An update on cefepime and its future role in combination with novel β-lactamase inhibitors for MDR Enterobacterales and Pseudomonas aeruginosa.

Abstract

Cefepime, a wide-spectrum β-lactam antibiotic, has been in use for the treatment of serious bacterial infections for almost 25 years. Since its clinical development, there has been a dramatic shift in its dosing, with 2 g every 8 hours being preferred for serious infections to optimize pharmacokinetic/pharmacodynamic considerations. The advent of ESBLs has become a threat to its ongoing use, although future coadministration with β-lactamase inhibitors (BLIs) under development is an area of intense study. There are currently four new cefepime/BLI combinations in clinical development. Cefepime/zidebactam is generally active against MBL-producing Enterobacterales and Pseudomonas aeruginosa, in vitro and in animal studies, and cefepime/taniborbactam has activity against KPC and OXA-48 producers. Cefepime/enmetazobactam and cefepime/tazobactam are potential carbapenem-sparing agents with activity against ESBLs. Cefepime/enmetazobactam has completed Phase III and cefepime/taniborbactam is in Phase III clinical studies, where they are being tested against carbapenems or piperacillin/tazobactam for the treatment of complicated urinary tract infections. While these combinations are promising, their role in the treatment of MDR Gram-negative infections can only be determined with further clinical studies.

• Authors: Burcu Isler, Patrick Harris, Adam G Stewart, David L Paterson
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 76 Issue 3 Pg. 550-560 (02 11 2021) ISSN: 1460-2091 [Electronic] England
• PMID: 33332545 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Anti-Bacterial Agents
• Azabicyclo Compounds
• Borinic Acids
• Carboxylic Acids
• Cephalosporins
• Triazoles
• beta-Lactamase Inhibitors
• Cefepime
• enmetazobactam
• taniborbactam
• beta-Lactamases

Topics

• Animals
• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Azabicyclo Compounds
• Borinic Acids
• Carboxylic Acids
• Cefepime
• Cephalosporins (pharmacology)
• Microbial Sensitivity Tests
• Pseudomonas aeruginosa
• Triazoles
• beta-Lactamase Inhibitors (pharmacology)
• beta-Lactamases