From the FDA Drug Label
Encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, and non-convulsive status epilepticus have been reported Although most cases occurred in patients with renal impairment who received doses of cefepime that exceeded the recommended dosage schedules, some cases of neurotoxicity occurred in patients receiving an appropriate dosage adjustment for their degree of renal impairment If neurotoxicity associated with cefepime therapy occurs, consider discontinuing cefepime or making appropriate dosage adjustments in patients with renal impairment.
Cefepime-induced encephalopathy is a potential adverse event associated with the use of cefepime, particularly in patients with renal impairment.
- The exact mechanism of this adverse event is not specified in the drug label.
- Neurotoxicity can occur even when patients receive the recommended dosage adjustment for their degree of renal impairment.
- Patients should be monitored for signs and symptoms of encephalopathy, including confusion, hallucinations, stupor, and coma, and the drug should be discontinued or the dosage adjusted if neurotoxicity occurs 1.
From the Research
Cefepime-induced encephalopathy is a serious neurological adverse effect that can occur in patients receiving the antibiotic cefepime, particularly in those with renal impairment, and if suspected, the drug should be immediately discontinued and alternative antibiotics considered. This condition typically presents with altered mental status, confusion, disorientation, myoclonus, seizures, and in severe cases, coma. The risk is significantly higher in patients with decreased kidney function, as cefepime is primarily eliminated through the kidneys, leading to drug accumulation when renal clearance is reduced 2.
Risk Factors and Diagnosis
Key risk factors for cefepime-induced encephalopathy include renal dysfunction, excessive dosing, preexisting brain injury, and elevated serum cefepime concentrations 3. The diagnosis can be challenging, especially in critically ill patients, due to the wide range of symptoms that are common in ICU patients. EEG findings often show diffuse slowing or triphasic waves, which can help in diagnosis 3.
Management and Prevention
Dose adjustment based on creatinine clearance is essential when using cefepime in patients with renal impairment. For example, patients with a creatinine clearance of 30-50 mL/min should receive 1-2g every 24 hours instead of the standard 1-2g every 12 hours. Symptoms typically improve within 2-7 days after discontinuation of cefepime 2. Hemodialysis may be considered in severe cases to enhance drug clearance, as seen in a case where a pediatric patient with end-stage renal disease experienced rapid reversal of symptoms after high-efficiency hemodialysis 4.
Clinical Considerations
It is crucial for clinicians to recognize the possibility of cefepime-induced encephalopathy, especially in high-risk patients, and to monitor them closely for neurological symptoms. The condition can occur despite appropriate dosing and usually resolves with drug interruption but may require additional interventions such as antiepileptic drug administration or dialysis 3. Even patients with normal renal function can be at risk, as highlighted by a case of cefepime-associated encephalopathy in a patient with normal renal function 5.
Outcome and Quality of Life
The outcome for patients with cefepime-induced encephalopathy is generally good if the condition is recognized and treated promptly. Most patients experience improvement in symptoms after discontinuation of cefepime, with a significant proportion surviving to hospital discharge 3. However, delayed recognition and treatment can lead to poorer outcomes, emphasizing the need for vigilance and prompt action when cefepime-induced encephalopathy is suspected.