A 70-year-old woman with a creatinine clearance of 15 mL/min receives high-dose imipenem-cilastatin for a ventilator-associated pneumonia. On day three she develops generalized tonic-clonic seizures. Which feature most strongly predisposed her to this complication?

• A Concurrent cilastatin administration raised brain imipenem levels
• B Imipenem displaces bilirubin and precipitates kernicterus-related seizures
• C Imipenem causes direct cortical necrosis at therapeutic doses
• D Renal impairment caused drug accumulation, and imipenem lowers the seizure threshold more than other carbapenems ✓

Explanation

Imipenem is the carbapenem with the greatest propensity for seizures, mediated by GABA-A antagonism at high brain concentrations. Risk rises sharply with renal failure, high doses and CNS lesions, so dose adjustment for creatinine clearance is mandatory. Meropenem and ertapenem carry substantially lower seizure risk. Cilastatin only blocks renal dehydropeptidase I and does not enter the CNS. Kernicterus is irrelevant in adults. In such patients, meropenem is the safer carbapenem choice.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.