Relebactam

Relebactam is a β-lactamase (AmpC) inhibitor that can irreversibly inhibit Class A (extended-spectrum β-lactamase and KPC enzymes) and Class C AmpC^[1]. Relebactam is a diazabicyclooctane derivative that covalently binds to the active site serine residue of β-lactamase, irreversibly inhibiting its ability to hydrolyze β-lactam antibiotics, thereby restoring the bactericidal activity of imipenem against enzyme-producing resistant bacteria^[2]. The combination of Relebactam and Imipenem can significantly reduce the minimum inhibitory concentration (MIC) and improve the efficacy against resistant bacteria (such as Pseudomonas aeruginosa and Klebsiella pneumoniae)^{[3, 4]}. Relebactam can reduce the MIC of multiple cephalosporins and carbapenems against Mycobacterium abscessus^[5].

References:
[1] Alfei S, Schito A M. β-lactam antibiotics and β-lactamase enzymes inhibitors, part 2: our limited resources[J]. Pharmaceuticals, 2022, 15(4): 476.
[2] Tooke C L, Hinchliffe P, Lang P A, et al. Molecular basis of class A β-lactamase inhibition by relebactam[J]. Antimicrobial agents and chemotherapy, 2019, 63(10): 10.1128/aac. 00564-19.
[3] McCarthy M W. Clinical Pharmacokinetics and Pharmacodynamics of Imipenem–Cilastatin/Relebactam Combination Therapy[J]. Clinical Pharmacokinetics, 2020, 59(5): 567-573.
[4] Young K, Painter R E, Raghoobar S L, et al. In vitro studies evaluating the activity of imipenem in combination with relebactam against Pseudomonas aeruginosa[J]. BMC microbiology, 2019, 19: 1-14.
[5] Kaushik A, Ammerman N C, Parrish N M, et al. New β-lactamase inhibitors nacubactam and zidebactam improve the in vitro activity of β-lactam antibiotics against Mycobacterium abscessus complex clinical isolates[J]. Antimicrobial agents and chemotherapy, 2019, 63(9): 10.1128/aac. 00733-19.