The mechanism by which beta-lactamase-producing organisms resist ampicillin, and how sulbactam overcomes this resistance, involves which biochemical sequence?

• A Beta-lactamase methylates ampicillin; sulbactam chelates the metal cofactor of the enzyme
• B Beta-lactamase pumps ampicillin out via efflux; sulbactam blocks the efflux pump
• C Beta-lactamase modifies PBP2a to reduce ampicillin affinity; sulbactam restores PBP2a sensitivity
• D Beta-lactamase hydrolyses the beta-lactam ring of ampicillin; sulbactam competitively inhibits beta-lactamase as an irreversible suicide substrate, protecting ampicillin ✓

Explanation

Beta-lactamases are serine-hydrolases that cleave the C-N bond of the beta-lactam ring, inactivating ampicillin. Sulbactam (and clavulanic acid, tazobactam) are beta-lactamase inhibitors that act as 'mechanism-based' (suicide) inhibitors — they bind irreversibly to the active serine residue of the enzyme, permanently inactivating it and allowing co-administered ampicillin to reach its target PBP. This is distinct from efflux-mediated resistance (e.g., in Pseudomonas) or PBP2a-mediated resistance (MRSA), which sulbactam cannot overcome.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.