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.
Relebactam是一种β-内酰胺酶（AmpC）抑制剂，能够不可逆地抑制 A类（超广谱β内酰胺酶和KPC酶）和C类AmpC[1]。Relebactam属于二氮杂双环辛烷衍生物，通过共价结合β-内酰胺酶的活性位点丝氨酸残基，不可逆抑制其水解β-内酰胺类抗生素的能力，从而恢复亚胺培南对产酶耐药菌的杀菌活性[2]。Relebactam与亚胺培南（Imipenem）联用能够显著降低最小抑菌浓度（MIC），提升对耐药菌（如铜绿假单胞菌、肺炎克雷伯菌）的疗效[3, 4]。Relebactam能够降低多种头孢菌素和碳青霉烯对脓肿分枝杆菌（Mycobacterium abscessus）的MIC[5]。