What is the recommended dosing for Cefepime (Cefepime) in adults with varying degrees of renal function?

Cefepime Dosing in Adults with Varying Renal Function

For adults with normal renal function (CrCl >60 mL/min), use 1-2g IV every 8-12 hours depending on infection severity, with higher doses (2g every 8 hours) recommended for critically ill patients, severe pneumonia, and infections with high-MIC organisms like Pseudomonas aeruginosa; dose adjustments are mandatory for renal impairment following a structured algorithm based on creatinine clearance. 1

Standard Dosing for Normal Renal Function (CrCl >60 mL/min)

Infection-Specific Dosing

• Moderate to severe pneumonia: 1-2g IV every 8-12 hours for 10 days 1
• Severe pneumonia or Pseudomonas aeruginosa: 2g IV every 8 hours 2, 1
• Complicated intra-abdominal infections (with metronidazole): 2g IV every 8-12 hours for 7-10 days 1
• Severe urinary tract infections/pyelonephritis: 2g IV every 12 hours for 10 days 1
• Mild to moderate UTI: 0.5-1g IV every 12 hours for 7-10 days 1
• Uncomplicated skin/soft tissue infections: 2g IV every 12 hours for 10 days 1
• Febrile neutropenia: 2g IV every 8 hours for 7 days or until neutropenia resolves 1

Critical Care Considerations

Critically ill patients with preserved renal function require higher initial doses than standard recommendations due to increased clearance and volume of distribution. 2, 3

• Initial dosing in ICU patients: Consider 2g every 8 hours, particularly for sepsis or infections with high-MIC pathogens 2, 3
• Studies demonstrate that 37-44% of ICU patients fail to achieve therapeutic targets with standard dosing 2
• Doses exceeding 4g daily may be required for Pseudomonas infections with elevated MICs 2

Renal Impairment Dosing Algorithm

Dose adjustments are based on creatinine clearance, with the initial dose remaining the same as normal renal function but subsequent doses reduced. 1, 4

CrCl 30-60 mL/min

• All indications: Reduce frequency to every 24 hours for lower doses (500mg-1g) or every 12 hours for 2g doses 1
• Example: 2g every 12 hours (instead of every 8 hours) 1

CrCl 11-29 mL/min

• 500mg dose: 500mg every 24 hours 1
• 1g dose: 500mg every 24 hours 1
• 2g dose: 1g every 24 hours 1

CrCl <11 mL/min

• 500mg dose: 250mg every 24 hours 1
• 1g dose: 250mg every 24 hours 1
• 2g dose: 500mg every 24 hours 1

Hemodialysis

• Loading dose: 1g on Day 1 1
• Maintenance: 500mg every 24 hours for most infections, or 1g every 24 hours for febrile neutropenia 1
• Timing: Administer after dialysis completion, as approximately 68% is removed during a 3-hour session 1, 4
• Elimination half-life decreases from 13.5 hours pre-dialysis to 2.3 hours during dialysis 4

Continuous Ambulatory Peritoneal Dialysis (CAPD)

• Administer recommended doses every 48 hours 1

Continuous Renal Replacement Therapy (CRRT)

• Optimal dosing: 2g loading dose followed by 1.5-1.75g every 8 hours for Gram-negative infections 5
• Standard clinical resources significantly underdose cefepime in CRRT patients 5
• Dosing should account for effluent rates, as cefepime is readily removed by CRRT 5

Administration Strategies

Prolonged/Continuous Infusions

For infections with high-MIC organisms (particularly Pseudomonas), prolonged or continuous infusions improve pharmacokinetic/pharmacodynamic target attainment. 2, 3, 6

• Standard administration: Infuse over 30 minutes 1
• Extended infusion: Consider for severe infections or MIC ≥4 mg/L 2, 6
• This strategy increases the percentage of time free drug concentrations exceed the MIC 2

Monitoring and Safety

Therapeutic Drug Monitoring

• Recommended for: Critically ill patients, fluctuating renal function, suspected treatment failure 3
• Target: Free drug concentrations exceeding 4× MIC for 70% of dosing interval 5
• Risk-benefit balance decreases when trough concentrations exceed 8× MIC due to neurotoxicity risk 2

Neurotoxicity Risk

Cefepime has relatively high pro-convulsive activity and neurotoxicity risk increases with renal dysfunction and higher cumulative doses. 6, 7

• Monitor for confusion, encephalopathy, myoclonus, and seizures 3, 7
• Neurotoxicity occurs in 4-10% of patients overall, but up to 16% in severe renal dysfunction with higher doses (≥4g in first 48 hours) 7
• Most common presentation: Altered mental status (92% of cases) 7
• Critical threshold: Patients with severe renal dysfunction receiving ≥4g in first 48 hours have significantly elevated risk 7

Common Pitfalls

• Failure to adjust for renal function: Cefepime elimination half-life increases from 2.3 hours (normal) to 13.5 hours (severe impairment), necessitating dose reduction 4
• Underdosing in ICU patients: Standard doses often fail to achieve targets in critically ill patients with augmented renal clearance 2
• Inadequate dosing in CRRT: Clinical resources consistently recommend insufficient doses for patients on CRRT 5
• Missing neurotoxicity: Maintain high suspicion in renally impaired patients, especially with altered mental status 7