New Perspectives on Antimicrobial Agents: Imipenem-Relebactam.
Issue Date
7/19/2022
Authors
O'Donnell, J Nicholas
Lodise, Thomas P
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Abstract
Imipenem (IMI)/cilastatin/relebactam (REL) (I/R) is a novel β-lactam/β-lactamase inhibitor combination with expanded microbiologic activity against carbapenem-resistant non- (CR-NME) and difficult-to-treat (DTR) Pseudomonas aeruginosa. Relebactam, a bicyclic diazabicyclooctane, has no direct antimicrobial activity but provides reliable inhibition of many Ambler class A and class C enzymes. It is currently approved for the treatment of adult patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) and those with complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) when limited or no alternative treatments are available. Given the number of recently approved β-lactams with expanded activity against highly resistant Gram-negative pathogens, this review summarizes the published literature on I/R, with a focus on its similar and distinguishing characteristics relative to those of other recently approved agents. Overall, available data support its use for the treatment of patients with HABP/VABP, cUTI, and cIAI due to CR-NME and DTR P. aeruginosa. Data indicate that I/R retains some activity against CR-NME and DTR P. aeruginosa isolates that are resistant to the newer β-lactams and vice versa, suggesting that susceptibility testing be performed for all the newer agents to determine optimal treatment options for patients with CR-NME and DTR P. aeruginosa infections. Further comparative PK/PD and clinical studies are warranted to determine the optimal role of I/R, alone and in combination, for the treatment of patients with highly resistant Gram-negative infections. Until further data are available, I/R is a potential treatment for patients with CR-NME and DTR P. aeruginosa infections when the benefits outweigh the risks.
Citation
O'Donnell JN, Lodise TP. New Perspectives on Antimicrobial Agents: Imipenem-Relebactam. Antimicrob Agents Chemother. 2022 Jul 19;66(7):e0025622. doi: 10.1128/aac.00256-22. Epub 2022 Jun 21. PMID: 35727059; PMCID: PMC9295581.
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The authors declare a conflict of interest. T.P.L. has received consultant honoraria and investigator-initiated grant support from Merck & Co. J.N.O. has received investigator-initiated grant support from Merck & Co.