Activity of imipenem/relebactam against Pseudomonas aeruginosa producing ESBLs and carbapenemases

Shazad Mushtaq, Daniele Meunier, Anna Vickers, Neil Woodford, David Livermore*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Background: ESBL- A nd carbapenemase-producing Pseudomonas aeruginosa are prevalent in, for example, the Middle East, Eastern Europe and Latin America, though rarer elsewhere. Because P. aeruginosa readily mutate to become carbapenem resistant via loss of OprD, isolates producing ESBLs are often as broadly resistant as those producing carbapenemases. We hypothesized that: (i) relebactam might overcome class A carbapenemases directly in P. aeruginosa; and (ii) relebactam's inhibition of AmpC, which gives a generalized potentiation of imipenem against the species, might restore imipenem susceptibility in OprD-deficient ESBL producers. Methods: MICs were determined using CLSI agar dilution for P. aeruginosa isolates producing ESBLs, principally VEB types, and for those producing GES-5, KPC and other carbapenemases. Results: Relebactam potentiated imipenem by around 4-8-fold for most P. aeruginosa isolates producing VEB and other ESBLs; however, MICs were typically only reduced to 4-16 mg/L, thus mostly remaining above EUCAST's susceptible range and only partly overlapping CLSI's intermediate range. Strong (approx. 64-fold) potentiation was seen for isolates producing KPC carbapenemases, but only 2-fold synergy for those with GES-5. Predictably, potentiation was not seen for isolates with class B or D carbapenemase activity. Conclusions: Relebactam did potentiate imipenem against ESBL-producing P. aeruginosa, which are mostly imipenem resistant via OprD loss, but this potentiation was generally insufficient to reduce imipenem MICs to the clinical range. Imipenem resistance owing to KPC carbapenemases was reversed by relebactam in P. aeruginosa, just as for Enterobacterales.

Original languageEnglish
Pages (from-to)434-442
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume76
Issue number2
DOIs
Publication statusPublished - 1 Feb 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Fingerprint

Dive into the research topics of 'Activity of imipenem/relebactam against Pseudomonas aeruginosa producing ESBLs and carbapenemases'. Together they form a unique fingerprint.

Cite this