Ceftazidime-avibactam is effective against KPC-producing Klebsiella pneumoniae but NOT against organisms producing NDM-1 metallo-beta-lactamase. Which pharmacological property of avibactam explains this limitation?

• A Avibactam is a non-beta-lactam inhibitor that covalently inactivates serine-beta-lactamases but cannot inhibit zinc-dependent metallo-beta-lactamases ✓
• B Avibactam is rapidly hydrolyzed by metallo-beta-lactamases before it can inhibit them
• C Avibactam requires active transport into bacteria, which is absent in NDM-producing organisms
• D NDM-1 producers overexpress PBP3 which avibactam cannot inhibit

Explanation

Avibactam is a diazabicyclooctane (DBO) non-beta-lactam beta-lactamase inhibitor that forms a covalent reversible acyl-enzyme complex with serine-active-site beta-lactamases (class A: KPC, ESBL; class C: AmpC; some class D: OXA). Metallo-beta-lactamases like NDM-1 (New Delhi Metallo-beta-lactamase-1) use zinc ions in their active site and are classified as class B — they have a fundamentally different catalytic mechanism with no serine residue for avibactam to target. Aztreonam-avibactam is used for NDM producers as aztreonam is not hydrolyzed by metallo-beta-lactamases.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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