Table 1.

List of important BLIs, their class, inhibition spectrum, and clinical status.

Class of β-lactamase inhibitor	Inhibitor	Partner β-lactams	Inhibition spectrum	Current status	Isolated from	References
First generation
Irreversible acylation of catalytic serine residue	Clavulanic acid	Amoxicillin, Ticarcillin	Plasmid encoded Class A ESBLs	Completed, marketed as Augmentin®, Timentin®	Streptomyces clavuligerus	Bush (1988)
Penicillin-based sulfones	Sulbactam	Ampicillin, Piperacillin, Amoxicillin, Cefoperazone	Primarily to Class A (TEM-type β-lactamases), less effective against SHV and OXA-type β-lactamases	Completed, marketed as Unasyn®	Synthetic	Benson and Nahata (1988)
	Tazobactam (YTR 830)	Piperacillin, Ceftolozane	Class A ESBLs (TEM, SHV), Class C enzymes and OXA-type β lactamases	Completed, marketed as Zosyn®	Synthetic derivative of penicillin	Wise et al. (1991) and Bush (2015)
Second generation
Diazabicyclooctane (DABCO)	Avibactam (AVE1330A, NZL 104)	Ceftaroline, Ceftazidime, Aztreonam	Class A ESBLs (TEM, KPC and SHV) Class A carbapenemases, Class C and D enzymes,	Completed, marketed as Avycaz®, Zavicefta®	Synthetic	Bonnefoy (2004) and Ehmann et al. (2012)
	Relebactam (MK-7655)	Imipenem	Class A ESBLs, Class A carbapenemases Class C enzymes	Completed, marketed as Recarbrio®	Synthetic	Blizzard et al. (2014) and FDA (2019)
Third generation
Boronic acid inhibitor	Vaborbactam	Biapenem, Meropenem, Doripenem, Ertapenem	Broad spectrum of class A (KPC, CTX-M, SHV), C (CMY) and D enzymes	Completed phase III trials, marketed as Vabomere™, Carbavance®	Synthetic	Hecker et al. (2015)
	(VNRX-5133)	Cefepime	Class A, C and D serine β lactamases and class B MBLs (VIM and NDM) in both carbapenem-resistant Enterobacteriaceae and P. aeruginosa	Undergoing phase III drug–drug interaction study	Synthetic	Liu et al. (2020)
Bicyclo-acyl hydrazide	Zidebactam (WCK 5107)	Cefepime	AmpC, ESBL, KPC, and OXA-48-like β-lactamases	Under phase III clinical trials	Synthetic	Yahav et al. (2020) and Karlowsky et al. (2020)
Diazabicyclooctane	Nacubactam (OP0595, RO7079901, RG6080)	Meropenem	Class A, Class C and some Class D β-lactamases and against carbapenem-resistant K. pneumoniae	Phase I clinical trial completed	Synthetic	Mallalieu et al. (2020)
Diazabicyclooctane	Durlobactam (ETX2514)	Sulbactam	Class A, C and D serine β-lactamases.	Phase III clinical trial completed	Synthetic	Shapiro et al. (2021)
Diazabicyclooctane	ETX1317/ Prodrug ETX0282	Cefpodoxime proxetil	Class A, C, and D serine β-lactamases	Phase I clinical trial completed	Synthetic	Durand-Réville et al. (2020)
Penicillanic acid sulfone	Enmetazobactam (AAI101)	Cefepime	CTX-M, TEM, SHV, and other class A β-lactamases	Phase III clinical trial completed	Synthetic	Papp-Wallace et al. (2019)
Metallo-beta-lactamases (MBL) inhibitors	Elores (CSE:1034)	Ceftriaxone, sulbactam, disodium edetate (EDTA)	MBLs	Completed, marketed in India as Elores	EDTA	Chaudhary et al. (2017)
	ANT 431	Meropenem	MBLs and MBL-producing carbapenem resistant Enterobacteriaceae (CRE)	Undergoing clinical trials	Synthetic	Everett et al. (2018)
	QPX7728	Meropenem	VIM-1, NDM-1 and IMP-1	Under phase I clinical trials	Synthetic	Lomovskaya et al. (2021)
	Magnolol	Meropenem	NDM	Undergoing clinical trials	Magnolia officinalis	Liu et al. (2018)
	Aspergillomarasmine A	Meropenem	NDM-1 enzyme and other MBLs, VIM-2	Undergoing clinical trials	Aspergillus versicolor	King et al. (2014)
	Bisthiazolidines	Meropenem	Class B1,B2 and B3 MBLs	Undergoing laboratory studies	Synthetic	Hinchliffe et al. (2016)
	Nitrilotriacetic acid and N-(phosphonomethyl)iminodiacetic acid	Meropenem	VIM, NDM and IMP classes		6-phosphonomethylpyridine-2-carboxylates	Tehrani et al. (2020)