Ceftazidime-avibactam is effective against KPC-producing Klebsiella pneumoniae (CRKP) because avibactam:
- A Is a beta-lactam with intrinsic activity against KPC and irreversibly inhibits the enzyme
- B Chelates zinc ions in the active site of KPC class A enzyme, rendering it catalytically inactive
- C Restores ceftazidime outer membrane permeability by inhibiting porin downregulation in CRKP
- D Is a non-beta-lactam BLI that covalently but reversibly carbamylates the KPC serine active site, preserving avibactam for recycling ✓
Explanation
Avibactam is a diazabicyclooctane (DBO) non-beta-lactam beta-lactamase inhibitor that acylates serine beta-lactamases (class A including KPC, class C AmpC, and some class D OXA) through a covalent carbamylation reaction that is reversible (avibactam can deacylate and regenerate active inhibitor). This recycling is clinically important as it provides sustained inhibition. Avibactam does NOT inhibit metallo-beta-lactamases (MBL, class B — e.g., NDM), which require zinc chelation-based inhibitors. Zinc chelation is the mechanism of ceftazidime-aztreonam combination against MBL producers.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.