What is the recommended IV (intravenous) cefepime dose for patients with End-Stage Renal Disease (ESRD)?

IV Cefepime Dosing in ESRD

For patients with end-stage renal disease (ESRD) on hemodialysis, administer cefepime 1 g on Day 1, followed by 500 mg every 24 hours for most infections, or 1 g every 24 hours for febrile neutropenia, with doses given after hemodialysis sessions. 1

Dosing Based on Renal Function

The FDA-approved dosing for cefepime in ESRD requires significant adjustment from standard dosing due to predominantly renal elimination 1, 2:

For Hemodialysis Patients:

• Initial dose: 1 g on Day 1 1
• Maintenance dose: 500 mg every 24 hours for most infections 1
• Febrile neutropenia: 1 g every 24 hours 1
• Timing: Administer after hemodialysis on dialysis days to avoid premature drug removal 1

For Continuous Ambulatory Peritoneal Dialysis (CAPD):

• Dosing interval extends to every 48 hours 1
• Doses range from 500 mg to 2 g every 48 hours depending on infection severity 1

For Creatinine Clearance <11 mL/min (not on dialysis):

• 250 mg to 1 g every 24 hours depending on infection severity 1

Pharmacokinetic Rationale

Cefepime is eliminated primarily by glomerular filtration, with renal clearance accounting for >80% of drug elimination 2, 3. In ESRD patients:

• Hemodialysis removes approximately 68% of cefepime during a 3-hour dialysis session 1
• Dialysis clearance ranges from 69.9 to 94.6 mL/(min × 1.73 m²) 3
• Mean residence time increases dramatically from 2.4 hours in normal renal function to 31.6 hours in ESRD 3
• Area under the curve increases three-fold even with moderate renal impairment 3

Critical Safety Considerations

Neurotoxicity Risk in ESRD

Even with appropriate dose adjustment, ESRD patients remain at significant risk for cefepime-induced encephalopathy (CFPMIE), with an incidence of 7.5% in this population. 4

Key safety points:

• Pre-existing CNS disease significantly increases CFPMIE risk in ESRD patients 4
• CFPMIE can occur even with doses as low as 0.5 g/day in ESRD patients 4
• Symptoms include confusion, muscle jerks, non-convulsive status epilepticus, and altered consciousness 5, 6
• Advanced age combined with uremic encephalopathy increases susceptibility to neurotoxicity 6

Monitoring and Management

For ESRD patients receiving cefepime 5, 6:

• Monitor neurological status closely, especially in elderly patients or those with pre-existing CNS disease 4, 6
• Consider plasma level monitoring when available, particularly if neurological symptoms develop 5, 6
• Target trough concentrations should remain below 20 mg/L to avoid toxicity 5
• If neurotoxicity occurs, discontinue cefepime immediately and consider urgent hemodialysis to enhance drug clearance 6

Alternative Considerations

In very elderly ESRD patients or those with CNS comorbidities, consider alternatives with dual hepatic and renal elimination 6:

• Cefotaxime or ceftriaxone (mixed hepatic/renal excretion) 6
• Meropenem (similar spectrum, lower neurotoxicity risk) 6

Pharmacodynamic Targets

For optimal efficacy, cefepime concentrations should remain above the MIC for ≥50% of the dosing interval (T>MIC ≥50%) 5:

• Standard ESRD dosing provides adequate coverage for pathogens with MIC ≤4 mg/L 5
• Coverage may be inadequate for organisms with MIC ≥8 mg/L (upper limit of susceptibility) 5
• For Pseudomonas aeruginosa or other resistant organisms, consider therapeutic drug monitoring 5

Practical Algorithm

1. Confirm ESRD status and dialysis schedule 1
2. Assess for CNS risk factors: advanced age, pre-existing neurological disease, uremic encephalopathy 4, 6
3. Initiate dosing: 1 g Day 1, then 500 mg every 24 hours (or 1 g every 24 hours for febrile neutropenia) 1
4. Time doses after hemodialysis on dialysis days 1
5. Monitor neurological status daily, especially in first week 4, 6
6. If confusion or neurological symptoms develop: discontinue cefepime, consider urgent dialysis, and switch to alternative antibiotic 6