Can cefepime cause delirium?

Cefepime-Induced Delirium

Yes, cefepime can definitely cause delirium, particularly in patients with renal impairment, and this neurotoxicity may occur even with appropriate dosing. 1, 2

Mechanism and Risk Factors

Cefepime has significant neurotoxic potential due to several factors:

• High pro-convulsive activity: Cefepime has a relative pro-convulsive activity of 160 compared to penicillin G (100), making it one of the more neurotoxic beta-lactam antibiotics 1
• Blood-brain barrier penetration: Cefepime crosses the blood-brain barrier and exhibits concentration-dependent GABA antagonism 3
• Renal clearance: Cefepime is primarily eliminated by the kidneys, causing accumulation in patients with impaired renal function 2

Primary Risk Factors:

• Renal impairment: The most significant risk factor 1, 2, 4
• Excessive dosing: 48% of neurotoxicity cases involve doses exceeding FDA recommendations 3
• Advanced age: Elderly patients are at higher risk due to decreased renal function 2
• Pre-existing brain injury or neurological conditions 3

Clinical Presentation

Cefepime neurotoxicity typically manifests as:

• Altered mental status/delirium: Confusion, disorientation, reduced consciousness (47% of cases) 3
• Myoclonus: Involuntary muscle jerking (42% of cases) 3
• Encephalopathy: Disturbance of consciousness including confusion, hallucinations, stupor, and coma 2
• Seizures: Including non-convulsive status epilepticus 2, 3
• Aphasia: Global aphasia has been reported in some cases 4

Timing and Diagnosis

• Onset: Typically occurs 4-5 days after starting cefepime (range: 1-10 days) 4, 3
• EEG findings: Abnormalities in 100% of tested patients, including triphasic waves (40%), focal sharp waves (39%), and non-convulsive status epilepticus (25%) 3
• Laboratory: Elevated cefepime levels in serum (median 45 mg/L) and CSF (median 13 mg/L) 3
• Diagnostic challenge: Symptoms often mimic other conditions common in critically ill patients 3

Management

When cefepime-induced delirium is suspected:

1. Discontinue cefepime immediately: This is the most important intervention 3, 5
2. Consider hemodialysis: Recommended in cases of overdose or severe symptoms, as peritoneal dialysis is ineffective 2
3. Antiepileptic medications: May be necessary if seizures are present 3
4. Monitor for improvement: Symptoms typically resolve within 2 days after intervention (range: 1-7 days) 3

Prevention

• Appropriate renal dosing: Adjust dose in patients with creatinine clearance ≤60 mL/min 2
• Regular monitoring: Assess mental status and neurological function in all patients receiving cefepime, particularly those with risk factors 1
• Consider alternatives: In patients with significant renal impairment or history of neurological disorders, consider beta-lactams with lower neurotoxicity potential 1

Important Caveats

• Neurotoxicity despite appropriate dosing: 26% of cases occur despite FDA-recommended dosing adjustments 3
• Underrecognition: Cefepime neurotoxicity is likely underreported and insufficiently recognized 4
• Mortality risk: While most patients recover with drug discontinuation (89%), some cases have been associated with mortality 4, 3
• Differential diagnosis: Consider other causes of delirium in hospitalized patients, including other medications, metabolic disturbances, and infections 1

Conclusion

Clinicians should maintain a high index of suspicion for cefepime-induced delirium, particularly in patients with renal impairment. Prompt recognition and discontinuation of the drug are essential for resolution of symptoms and prevention of potential complications.