A 70-year-old man with creatinine clearance of 15 mL/min receives high-dose imipenem for a ventilator-associated pneumonia. On day 3 he develops myoclonus progressing to generalized seizures. The most likely explanation is:
- A An immune-mediated encephalitis caused by the infecting organism
- B Cilastatin-induced cerebral vasculitis
- C Accumulation of imipenem due to reduced renal clearance, lowering the seizure threshold ✓
- D Hyponatremia from inappropriate ADH secretion triggered by meropenem
Correct answer: C. Accumulation of imipenem due to reduced renal clearance, lowering the seizure threshold
Explanation
Imipenem lowers the seizure threshold more than other carbapenems, and neurotoxicity is strongly dose-related. In renal failure the drug accumulates because it is primarily renally cleared, so doses must be adjusted to creatinine clearance. The proposed mechanism is impaired GABA binding at postsynaptic sites. Meropenem and ertapenem carry a lower seizure risk and are preferred when CNS infection or severe renal impairment coexists. Cilastatin is a renal dehydropeptidase inhibitor and has no neurological effects.
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.