The current epidemic of multidrug-resistant (MDR) bacterial infections is a critical challenge in health care today. A common mechanism of resistance is the production of β-lactamases, which can often be overcome by the coadministration of a β-lactamase inhibitor with a β-lactam antibiotic. The KPC-2 β-lactamase is the most prevalent carbapenemase in carbapenem-resistant Enterobacteriaceae (CRE) in the United States. KPC-2’s spectrum of activity includes all currently available β-lactams and clavulanic acid, sulbactam, and tazobactam. Fortunately, KPC-2 is susceptible to inhibition by diazabicyclooctane (DBO) β-lactamase inhibitors. Relebactam is a DBO that promises to contribute to the renaissance in antimicrobial chemotherapy. When combined with imipenem, Relebactam is effective against Enterobacteriaceae with known KPC carbapenemases, AmpCs, and/or extended-spectrum β-lactamases (ESBLs).
Relebactam is a parenteral, small-molecule β-lactamase inhibitor that is active against both class A and class C β-lactamases. In vitro susceptibility and hollow-fiber time-kill studies, Relebactam also restores imipenem susceptibility to many imipenem-resistant isolates of AmpC-producing P. aeruginosa and Enterobacteriaceae expressing KPCs or combinations of impermeability and extended-spectrum ESBLs/AmpC. Furthermore, Relebactam given with imipenem-cilastatin has the potential to effectively treat severe Gram-negative bacterial infections in vivo infection models with imipenem-resistant P. aeruginosa and K. pneumonia.
In summary, Relebactam is a β-lactamase inhibitor. It has the ability to inhibit a broad spectrum of β-lactamases. Moreover, it contains class A and class C β-lactamases, including carbapenemases. Moreover, the addition of Relebactam to imipenem restores imipenem activity against several imipenem-resistant bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa. In addition, Imipenem-Cilastatin-Relebactam is a novel β-lactam-β-lactamase inhibitor combination for the treatment of multidrug-resistant gram-negative infections.
Papp-Wallace KM, et al. Antimicrob Agents Chemother. 2018;62(6):e00174-18. Published 2018 May 25.; Smith JR, et al. Pharmacotherapy. 2020;40(4):343-356.