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Mushtaq, Shazad, Garello, Paolo, Vickers, Anna, Woodford, Neil and Livermore, David M. 
ORCID: https://orcid.org/0000-0002-9856-3703
(2021)
Cefepime/tazobactam compared with other tazobactam combinations against problem Gram-negative bacteria.
International Journal of Antimicrobial Agents, 57 (5).
ISSN 0924-8579
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Abstract
Objectives: Piperacillin/tazobactam has long been a broad-spectrum ‘workhorse’ antibiotic; however, it is compromised by resistance. One response is to re-partner tazobactam with cefepime, which is easier to protect, being less β-lactamase labile, and to use a high-dose and prolonged infusion. On this basis, Wockhardt are developing cefepime/tazobactam (WCK 4282) as a 2+2 g q8h combination with a 90-min infusion. Methods: The activity of cc cefepime/tazobactam was assessed, with other tazobactam combinations as comparators, against 1632 Enterobacterales, 745 Pseudomonas aeruginosa and 450 other non-fermenters, as submitted to the UK National Reference Laboratory. These were categorised by carbapenemase-gene detection and interpretive reading of phenotypes, with MICs determined by British Society for Antimicrobial Chemotherapy agar dilution. Results: Although higher breakpoints may be justifiable, based on the pharmacodynamics, the results were reviewed against current cefepime criteria. On this basis, cefepime/tazobactam was broadly active against Enterobacterales with AmpC enzymes and extended-spectrum β-lactamases (ESBLs), even when they had ertapenem resistance, suggesting porin loss. At 8+8 mg/L, activity extended to > 90% of Enterobacterales with OXA-48 and KPC carbapenemases, although the MICs for KPC producers belonging to the international Klebsiella pneumoniae ST258 lineage were higher; metallo-β-lactamase producers remained resistant. Cefepime/tazobactam was less active than ceftolozane/tazobactam against Pseudomonas aeruginosa with AmpC de-repression or high-level efflux but achieved wider antipseudomonal coverage than piperacillin/tazobactam. Activity against other non-fermenters was species-specific. Conclusion: Overall, cefepime/tazobactam had a spectrum exceeding those of piperacillin/tazobactam and ceftolozane/tazobactam and resembling or exceeding that of carbapenems. Used as a ‘new-combination of old-agents’ it has genuine potential to be ‘carbapenem-sparing’.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | beta-lactamase inhibitors,beta-lactamases,tazobactam,tazobactam,tazobactam,microbiology (medical),infectious diseases,pharmacology (medical),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2726 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023) Faculty of Medicine and Health Sciences > Research Groups > Epidemiology and Public Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 09 Mar 2021 00:42 |
| Last Modified: | 23 Oct 2022 02:17 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/79406 |
| DOI: | 10.1016/j.ijantimicag.2021.106318 |
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