Potentiation of #imipenem by #relebactam for #Pseudomonas aeruginosa from #bacteraemia and respiratory infections (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Potentiation of imipenem by relebactam for Pseudomonas aeruginosa from bacteraemia and respiratory infections

Carolyne Horner, Shazad Mushtaq, David M Livermore, BSAC Resistance Surveillance Standing Committee

Journal of Antimicrobial Chemotherapy, dkz133, https://doi.org/10.1093/jac/dkz133

Published: 29 April 2019

 

Abstract

Background

Imipenem resistance in Pseudomonas aeruginosa most often entails loss of the ‘carbapenem-specific’ porin OprD; more rarely it reflects acquired carbapenemases. Loss of OprD only confers resistance to imipenem if AmpC β-lactamase is expressed, and we investigated whether this mechanism was overcome by relebactam, a developmental diazabicyclooctane β-lactamase inhibitor.

Methods

Consecutive P. aeruginosa isolates causing bacteraemia or hospital-onset lower respiratory tract infections were collected between 2014 and 2016 under the aegis of the BSAC Resistance Surveillance Programme. Imipenem MICs were determined centrally by BSAC agar dilution, with relebactam at a fixed concentration (4 mg/L).

Results

For most imipenem-susceptible P. aeruginosa (726/759, 95.7%), the MICs of imipenem alone were 0.5–2 mg/L and were decreased 3- to 4-fold by addition of relebactam, as based on geometric means or modes. For most imipenem-resistant P. aeruginosa (82/92, 89%), imipenem MICs were 8–16 mg/L, and were reduced to 1–2 mg/L by relebactam. These patterns applied regardless of whether the isolates were susceptible to penicillins and cephalosporins or had phenotypes suggesting derepressed AmpC or up-regulated efflux. Imipenem MICs for five P. aeruginosa with MBLs remained high (≥16 mg/L) regardless of relebactam.

Conclusions

Potentiation of imipenem by relebactam was almost universal, in accordance with the view that endogenous pseudomonal AmpC ordinarily protects against this carbapenem to a small degree. Imipenem MICs were reduced to the current breakpoint, or lower, except for MBL producers. Potentiation was not compromised by derepression of AmpC or up-regulation of efflux.

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Drugs Resistance; Pseudomonas aeruginosa; Imipenem; Relebactam.

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Published by

Giuseppe Michieli

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.

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