Cefepime Can Cause Neurotoxicity and Mental Status Changes
Yes, cefepime can significantly affect mental status, causing neurotoxicity that may manifest as encephalopathy, confusion, altered consciousness, myoclonus, and even nonconvulsive status epilepticus. 1, 2
Mechanism and Risk Factors
- Cefepime has high pro-convulsive activity, making it one of the most neurotoxic beta-lactam antibiotics with a relative activity of 160% compared to penicillin G 3
- Renal impairment is the primary risk factor for cefepime-induced neurotoxicity due to drug accumulation, but neurotoxicity can occur even when dosing is appropriately adjusted for renal function 1
- Neurotoxicity can occur in patients with normal renal function, though it's less common 4
- The FDA drug label specifically lists "encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), aphasia, myoclonus, seizures, and nonconvulsive status epilepticus" as postmarketing adverse reactions 5
Clinical Manifestations
- Altered mental status is present in all cases of cefepime neurotoxicity, with the most common symptoms being 2:
- Reduced consciousness (47% of cases)
- Myoclonus (42% of cases)
- Confusion (42% of cases)
- Electroencephalography (EEG) abnormalities are present in all patients with suspected cefepime neurotoxicity who undergo testing, including 2:
- Non-convulsive status epilepticus (25%)
- Myoclonic status epilepticus (7%)
- Triphasic waves (40%)
- Focal sharp waves (39%)
Time Course and Diagnosis
- Symptoms typically begin around 4 days after starting cefepime therapy (median), but can occur from 1-10 days after initiation 2, 6
- In rare cases, neurotoxicity can develop after prolonged therapy (e.g., 4 weeks) 6
- Diagnosis is often delayed because symptoms can mimic other conditions common in critically ill patients, including stroke 6
- Cefepime trough concentrations above 22 mg/L or steady-state concentrations above 35 mg/L are associated with neurotoxicity in 50% of patients 1
Management
- Immediate discontinuation of cefepime is the primary intervention when neurotoxicity is suspected 1
- Symptoms typically resolve within a median of 2 days after cefepime discontinuation 2
- Some cases may require additional interventions such as antiepileptic drugs or hemodialysis 2
- Recovery occurs in approximately 89% of patients 2
Prevention
- Appropriate dosing based on renal function is essential, as 48% of reported cases involved overdosing per FDA guidelines 2
- Regular monitoring of mental status in all patients receiving cefepime, not just those with renal dysfunction 7
- Consider alternative antibiotics in high-risk patients, particularly those with renal dysfunction or history of seizures 3
Clinical Pitfalls
- Cefepime neurotoxicity can be mistaken for other conditions such as stroke, delirium, or septic encephalopathy 6
- 26% of neurotoxicity cases occur despite appropriate dosing based on renal function 2
- Patients with normal renal function can still develop neurotoxicity, though this is less common 4
- EEG is essential for diagnosis, particularly when nonconvulsive status epilepticus is suspected 2, 6