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Mushtaq, Shazad, Vickers, Anna, Woodford, Neil and Livermore, David M. 
ORCID: https://orcid.org/0000-0002-9856-3703
(2024)
Activity of aztreonam/avibactam and ceftazidime/avibactam against Enterobacterales with carbapenemase-independent carbapenem resistance.
International Journal of Antimicrobial Agents, 63 (3).
ISSN 0924-8579
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Abstract
Enterobacterales with carbapenemase-independent resistance to carbapenems are sometimes selected during therapy and, on rare occasions, cause outbreaks. Most have extended-spectrum or AmpC β-lactamases, together with changes to permeability or penicillin-binding proteins (PBPs). Newer β-lactam–β-lactamase inhibitor combinations may present useful options for infections due to these organisms. Accordingly, Clinical and Laboratory Standards Institute/European Committee on Antimicrobial Susceptibility Testing broth-microdilution was used to measure the minimum inhibitory concentrations (MICs) of ceftazidime/avibactam and aztreonam/avibactam for 51 carbapenemase-negative Enterobacterales with resistance or reduced susceptibility to carbapenems: genomic sequencing of the least-susceptible organisms was also undertaken. MICs of the two avibactam combinations cross-correlated closely, but with fewer MICs (2/51 vs. 10/51) exceeding 8+4 mg/L in the case of ceftazidime/avibactam. Raised MICs for Escherichia coli were associated with PBP3 inserts together with CMY-42 β-lactamase; correlates among Enterobacter cloacae complex isolates remain elusive, with AmpC and PBP3 sequences found to be species specific. In the case of Klebsiella spp., no MICs exceeding 2 mg/L were seen for either combination. It appears that these avibactam combinations have potential against Enterobacterales with carbapenemase-independent carbapenem resistance or reduced susceptibility, with ceftazidime/avibactam being more reliably active than aztreonam/avibactam.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | avibactam,cmy-42 β-lactamase,carbapenem-resistant enterobacterales,avibactam,penicillin-binding protein (pbp)3,microbiology (medical),infectious diseases,pharmacology (medical) ,/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 > Epidemiology and Public Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 10 Jan 2024 01:39 |
| Last Modified: | 04 Mar 2024 18:25 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/94140 |
| DOI: | 10.1016/j.ijantimicag.2023.107081 |
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