleviate this burden. Temocillin (6-{alpha}-methoxy-ticarcillin) is resistant to most if not all classical and extended-spectrum β-lactamases and to AmpC enzymes. It is also chemically stable, allowing administration by continuous infusion. Pharmacokinetic/pharmacodynamic analysis, aided by Monte-Carlo simulations, suggests a breakpoint of 8 mg/L for the registered maximum dosage of 4 g daily. Temocillin's weaknesses, explaining its limited previous use, are a lack of activity against Gram-positive organisms, anaerobes and Pseudomonas. In settings where these are unlikely or are covered by other agents, temocillin may be useful, potentially ‘sparing’ carbapenems and having little apparent potential to select for Clostridium difficile.

Keywords: ESBLs , AmpC , {alpha}-methoxy penicillins


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