Cefepime-Induced Neurotoxicity
Cefepime is the most likely cause of this patient's agitation, confusion, and myoclonus, and should be discontinued immediately. 1, 2, 3
Clinical Reasoning
This patient presents with the classic triad of cefepime neurotoxicity occurring on day 4 of therapy:
- Altered mental status (agitation and confusion) 3, 4
- Myoclonus 3, 4
- Renal impairment (creatinine 3.2, eGFR 41) 1, 3
The timing is characteristic—median onset is 4 days after starting cefepime, with a range of 1-10 days. 3, 4, 5 This patient developed symptoms exactly at the median timepoint. 3
Why Cefepime Over Other Diagnoses
Renal dysfunction is the primary risk factor for cefepime neurotoxicity, present in 80% of cases, and this patient has significant renal impairment. 3, 4 Critically, neurotoxicity occurs in 26% of patients despite appropriate renal dose adjustment, so proper dosing does not exclude this diagnosis. 1, 3, 4
Cefepime has a relative pro-convulsive activity of 160 compared to penicillin G at 100, making it one of the most neurotoxic beta-lactam antibiotics through GABA antagonism. 1 The drug crosses the blood-brain barrier and causes concentration-dependent neurotoxicity. 3
Against uremic encephalopathy: While the patient has renal impairment (BUN 40, Cr 3.2), uremic encephalopathy typically develops more gradually and would not explain the acute onset on day 4 with improving clinical status otherwise (fever resolved, oxygen requirements improved). 3, 4
Against baclofen withdrawal: Baclofen withdrawal typically presents with hallucinations, hyperthermia, and autonomic instability rather than isolated myoclonus and confusion. The patient is intubated and sedated in the ICU, making it unlikely that baclofen was abruptly discontinued. 6
Against acute thrombotic stroke: The clinical improvement in other parameters (fever resolution, improved oxygenation) and the presence of myoclonus—which is characteristic of metabolic/toxic encephalopathy rather than stroke—make this unlikely. 3, 4
Supporting Evidence
Up to 15% of ICU patients treated with cefepime experience neurotoxic effects, with the most common symptoms being: 3
- Reduced consciousness (47%)
- Myoclonus (42%)
- Confusion (42%)
EEG abnormalities occur in 100% of tested patients, including triphasic waves (40%), non-convulsive status epilepticus (25%), and focal sharp waves (39%). 3, 4
The FDA drug label explicitly states that overdosage symptoms include "encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, and neuromuscular excitability" particularly in patients with renal impairment. 2
Immediate Management
Discontinue cefepime immediately upon suspicion of neurotoxicity. 1, 7 This is the most critical intervention.
Consider hemodialysis if symptoms are severe or not improving, as it aids in cefepime removal (peritoneal dialysis is not effective). 2, 3 In reported cases, symptom resolution occurred a median of 2 days after intervention. 3
Administer benzodiazepines if seizure activity is present. 7
Switch to alternative antibiotics with lower neurotoxicity risk: 7, 8
- Cefotaxime or ceftriaxone (hepatic and renal excretion, lower neurotoxicity)
- Meropenem (same spectrum, 16% relative pro-convulsive activity versus cefepime's 160%)
- Cefoxitin (lowest seizure risk at 1.8% if cephalosporin required)
Critical Pitfall
Do not wait for EEG confirmation before discontinuing cefepime. While EEG abnormalities are universal in tested patients, the diagnosis is clinical and delays in recognition are common because altered mental status has multiple potential causes in critically ill patients. 3, 9 The median delay from drug initiation to symptom onset is 4 days, and 89% of patients improve with intervention. 3