Can cefepime cause confusion?

Cefepime Can Cause Confusion and Encephalopathy

Yes, cefepime frequently causes confusion and other neurotoxic effects, occurring in up to 15% of ICU patients, with altered mental status being the most common manifestation. 1

Clinical Manifestations of Cefepime Neurotoxicity

The neurological symptoms present in a characteristic pattern:

• Confusion and altered mental status occur in 100% of affected patients, making it the hallmark feature 1
• Reduced consciousness develops in 47% of cases 1
• Myoclonus (involuntary muscle jerking) appears in 33-42% of patients 1, 2
• Confusion with temporospatial disorientation affects 96% of patients 2
• Seizures occur in 13% of cases 2
• Other manifestations include encephalopathy, aphasia, stupor, and coma 3, 1

Mechanism and Why It Occurs

Cefepime crosses the blood-brain barrier and exhibits concentration-dependent GABA antagonism, leading to neurotoxic effects 1. Cefepime has extremely high pro-convulsive activity (160 compared to penicillin G at 100), making it one of the most neurotoxic beta-lactam antibiotics 4.

Critical Risk Factors

Renal Dysfunction (Most Important)

• Renal impairment is present in 80% of neurotoxicity cases 1
• Drug accumulation occurs even with appropriate dose adjustments 4
• 26% of patients develop neurotoxicity despite receiving appropriately adjusted doses for renal function 4, 1
• Cefepime trough concentrations above 22 mg/L or steady-state concentrations above 35 mg/L are associated with neurotoxicity in 50% of patients 4

Other Risk Factors

• Advanced age (median age 69 years in affected patients) 1
• Critical illness requiring ICU care (81% of cases) 1
• Preexisting brain injury 1
• Depression and cancer may represent occult risk factors due to blood-brain barrier dysfunction 5

Diagnostic Features

EEG Abnormalities (Highly Characteristic)

• All patients (100%) who underwent EEG testing showed abnormalities 1
• Triphasic waves appear in 40% of cases 1, 6
• Non-convulsive status epilepticus occurs in 25% 1
• Generalized periodic discharges and generalized rhythmic delta activity with admixed sharps 7
• The presence of diffuse rhythmic non-reactive triphasic sharp waves is particularly characteristic 6

Laboratory Findings

• Median cefepime serum concentration in affected patients: 45 mg/L 1
• Median CSF concentration: 13 mg/L 1

Clinical Course and Timeline

• Median delay from starting cefepime to symptom onset: 4 days 1
• Symptoms can develop as late as 11 days after initiation 5
• Median time to resolution after intervention: 2 days 1
• Complete resolution typically occurs within 24-48 hours after drug discontinuation 6

Common Diagnostic Pitfall

The risk of delayed diagnosis is significant—the median interval between symptom onset and diagnosis is 5 days 2. This delay occurs because:

• Confusion and altered mental status are common in ICU patients from multiple causes 1
• Clinicians often lack awareness of this adverse effect 2
• Psychiatric symptoms can be confused with depression or delirium from other causes 5

Immediate Management

Primary Intervention

• Immediately discontinue cefepime upon suspicion of neurotoxicity 4
• Symptom improvement occurs in 89% of patients with drug discontinuation 1
• 87% of patients survive to hospital discharge 1

Additional Interventions When Needed

• Administer benzodiazepines for seizure activity if present 8
• Consider antiepileptic drugs (lorazepam, topiramate, levetiracetam) 7
• Hemodialysis may be required in severe cases, particularly with renal impairment 1
• In severe renal injury, cefepime clearance is prolonged and neurotoxicity may persist longer 4
• Monitor and correct electrolyte imbalances that may exacerbate neurological symptoms 8

What NOT to Do

• Avoid corticosteroids—cefepime neurotoxicity is not immune-mediated inflammation but rather due to drug accumulation 4

Alternative Antibiotic Selection

When cefepime must be avoided:

• Switch to cefotaxime or ceftriaxone, which have both hepatic and renal excretion pathways and lower neurotoxicity risk 8
• Meropenem is an excellent alternative with the same antimicrobial spectrum but significantly lower neurotoxicity (16% relative pro-convulsive activity compared to ceftazidime) 8
• Cefoxitin has the lowest seizure risk among beta-lactams (1.8% compared to penicillin G) if a cephalosporin is required 8

When Cefepime Must Be Used in ESRD

If no alternative exists:

• Use intermittent dosing of 1-2g three times weekly, preferably after hemodialysis 4
• Always administer after hemodialysis, never before 4

Key Monitoring Recommendation

Advise patients and caregivers to immediately report any neurological signs including confusion, hallucinations, stupor, myoclonus, or seizures for immediate treatment, dosage adjustment, or discontinuation 3.