Ertapenem-Induced Neurotoxicity: A Literature Review of Clinical Characteristics and Treatment Outcomes

Abstract

Background Neurotoxicity is a rare adverse event for ertapenem. Given the limited evidence, large patient data are needed to aid in the identification and management of this fatal complication. Aim of the review, we summarize the characteristics, risk factors, and treatment of ertapenem-induced neurotoxicity. Methods Pubmed, Web of Science, Embase, Cochrane library, Wanfang, CNKI, China VIP database were searched up from 31 October 2001 to 31 December 2022. All articles concerning neurotoxicity induced by ertapenem were included. The retrieved articles were screened by two experienced clinicians by reading the titles, abstracts, and full texts. Results A total of 66 patients were included, with a median age of 71.5 years (range 40–92), of whom 45 (68.2%) were male. Twelve patients (18.2%) received irrational doses (exceeding the recommended dose), and 30 patients (45.5%) had chronic renal insufficiency. The median time to symptom onset was 5 (range 1–14). Epileptiform seizures (42.4%), visual hallucinations (36.4%), altered mental status (25.8%), and confusion (22.7%) were the most common symptoms of ertapenem-induced neurotoxicity. Of the 29 patients with reported albumin levels, 25 had serum albumin <3.5 g/dl. Ertapenem was discontinued in 95.5% of patients, and 90.9% recovered completely. Median time to symptom recovery was 7 days (range 1–42) after intervention including antiepileptic administration, or hemodialysis. Conclusion Neurotoxicity is a rare adverse event for ertapenem, especially in patients with advanced age, renal insufficiency, pre-existing neurological disease, and hypoalbuminemia. This adverse reaction usually resolves with medication interruption, or antiepileptic administration and hemodialysis.

A Rare Case of Late-Onset Ertapenem-Induced Encephalopathy

“…Rarely, prolonged therapy may lead to drug accumulation despite normal renal function, resulting in delayed symptom onset, as in this case [ 10 ]. Additionally, low serum albumin at the time ertapenem is started has been associated with developing encephalopathy [ 8 ]. As ertapenem is highly protein-bound, low levels of albumin may lead to higher serum concentrations of free ertapenem, thus increasing the risk for adverse reactions [ 11 ].…”

“…Seizures are the most common manifestation, but patients may also present with agitation, delirium, and insomnia symptoms, usually within one week of initiating therapy [2,3,5]. Risk factors for carbapenem-induced encephalopathy include renal impairment, low serum albumin, and prior central nervous system (CNS) injury [6][7][8]. Ertapenem-induced encephalopathy is often reversible, typically within 48 hours of drug cessation; however, recovery may be delayed up to two weeks in patients with severe renal dysfunction [2,5,9,10].…”

Ertapenem-induced encephalopathy in a patient with liver abscess and acute kidney injury

“…Epileptiform seizures (42.4%), visual hallucinations (36.4%), altered mental status (25.8%) and confusion (22.7%) were the most common symptoms of ertapenem-induced neurotoxicity. 7 We report a patient with normal cognitive function admitted with a liver abscess and acute kidney injury who developed ertapenem-induced encephalopathy.…”

“…For ertapenem, neurotoxicity is a rare adverse event, especially in patients with advanced age, renal insufficiency, pre-existing neurological disease and hypoalbuminaemia. Epileptiform seizures (42.4%), visual hallucinations (36.4%), altered mental status (25.8%) and confusion (22.7%) were the most common symptoms of ertapenem-induced neurotoxicity 7. We report a patient with normal cognitive function admitted with a liver abscess and acute kidney injury who developed ertapenem-induced encephalopathy.…”