A patient with Gram-negative sepsis is started on imipenem-cilastatin. What is the PRIMARY purpose of combining imipenem with cilastatin?

• A Cilastatin inhibits beta-lactamase produced by bacteria, broadening imipenem's spectrum
• B Cilastatin increases oral bioavailability of imipenem by inhibiting intestinal transport
• C Cilastatin competes with imipenem for the active site of PBP2a, restoring activity against MRSA
• D Cilastatin inhibits renal dehydropeptidase-1, preventing nephrotoxic metabolism of imipenem ✓

Explanation

Imipenem is hydrolyzed by renal dehydropeptidase-1 (DHP-1) in the proximal tubule to nephrotoxic metabolites, significantly reducing urinary concentrations. Cilastatin is a DHP-1 inhibitor that blocks this metabolism, preventing nephrotoxicity and maintaining adequate urinary levels of active imipenem. Meropenem and ertapenem are stable to DHP-1 and do not require such a combination. Cilastatin has no beta-lactamase inhibitory or PBP activity.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.