Seizures associated with ertapenem use in patients with CNS disorders and renal insufficiency

Abstract

Three patients presented seizures during ertapenem therapy. They were classified as probably-related in 1 case and as possible-related in the others. Convulsions appeared after 1 week of therapy at usual doses with 1 or 2 events, and were observed only among patients with CNS disorders and renal insufficiency.

Status Epilepticus and Delirium Associated with Ertapenem in a Very Elderly Patient with Chronic Kidney Disease and Silent Ischaemic Cerebrovascular Disease

“…The number of days-to-onset of our patient’s first seizure (8 days) with the first course of ertapenem was consistent with that reported in various case reports [3, 4, 9, 11]. With re-exposure to ertapenem, her seizures recurred despite being on an anti-epileptic drug.…”

“…The half-life of ertapenem is about 4.5 h in healthy individuals but it can be increased to 6.1–14.1 h in the presence of chronic renal impairment [12, 14]. Some degree of renal dysfunction has been reported in a number of cases of neurotoxicity associated with ertapenem use [3, 11, 14–16]. It has been proposed that in the presence of uraemia, the blood–brain barrier is also more permeable and the protein binding of antibacterials is decreased [4, 11].…”

“…Some degree of renal dysfunction has been reported in a number of cases of neurotoxicity associated with ertapenem use [3, 11, 14–16]. It has been proposed that in the presence of uraemia, the blood–brain barrier is also more permeable and the protein binding of antibacterials is decreased [4, 11]. In addition, with the accumulation of endogenous uraemic toxins, a patient may then be more vulnerable to antibiotic-related neurotoxicity [4].…”

Use of Monte Carlo Simulations to Determine Optimal Carbapenem Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy

“…No data yet exist to define carbapenem exposure and the toxicity concentration threshold. However, carbapenem toxicity has been well documented with higher carbapenem doses (4 g/day) or in patients with severe renal insufficiency . Thus, optimal dosing regimens were defined as those achieving ≥90% PTA with the smallest daily dose to minimize the risk of toxicity.…”

“…However, carbapenem toxicity has been well documented with higher carbapenem doses (4 g/day) or in patients with severe renal insufficiency. 55,56 Thus, optimal dosing regimens were defined as those achieving ࣙ90% PTA with the smallest daily dose to minimize the risk of toxicity. In addition, sensitivity analyses were performed to investigate the influence of different PIRRT regimens on carbapenem dosing in PIRRT.…”