Which of the following best explains why carbapenems (e.g., imipenem) have the broadest beta-lactam spectrum including activity against ESBL-producing organisms while classic penicillins fail?
- A Carbapenems inhibit outer membrane porins preventing beta-lactamase access
- B Carbapenems bind PBPs with 100-fold higher affinity than penicillins
- C Carbapenems have a 1-beta-methyl group giving them resistance to hydrolysis by most beta-lactamases including ESBLs ✓
- D Carbapenems are prodrugs activated intracellularly after entering the periplasm
Correct answer: C. Carbapenems have a 1-beta-methyl group giving them resistance to hydrolysis by most beta-lactamases including ESBLs
Explanation
The unique bicyclic structure of carbapenems — specifically the trans configuration at position 6 and the 1-beta-methyl substituent (in meropenem/doripenem) or the methylene bridge — renders the beta-lactam ring highly resistant to hydrolysis by ESBLs and most other beta-lactamases. Imipenem lacks the methyl group but still resists ESBL hydrolysis due to its structural conformation. Only metallo-beta-lactamases (NDM, VIM, IMP) can cleave carbapenems reliably.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.