From the Guidelines
Ertapenem-induced neurotoxicity is a significant risk that primarily affects patients with renal impairment, and dosage adjustment is crucial to minimize this risk. The presentation of ertapenem-induced neurotoxicity typically includes confusion, hallucinations, myoclonus, seizures, and altered mental status, which usually develop within 1-10 days of starting treatment 1. According to the guidelines from the French Society of Pharmacology and Therapeutics and the French Society of Anaesthesia and Intensive Care Medicine, it is suggested that exceeding plasma free concentrations of beta-lactam antibiotics, such as ertapenem, above eight times the MIC is useless and even dangerous 1.
Risk Factors
The main risk factor associated with neurological toxicity of beta-lactam antibiotics, including ertapenem, is renal failure, which may cause rapid and significant accumulation of the drug 1. Other risk factors include advanced age, CNS disorders, and higher doses.
Dosage Adjustment
To minimize the risk of neurotoxicity, dosage adjustment is essential for patients with creatinine clearance below 30 mL/min, with a recommended dose of 500 mg daily instead of the standard 1 g daily. Close monitoring of neurological function is crucial, especially in high-risk patients.
Mechanism and Management
The mechanism behind ertapenem-induced neurotoxicity involves the drug crossing the blood-brain barrier and inhibiting GABA receptors, leading to CNS excitation. If symptoms develop, immediate discontinuation of ertapenem is recommended, with symptoms typically resolving within 24-72 hours after stopping the medication. Alternative antibiotics like meropenem or imipenem may be considered for patients with a history of carbapenem-induced neurotoxicity, though cross-reactivity can occur. Hemodialysis can accelerate ertapenem clearance in severe cases with renal impairment.
Key Considerations
- Renal impairment is a significant risk factor for ertapenem-induced neurotoxicity
- Dosage adjustment is crucial for patients with creatinine clearance below 30 mL/min
- Close monitoring of neurological function is essential, especially in high-risk patients
- Immediate discontinuation of ertapenem is recommended if symptoms of neurotoxicity develop 1.
From the FDA Drug Label
5.2 Seizure Potential Seizures and other central nervous system (CNS) adverse experiences have been reported during treatment with ertapenem for injection [see Adverse Reactions (6. 1)]. During clinical investigations in adult patients treated with ertapenem for injection (1 g once a day), seizures, irrespective of drug relationship, occurred in 0.5% of patients during study therapy plus 14-day follow-up period [see Adverse Reactions (6.1)]. These experiences have occurred most commonly in patients with CNS disorders (e.g., brain lesions or history of seizures) and/or compromised renal function. Close adherence to the recommended dosage regimen is urged, especially in patients with known factors that predispose to convulsive activity. Anticonvulsant therapy should be continued in patients with known seizure disorders If focal tremors, myoclonus, or seizures occur, patients should be evaluated neurologically, placed on anticonvulsant therapy if not already instituted, and the dosage of ertapenem for injection re-examined to determine whether it should be decreased or discontinued.
The risk of neurotoxicity associated with ertapenem includes seizures and other central nervous system (CNS) adverse experiences.
- Presentation: Seizures, focal tremors, myoclonus.
- Risk factors: CNS disorders (e.g., brain lesions or history of seizures) and/or compromised renal function.
- Precautions: Close adherence to the recommended dosage regimen, continuation of anticonvulsant therapy in patients with known seizure disorders, and evaluation of patients with seizures or other CNS adverse experiences. 2 2 2
From the Research
Risk Factors for Ertapenem-Induced Neurotoxicity
- Advanced age 3
- Renal insufficiency, particularly in patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) 4, 5, 3, 6, 7
- Pre-existing neurological disease 3
- Hypoalbuminemia 3, 6
- Use of excessive doses, especially in patients with moderate renal failure 5, 6
Presentation of Ertapenem-Induced Neurotoxicity
- Epileptiform seizures (42.4% of cases) 3
- Visual hallucinations (36.4% of cases) 3
- Altered mental status (25.8% of cases) 3
- Confusion (22.7% of cases) 3
- Delirium 7
- Agitation 7
- Encephalopathy 7
Management and Treatment Outcomes
- Discontinuation of ertapenem is often effective in resolving neurotoxicity symptoms 4, 3, 7
- Antiepileptic administration may be necessary in some cases 3
- Hemodialysis may be used to reduce ertapenem levels in patients with renal failure 5, 3
- Median time to symptom recovery is 7 days (range 1-42) after intervention 3