A patient with a KPC-producing Klebsiella pneumoniae bloodstream infection is being considered for ceftazidime-avibactam therapy. Avibactam is a novel beta-lactamase inhibitor. Which class of carbapenemases does avibactam inhibit, and which does it NOT inhibit?

• A Inhibits: KPC (class A), OXA-48 (class D), MBLs partially; Does NOT inhibit: NDM, VIM (class B MBLs) effectively
• B Inhibits: KPC and OXA-48 only; Does NOT inhibit: MBLs or class C AmpC enzymes ✓
• C Inhibits: NDM, VIM, IMP (all class B MBLs); Does NOT inhibit: KPC or OXA-type
• D Inhibits all Ambler classes A, B, C, D equally through covalent active-site binding

Explanation

Avibactam is a diazabicyclooctane (DBO) non-beta-lactam beta-lactamase inhibitor that covalently and reversibly inhibits Ambler class A (including KPC, TEM, SHV, CTX-M, SME), class C (AmpC), and class D (OXA-48-like) carbapenemases. Critically, avibactam does NOT inhibit class B metallo-beta-lactamases (NDM, VIM, IMP) because these require zinc cofactors in their active site and have a different catalytic mechanism that avibactam cannot target. Ceftazidime-avibactam is therefore inactive against NDM-producing organisms. Aztreonam-avibactam combinations are being developed to cover NDM producers. This distinction is clinically critical when choosing therapy for CRE infections.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.