Would you order cefepime (Cefepime) for a patient with end-stage renal disease (ESRD) on dialysis awaiting a CT (Computed Tomography) scan to rule out a periauricular abscess?

Cefepime Use in ESRD Patients with Suspected Periauricular Abscess

I would not routinely order cefepime for this patient without first considering safer alternatives, given the significant risk of neurotoxicity in ESRD patients on dialysis, even with appropriate renal dose adjustment.

Primary Concern: High Risk of Cefepime Neurotoxicity in ESRD

The evidence strongly indicates that cefepime carries substantial neurotoxicity risk in ESRD patients, even when doses are adjusted for renal function:

• Cefepime has a particularly low neurotoxicity threshold compared to other beta-lactams, with a relative pro-convulsive activity of 160 (compared to penicillin G = 100), making it the second most neurotoxic beta-lactam after cefazolin 1
• The incidence of cefepime-induced encephalopathy in ESRD patients is 7.5%, which is substantially higher than the 1.4% incidence in the general population 2
• Neurotoxicity occurs in ESRD patients regardless of daily dose, with cases reported even at 0.5g/day, demonstrating that standard renal dose adjustment may be inadequate 2
• Cefepime neurotoxicity can manifest as delirium, inability to tolerate oral intake, and non-convulsive status epilepticus, which can be life-threatening 3, 4

Specific Risk Factors to Assess

Before considering cefepime, evaluate for these high-risk features:

• Pre-existing CNS morbidity is significantly associated with increased risk of cefepime-induced encephalopathy in ESRD patients 2
• Elderly patients are at higher risk for both ototoxicity and neurotoxicity from beta-lactam antibiotics 1
• Patients with acute kidney injury superimposed on ESRD may have unpredictable drug accumulation 3

Recommended Alternative Approach

For a suspected periauricular abscess in an ESRD patient on dialysis, consider these safer alternatives:

First-Line Antibiotic Options:

• Meropenem has significantly lower neurotoxicity (relative pro-convulsive activity of 16 vs. cefepime's 160) and can be safely used in ESRD with appropriate dose adjustment 1
• Piperacillin-tazobactam is another reasonable alternative with lower neurotoxicity (piperacillin relative pro-convulsive activity of 11) 1
• For both agents, administer after dialysis to facilitate directly observed therapy and avoid premature drug removal 1

Dosing Strategy for ESRD:

• Reduce dosing frequency to 2-3 times weekly while maintaining the milligram dose at 12-15 mg/kg per dose to take advantage of concentration-dependent bactericidal effects 1
• Administer the dose post-dialysis 1

If Cefepime Must Be Used

Should clinical circumstances absolutely require cefepime (e.g., documented susceptibility pattern, allergy to alternatives):

Monitoring Requirements:

• Maintain neurological vigilance with frequent mental status assessments, as neurotoxicity can develop within 96 hours of therapy initiation 4
• Watch specifically for myoclonus, facial twitching, confusion, or altered consciousness 4
• Consider baseline and serial EEG monitoring if any neurological changes occur, as non-convulsive status epilepticus may not be clinically obvious 4
• Measure serum cefepime concentrations to avoid toxicity, particularly targeting trough concentrations below 22 mg/L for discontinuous infusions or steady-state concentrations below 35 mg/L for continuous infusions 1

Immediate Action Plan if Neurotoxicity Develops:

• Discontinue cefepime immediately 3
• Initiate emergent hemodialysis, which can shorten the time to return to non-toxic range by approximately 15 hours 5
• Administer benzodiazepines for seizure activity 4
• Obtain urgent EEG to assess for non-convulsive status epilepticus 4

Clinical Decision Algorithm

1. Obtain CT scan results first to confirm abscess presence and guide antibiotic selection
2. If abscess confirmed and antibiotics needed:
   • Assess for pre-existing CNS disease (stroke, dementia, seizure disorder)
   • If CNS disease present: Avoid cefepime entirely 2
   • If no CNS disease: Still prefer meropenem or piperacillin-tazobactam over cefepime 1
3. If cefepime is the only viable option (resistance patterns, allergies):
   • Use lowest effective dose (0.5-1g post-dialysis, 2-3 times weekly)
   • Implement intensive neurological monitoring
   • Have hemodialysis readily available for urgent drug removal 5

The key pitfall is assuming that renal dose adjustment alone provides adequate safety in ESRD patients—the evidence clearly demonstrates it does not 3, 2, 4.