From the Guidelines
Cefepime toxicity should be managed by immediately discontinuing the medication and providing supportive care, as it can cause severe neurotoxicity, especially in patients with renal impairment, with a strong correlation between the occurrence of seizures and the dose of beta-lactams directly injected in brain ventricles 1. To minimize the risk of cefepime toxicity, it is essential to adjust the dose based on renal function, as patients with renal failure are at higher risk of accumulating the drug and experiencing neurotoxicity.
- Key factors to consider in managing cefepime toxicity include:
- Renal function: Cefepime is primarily eliminated renally, and patients with reduced creatinine clearance are at higher risk of toxicity 1.
- Dose adjustment: Adjusting the dose based on creatinine clearance can help prevent toxicity, with recommended doses including 1-2g every 12h for CrCl 30-50 mL/min, 1g every 24h for CrCl 11-29 mL/min, and 0.5g every 24h for CrCl ≤10 mL/min.
- Monitoring: Regular monitoring of renal function and vigilance for early neurological symptoms can help identify potential toxicity early on.
- EEG: Electroencephalogram (EEG) can be used to diagnose neurotoxicity, showing characteristic triphasic waves or nonconvulsive status epilepticus.
- Prevention of cefepime toxicity is crucial, and plasma free concentrations of beta-lactam antibiotics should not exceed eight times the MIC (i.e., %fT > 8× MIC) to minimize the risk of toxicity 1.
- In patients experiencing unexplained neurological manifestations, temporarily suspending beta-lactam administration and discussing therapeutic drug monitoring (TDM) should be considered to rule out antibiotic toxicity.
- Cefepime trough concentrations above 22 mg/L (when administered by discontinuous infusions) or concentrations at steady state above 35 mg/L (when administered by continuous infusion) have been associated with neurotoxicity in 50% of patients, highlighting the importance of monitoring drug levels 1.
From the FDA Drug Label
In addition to the events reported during North American clinical trials with cefepime, the following adverse experiences have been reported during worldwide postmarketing experience. 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 Symptoms of overdose include encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, neuromuscular excitability and non-convulsive status epilepticus.
Cefepime toxicity can cause several adverse effects, including:
- Neurotoxicity: encephalopathy, myoclonus, seizures, and non-convulsive status epilepticus
- Renal impairment: increased risk of neurotoxicity
- Overdose symptoms: encephalopathy, myoclonus, seizures, neuromuscular excitability, and non-convulsive status epilepticus 2 2
From the Research
Cefepime Toxicity Overview
- Cefepime is a widely used antibiotic that can cause neurotoxicity, particularly in patients with renal dysfunction or those who receive excessive doses 3, 4.
- The symptoms of cefepime-induced neurotoxicity include altered mental status, myoclonus, seizures, and coma, which can be challenging to recognize in critically ill patients 3, 5.
Risk Factors for Cefepime Toxicity
- Renal dysfunction is a significant risk factor for cefepime neurotoxicity, as it can lead to elevated serum cefepime concentrations 3, 4.
- Excessive dosing, preexisting brain injury, and older age are also risk factors for cefepime-induced neurotoxicity 3, 6.
- Patients with chronic kidney disease are particularly susceptible to cefepime neurotoxicity, even when the dose is adjusted for renal function 4.
Clinical Manifestations of Cefepime Toxicity
- Altered mental status, myoclonus, and non-convulsive status epilepticus are common clinical manifestations of cefepime-induced neurotoxicity 3, 6, 7.
- The median latency period for developing cefepime-induced neurotoxicity is 4 days, and symptoms can resolve within 2-3 days after discontinuation of the drug or dose reduction 3, 7.
Diagnosis and Management of Cefepime Toxicity
- There are no clear diagnostic criteria or specific laboratory tests for cefepime-induced neurotoxicity, making diagnosis challenging 7.
- A high index of suspicion is required, and electroencephalography (EEG) can be useful in diagnosing non-convulsive status epilepticus 6.
- Discontinuation of cefepime or dose reduction can lead to improvement of symptoms in most patients, and antiepileptic drugs or hemodialysis may be necessary in some cases 3, 7.