AmpC β-lactamase induction by avibactam and relebactam

Livermore, David M, Jamrozy, Dorota, Mushtaq, Shazad, Nichols, Wright W, Young, Katherine and Woodford, Neil (2017) AmpC β-lactamase induction by avibactam and relebactam. Journal of Antimicrobial Chemotherapy, 72 (12). 3342–3348. ISSN 0305-7453

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Abstract

Background: Diazabicyclooctanes, e.g. avibactam and relebactam, are a new class of β-lactamase inhibitors. Their spectrum includes AmpC enzymes, but it is important to understand whether they also induce these enzymes.  Methods: Levels of ampC mRNA were measured by RT–PCR during 4 h of exposure of Enterobacter cloacae, Citrobacter freundii and Pseudomonas aeruginosa (n = 5 strains per species) to avibactam, relebactam and cefoxitin at 0, 1, 4 and 32 mg/L. The method had low precision compared with conventional specific-activity-based induction assays, which are impracticable for inhibitors. Accordingly, induction was only considered to be significant if induction ratios >10 were found at two consecutive time intervals, with ‘strong induction’ if one or more of these ratios was >100.  Results: Cefoxitin, as expected, gave concentration-dependent induction for all strains, with strong induction for 13/15. At the other extreme, relebactam caused no significant induction for any strain. Avibactam gave strain-variable results, with strong concentration-dependent induction for 2/5 E. cloacae and 2/5 P. aeruginosa, but little or no induction for the other strains, including all the C. freundii strains.  Conclusions: Avibactam, but not relebactam, had some strain-variable ability to induce AmpC enzymes, though at concentrations (32 mg/L) above those reached in the patient.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 02 Aug 2017 05:06
Last Modified: 04 Nov 2020 00:51
URI: https://ueaeprints.uea.ac.uk/id/eprint/64318
DOI: 10.1093/jac/dkx298

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