Temocillin revived.
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 beta-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.
Livermore
David M
DM
Antibiotic Resistance Monitoring and Reference Laboratory, Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, UK. david.livermore@hpa.org.uk
Tulkens
Paul M
PM
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D010406:Penicillins / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D001618:beta-Lactamases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D010406:Penicillins; C031367:temocillin; D001618:beta-Lactamases