Relebactam Is a Potent Inhibitor of the KPC-2 beta-Lactamase and Restores Imipenem Susceptibility in KPC-Producing Enterobacteriaceae.

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Papp-Wallace KM, Barnes MD, Alsop J, Taracila MA, Bethel CR, Becka SA, van Duin D, Kreiswirth BN, Kaye KS, Bonomo RA

Relebactam Is a Potent Inhibitor of the KPC-2 beta-Lactamase and Restores Imipenem Susceptibility in KPC-Producing Enterobacteriaceae.

Antimicrob Agents Chemother. 2018 May 25;62(6). pii: AAC.00174-18. doi: 10.1128/AAC.00174-18. Print 2018 Jun.

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29610205 [ View in PubMed
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Abstract

The imipenem-relebactam combination is in development as a potential treatment regimen for infections caused by Enterobacteriaceae possessing complex beta-lactamase backgrounds. Relebactam is a beta-lactamase inhibitor that possesses the diazabicyclooctane core, as in avibactam; however, the R1 side chain of relebactam also includes a piperidine ring, whereas that of avibactam is a carboxyamide. Here, we investigated the inactivation of the Klebsiella pneumoniae carbapenemase KPC-2, the most widespread class A carbapenemase, by relebactam and performed susceptibility testing with imipenem-relebactam using KPC-producing clinical isolates of Enterobacteriaceae MIC measurements using agar dilution methods revealed that all 101 clinical isolates of KPC-producing Enterobacteriaceae (K. pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, Citrobacter koseri, and Escherichia coli) were highly susceptible to imipenem-relebactam (MICs

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