Management of Cefepime-Induced Myoclonus
The most effective management of cefepime-induced myoclonus is immediate discontinuation of cefepime, with consideration of hemodialysis in severe cases or when symptoms persist despite drug cessation.
Pathophysiology and Clinical Presentation
Cefepime neurotoxicity occurs due to the drug's ability to cross the blood-brain barrier and antagonize GABA-A receptors 1. This neurotoxicity typically manifests as:
- Myoclonus (present in 42% of cases)
- Altered mental status/encephalopathy (present in nearly all cases)
- Confusion (42% of cases)
- Seizures, including nonconvulsive status epilepticus
- Aphasia
- Coma in severe cases
Risk Factors
The French Society of Pharmacology and Therapeutics identifies several key risk factors 2:
- Renal dysfunction (present in 80% of cases) 1
- Advanced age
- Excessive dosing (48% of cases received doses higher than FDA recommendations) 1
- Preexisting brain injury
- Elevated serum cefepime concentrations
It's important to note that cefepime neurotoxicity can occur even with appropriate dosing (26% of cases) 1.
Management Algorithm
Step 1: Recognition and Diagnosis
- Suspect cefepime neurotoxicity in any patient on cefepime who develops:
- New-onset myoclonus
- Unexplained altered mental status
- Seizure activity
- Obtain EEG (abnormalities present in 100% of tested cases) 1
- Look for triphasic waves (40%)
- Focal sharp waves (39%)
- Nonconvulsive status epilepticus (25%)
- Check cefepime levels if available (median serum level in toxicity: 45 mg/L) 1
- Assess renal function
Step 2: Immediate Management
- Discontinue cefepime immediately 3
- Switch to alternative antimicrobial therapy based on infection type and susceptibility
- Consider hemodialysis in severe cases, as it effectively removes cefepime from the body 3
Step 3: Symptomatic Management
- For persistent myoclonus or seizures:
- Administer antiepileptic drugs 1
- Options include sodium valproate, levetiracetam, phenytoin, benzodiazepines, propofol, or barbiturates 2
- Propofol is particularly effective for post-anoxic myoclonus 2
- Clonazepam, sodium valproate, and levetiracetam are antimyoclonic drugs that may be effective 2
- Note that phenytoin is often ineffective for myoclonus 2
Step 4: Monitoring and Follow-up
- Monitor neurological status closely until resolution
- Expect improvement within approximately 2 days after intervention 1
- Consider repeat EEG to document improvement
Special Considerations
Dosing Adjustments
When continuing other beta-lactam antibiotics, the French Society of Pharmacology and Therapeutics recommends 2:
- Avoid plasma free concentrations above 8 times the MIC
- For cefepime specifically, trough concentrations above 22 mg/L (with discontinuous infusions) or steady-state concentrations above 35 mg/L (with continuous infusion) are associated with neurotoxicity in 50% of patients
Prevention Strategies
- Properly adjust cefepime dosing based on renal function
- Monitor renal function regularly during therapy
- Consider alternative antibiotics in high-risk patients
- Be aware that cefepime has higher pro-convulsive activity (160 relative to penicillin G at 100) compared to many other beta-lactams 2
Prognosis
With appropriate management, the prognosis is generally favorable:
- Symptom improvement occurs in 89% of patients
- 87% survive to hospital discharge
- Median time to symptom resolution is 2 days after intervention 1
Common Pitfalls to Avoid
- Misdiagnosing cefepime neurotoxicity as stroke, especially when focal neurological deficits are present 4
- Continuing cefepime despite neurological symptoms
- Failing to consider cefepime toxicity in patients with appropriate dosing
- Overlooking the possibility of cefepime toxicity in patients with normal renal function
- Delaying EEG in patients with unexplained neurological symptoms
Remember that cefepime neurotoxicity is likely underreported and should be suspected in any patient receiving cefepime who develops unexplained neurological manifestations 3.