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Temocillin revived

David M Livermore1, Paul M Tulkens

  • 1Antibiotic Resistance Monitoring and Reference Laboratory, Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, UK. david.livermore@hpa.org.uk

The Journal of Antimicrobial Chemotherapy
|December 20, 2008
PubMed

Insights

Temocillin, an older antibiotic, shows resistance to common beta-lactamases, offering a potential carbapenem-sparing option for Gram-negative infections. Its limitations include a lack of activity against Gram-positive bacteria and Pseudomonas.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Rising antimicrobial resistance in Gram-negative pathogens necessitates alternative treatment strategies.
  • Carbapenems are often reserved for severe infections due to widespread resistance.
  • Older antibiotics may offer viable solutions to combat emerging resistance patterns.

Purpose of the Study:

  • To evaluate the potential of temocillin as an alternative antibiotic for Gram-negative infections.
  • To assess temocillin's resistance profile against various beta-lactamases.
  • To determine the pharmacokinetic/pharmacodynamic (PK/PD) breakpoint for temocillin.

Main Methods:

  • Analysis of temocillin's resistance to classical and extended-spectrum beta-lactamases, including AmpC enzymes.
  • Chemical stability assessment for continuous infusion suitability.
  • Pharmacokinetic/pharmacodynamic modeling using Monte-Carlo simulations to establish a breakpoint.

Main Results:

  • Temocillin exhibits resistance to most classical and extended-spectrum beta-lactamases and AmpC enzymes.
  • Chemical stability supports continuous infusion administration.
  • A PK/PD breakpoint of 8 mg/L was suggested for a 4 g daily dosage.

Conclusions:

  • Temocillin is a viable option for Gram-negative infections where carbapenem resistance is a concern.
  • Its stability and resistance profile make it suitable for continuous infusion, potentially sparing carbapenems.
  • Limited activity against Gram-positive organisms, anaerobes, and Pseudomonas requires careful patient selection.

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