Acute prolonged neurotoxicity associated with recommended doses of ertapenem in 2 patients with advanced renal failure

Ertapenem, a novel carbapenem with long-acting antimicrobial activity, is predominantly eliminated by the kidneys. Acute prolonged neurotoxicity associated with recommended doses of ertapenem in patients with advanced renal failure not yet on dialysis has not been reported. Two patients with Stage 5 chronic kidney disease (CKD) developed progressive hallucinations, asterixis, myoclonic jerks, and cognitive impairment after receiving the recommended dose reduction for CKD of ertapenem (500 mg/d) for 4 days (Case 1: acute cholecystitis) and 5 days (Case 2: arteriovenous fistula infection). Exhaustive diagnostic workups were non-revealing. Plasma ertapenem level measured 24 h after the last dose in Patient 2 was 53.7 mg/l, much higher than the therapeutic MIC90 (2 mg/l). Despite the cessation of ertapenem and initiation of high-flux hemodialysis, their neurologic manifestations lasted for 2 weeks. The structural and pharmacokinetic characteristics of ertapenem such as its high lipophilicity, central nervous penetration, and volume of distribution contributed to sustained neurotoxicity even with significant reduction in plasma ertapenem levels by high-flux hemodialysis. Although ertapenem 500 mg/d has been recommended in patients with glomerular filtration rate less than 30 ml/min/1.73 m2, our 2 cases highlight that this dosage might be excessive for patients with Stage 5 CKD, especially those not yet on dialysis.