Beta-lactamase inhibitors

Clavams (Classical β-lactam-structured inhibitors)

Inhibitor	Structure type	Mechanism	Effective vs β-lactamase class	Unique features
Clavulanic acid	β-lactam (oxazolidine ring)	Irreversible suicide substrate	Class A (TEM, SHV); weak vs C/D	Only natural inhibitor (from Streptomyces clavuligerus); first marketed (1981)
Sulbactam	β-lactam (penicillanic acid sulfone)	Irreversible acyl-enzyme	Class A > C (limited)	Has intrinsic antibacterial activity vs Acinetobacter spp.
Tazobactam	β-lactam (triazolylmethyl sulfone)	Irreversible	Class A; weak vs C/D	Broader than clavulanate; used with piperacillin, cefepime

Diazabicyclooctane (DBO) inhibitors — non-β-lactam, reversible

Inhibitor	Mechanism	Effective vs Class	Partner Drug(s)	Key Distinction
Avibactam	Reversible covalent acyl-enzyme (non-β-lactam DBO)	A, C, some D (e.g., OXA-48)	Ceftazidime (CZA)	First clinically used non-β-lactam inhibitor
Relebactam	Reversible DBO	A, C (not D)	Imipenem + cilastatin (IMI/REL)	Improved stability vs avibactam
Nacubactam	DBO	A, C (+ intrinsic PBP inhibition)	Meropenem (in trials)	Has dual mechanism (β-lactamase + PBP)
Zidebactam	DBO	A, C (+ PBP2 binding)	Cefepime ( FEP-ZID, in development)	Potent synergy via PBP2 affinity
Enmetazobactam	DBO-like (penicillanic sulfone + triazole)	A (incl. ESBL)	Cefepime (approved EU 2024)	Modified sulfone, faster kinetics

Boronate inhibitors (Transition-state analogues)

Inhibitor	Mechanism	Effective vs Class	Partner	Notes
Vaborbactam	Reversible boronate transition-state mimic	A (esp. KPC), not C/D	Meropenem (→ MER/VAB)	Potent against KPC carbapenemases
Taniborbactam	Cyclic boronate	A, C, D, some B (NDM)	Cefepime (→ phase 3 trials)	Broadest coverage (incl. MBL NDM partial)
QPX7728	Ultrawide-spectrum boronate	A, C, D, some B	In development (oral β-lactams)	Designed for oral combinations

Miscellaneous or Investigational

Inhibitor	Type	Stage	Coverage
LN-1-255	Monobactam-based inhibitor	Pre-clinical	A > C
ETX0282	Oral prodrug of DBO (ETX1317)	Phase 2	A, C