From the Guidelines
Cefepime-induced neurotoxicity in patients with impaired renal function should be managed by immediately discontinuing cefepime and considering dose adjustment based on creatinine clearance to prevent further accumulation of the drug. The management of cefepime-induced neurotoxicity requires prompt recognition and intervention, as it can manifest as encephalopathy, myoclonus, seizures, or non-convulsive status epilepticus 1. Key strategies include:
- Discontinuation of cefepime upon suspicion of neurotoxicity
- Dose adjustment based on creatinine clearance to prevent accumulation of the drug
- Consideration of hemodialysis to accelerate cefepime clearance in severe cases
- Supportive care with antiepileptic medications like levetiracetam or benzodiazepines to control seizures
- EEG monitoring for diagnosis and management, particularly for non-convulsive status epilepticus
According to the guidelines from the French Society of Pharmacology and Therapeutics and the French Society of Anaesthesia and Intensive Care Medicine, plasma free concentrations of beta-lactam antibiotics, including cefepime, should not exceed eight times the MIC to avoid toxicity 1. A literature review of 37 studies on cefepime neurotoxicity found that the risk of neurotoxicity was higher in patients with impaired renal function, with cefepime trough concentrations above 22 mg/L associated with neurotoxicity in 50% of patients 1. Dose adjustment based on creatinine clearance is essential for prevention, with patients with CrCl <60 mL/min requiring reduced doses. Alternative antibiotics should be selected based on the infection being treated and the patient's renal function.
From the FDA Drug Label
5.2 Neurotoxicity: ... If neurotoxicity associated with cefepime therapy occurs, discontinue cefepime and institute appropriate supportive measures.
Most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment.
The management strategies for cefepime-induced neurotoxicity in patients with impaired renal function include:
- Discontinuation of cefepime
- Institution of appropriate supportive measures
- Adjusting the dose in patients with renal impairment to prevent neurotoxicity, as most cases occurred in patients who did not receive appropriate dosage adjustment 2, 2
From the Research
Management Strategies for Cefepime-Induced Neurotoxicity
Cefepime-induced neurotoxicity is a serious adverse effect that can occur in patients with impaired renal function. The management strategies for this condition include:
- Therapeutic drug monitoring to prevent overdosing 3
- Consideration of alternative therapeutic agents 3, 4
- Awareness of the potential for overestimation of glomerular filtration rate 3
- Use of electronic health record alerts to identify patients at risk of cefepime-induced neurotoxicity 3
- Discontinuation of cefepime treatment if neurotoxicity is suspected 5, 6, 4
- Use of electroencephalogram (EEG) to establish the diagnosis of non-convulsive status epilepticus (NCSE) 5, 6, 7
- Employment of continuous renal replacement therapy, such as haemofiltration, to accelerate cefepime removal in severe cases 7
Risk Factors for Cefepime-Induced Neurotoxicity
The risk factors for cefepime-induced neurotoxicity include:
- Impaired renal function 3, 5, 6, 4, 7
- Advanced age 4
- History of stroke and seizures 6
- Metabolic encephalopathy induced by chronic uremia 4
- Use of concomitant medications that interact with cefepime, such as valproic acid and meropenem 7
Clinical Presentation of Cefepime-Induced Neurotoxicity
The clinical presentation of cefepime-induced neurotoxicity can include: