Table 2.

Latest advances in β-lactam/β-lactam inhibitor combination for treatment of Gram-negative bacterial infections.

Combination	Type of BLI	Potential pathogens covered	Unique features	Development Phase
Ceftolozane-tazobactam	Sulfone	P. aeruginosa, Enterobacteriaceae-producing ESBLs	Targets P. aeruginosa, including MDR strains, carbapenem-sparing	FDA approved (2014)
Ceftazidime-avibactam	DBO	P. aeruginosa, Enterobacteriaceae-producing carbapenemases and ESBLs	First-in-class BLI, targets KPC and OXA-48-producing Enterobacteriaceae	FDA approved (2015)
Meropenem-vaborbactam	Boronate	Enterobacteriaceae-producing carbapenemases and ESBLs	First-in-class BLI, targets KPC-producing Enterobacteriaceae	FDA approved (2017)
Imipenem-cilastatin-relebactam	DBO	P. aeruginosa, Enterobacteriaceae-producing carbapenemases and ESBLs	Targets KPC-producing Enterobacteriaceae and P. aeruginosa	FDA approved (2019)
Aztreonam-avibactam	DBO	Enterobacteriaceae-producing carbapenemases, including metallo-β-lactamases	Activity against metallo-β-lactamase-producing Enterobacteriaceae	Phase 3
Cefepime-enmetazobactam	Sulfone	Enterobacteriaceae-producing ESBLs	Zwitterionic pair and carbapenem-sparing	Phase 3
Sulbactam-durlobactam	DBO	A. baumannii-calcoaceticus complex	Niche agent, targets Acinetobacter spp., and BLI possesses enhanced reactivity, is a β-lactam ‘enhancer’, and inhibits OXAs	Phase 3
Cefepime-tazobactam	Sulfone	Enterobacteriaceae-producing carbapenemases and ESBLs	High dose, extended infusion, carbapenem-sparing	Phase 3
Cefepime-taniborbactam	Boronate	Enterobacteriaceae-producing ESBLs, carbapenemases, including metallo-β-lactamases (except IMP)	Bicyclic boronate, activity against metallo-β-lactamases	Phase 3
Cefepime-zidebactam	DBO	P. aeruginosa, Enterobacteriaceae-producing carbapenemases, including metallo-β-lactamases and ESBLs. Acinetobacter spp.	Inhibits KPC- and metallo-β-lactamase- producing Enterobacteriaceae, BLI is a β-lactam ‘enhancer’ and bicyclo-acyl hydrazide	Phase 1
Meropenem-nacubactam	DBO	Enterobacteriaceae-producing carbapenemases, including metallo-β-lactamases and ESBLs	Inhibits KPC- and metallo-β-lactamase- producing Enterobacteriaceae, BLI is a β-lactam ‘enhancer’	Phase 1
Cefpodoxime-proxetil-ETX0282	DBO	Enterobacteriaceae-producing carbapenemases and ESBLs	Oral stepdown, and BLI possesses enhanced reactivity, is β-lactam ‘enhancer’, and inhibits OXAs	Phase 1
Meropenem-WCK 4234	DBO	Enterobacteriaceae-producing carbapenemases and ESBLs and A. baumannii	Inhibits KPC and OXA-48-producing Enterobacteriaceae and Acinetobacter spp., BLI inhibits OXAs	Preclinical
Ceftibuten-clavulanate	Oxapenem	Enterobacteriaceae-producing ESBLs	Oral stepdown, carbapenem-sparing	Preclinical
Ceftibuten-VNRX-7145	Boronate	Enterobacteriaceae-producing carbapenemases and ESBLs	Oral stepdown, inhibits KPC and OXA-48-producing Enterobacteriaceae	Preclinical
GT-1-GT-055	DBO	P. aeruginosa, Enterobacteriaceae-producing carbapenemases, metallo-β-lactamases, and ESBLs and A. baumannii	Siderophore-cephem and broad spectrum activity; inhibits KPC- and metallo-β-lactamase- producing Enterobacteriaceae,	Preclinical