A 70-year-old woman with a creatinine clearance of 20 mL/min receives imipenem-cilastatin for a ventilator-associated pneumonia. On day three she develops myoclonus progressing to generalized seizures. The most likely contributing factor is:

• A An allergic vasculitis of the cerebral circulation caused by the carbapenem nucleus
• B Cilastatin crossing the blood-brain barrier and inhibiting CNS GABA transaminase
• C Accumulation of imipenem due to inadequate dose reduction for renal impairment ✓
• D Hyponatremia secondary to cilastatin-induced syndrome of inappropriate ADH secretion

Explanation

Carbapenems, imipenem in particular, lower the seizure threshold by antagonizing GABA-C receptors, and this risk rises sharply when high drug levels accumulate in patients with renal failure whose doses are not adjusted. Meropenem carries a lower seizure risk. Cilastatin acts peripherally as a renal dehydropeptidase inhibitor and does not enter the CNS, so B is incorrect.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.