Activity of aztreonam/avibactam and ceftazidime/avibactam against Enterobacterales with carbapenemase-independent carbapenem resistance

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. ISSN 0924-8579

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Abstract

Enterobacterales with carbapenemase-independent resistance to carbapenems are sometimes being 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, we used CLSI/EUCAST broth-microdilution to measure MICs of ceftazidime/avibactam and aztreonam/avibactam for 51 carbapenemase/negative Enterobacterales with resistance or reduced susceptibility to carbapenems and undertook genomic sequencing of the least-susceptible organisms. MICs of the two avibactam combinations MICs cross-correlated closely, but with fewer MICs (2/51 versus 10/51) exceeding 8+4 mg/L in the case of ceftazidime/avibactam. Raised MICs for Escherichia coli were associated PBP3 inserts together with CMY-42 β-lactamase; correlates among Enterobacter cloacae complex isolates remain elusive, with AmpC and PBP3 sequences found to be sub-species specific. In the case of Klebsiella spp. no MICs exceeding 2 mg/L were seen for either combination. We conclude that these avibactam combinations have potential against Enterobacterales with carbapenemase-independent carbapenem resistance or reduced susceptibility, with ceftazidime/avibactam the more reliably active.

Item Type: Article
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
Depositing User: LivePure Connector
Date Deposited: 10 Jan 2024 01:39
Last Modified: 10 Jan 2024 01:39
URI: https://ueaeprints.uea.ac.uk/id/eprint/94140
DOI: 10.1016/j.ijantimicag.2023.107081

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