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-α-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.
Bibliographical noteFunding Information:
No funding was used for the production of this article. The laboratory work and pharmacokinetic/pharmacodynamic investigations of P. M. T. on β-lactams, including temocillin, are supported by the Belgian Programme of Interuniversity Poles of Attraction initiated by the Federal Office for Scientific Technical and Cultural Affairs (research projects IAP5/33 and IAP6/19), the Belgian Fonds de la Recherche Scientifique Médicale (grant numbers 3.4549.00 and 3.4542.02) and the Direction générale de la recherche et des technologies of the Région Wallonne (FIRST-Entreprise Programme).
Copyright 2009 Elsevier B.V., All rights reserved.
- α-methoxy penicillins