What is the recommended dose and frequency of cefepime (Cefepime) for empiric therapy in patients with varying degrees of renal function, such as normal renal function or impaired renal function?

Cefepime Dosing and Frequency for Empiric Therapy

Standard Dosing for Normal Renal Function

For empiric therapy in patients with normal renal function, cefepime should be administered at 2 g intravenously every 8 hours, particularly for critically ill patients, severe infections, or suspected multidrug-resistant pathogens including Pseudomonas aeruginosa. 1, 2

Dosing by Clinical Scenario

Severe infections and critically ill patients:

• 2 g IV every 8 hours is the recommended dose for hospital-acquired pneumonia, healthcare-associated infections, and sepsis in patients with preserved renal function 1, 2
• This higher dose accounts for increased clearance and volume of distribution in critically ill patients, where 37-44% fail to achieve therapeutic targets with standard dosing 2
• For Pseudomonas aeruginosa specifically, 2 g every 8 hours provides optimal coverage 2

Moderate infections:

• 1-2 g IV every 8-12 hours may be appropriate for less severe infections, though the higher dose and more frequent interval are preferred for empiric therapy when pathogen susceptibility is unknown 3, 4

Pediatric dosing:

• 50 mg/kg every 8-12 hours (maximum 2 g per dose) for children ≥2 months of age 2, 5
• The 8-hour interval is preferred for serious infections 5, 6

Dosing Adjustments for Renal Impairment

Cefepime requires dose adjustment in renal dysfunction since approximately 85% is renally excreted as unchanged drug. 3

Renal Dosing Algorithm

Creatinine clearance >60 mL/min:

• No adjustment needed; use standard dosing of 2 g every 8 hours 3

Creatinine clearance 30-60 mL/min:

• Reduce frequency to every 12 hours while maintaining dose 3

Creatinine clearance 11-29 mL/min:

• Reduce frequency to every 24 hours 3

Creatinine clearance ≤10 mL/min:

• Further dose reduction required; consult package labeling for specific recommendations 3

Hemodialysis patients:

• Average half-life extends to 13.5 hours; administer supplemental doses after dialysis sessions 3

Continuous peritoneal dialysis:

• Half-life extends to 19 hours; adjust dosing interval accordingly 3

Administration Strategies for Optimization

Extended or continuous infusions should be strongly considered for severe infections, particularly when treating organisms with high MICs (≥4 mg/L) or Pseudomonas infections. 2, 7

Infusion Strategy Selection

Standard 30-minute infusion:

• Appropriate for most infections with susceptible organisms (MIC ≤2 mg/L) 3

Extended infusion (3-4 hours):

• Recommended for high-MIC pathogens (≥4 mg/L) to optimize time above MIC 2
• Improves pharmacokinetic/pharmacodynamic target attainment in critically ill patients 2

Continuous infusion:

• May provide additional benefit in sepsis and critically ill patients by maintaining concentrations above MIC throughout the dosing interval 2
• A loading dose should be given as rapid bolus initially, followed by continuous infusion 2

Critical Monitoring and Safety Considerations

Therapeutic drug monitoring should be considered in critically ill patients, especially those with fluctuating renal function, to balance efficacy against neurotoxicity risk. 2, 8

Neurotoxicity Risk Management

Key monitoring parameters:

• Monitor for confusion, encephalopathy, myoclonus, and seizures, particularly in renal impairment 2, 7
• Cefepime has relatively high pro-convulsive activity (160 on relative scale where penicillin G = 100) 7
• Risk increases when trough concentrations exceed 8× MIC 2
• Neurotoxicity probability should not exceed 20% when selecting dosing regimens 8

Renal function monitoring:

• Assess creatinine clearance at baseline and monitor throughout therapy, as clearance decreases proportionally with renal function 3
• Elderly patients (≥65 years) require particular attention to renal function and may need dose adjustment if creatinine clearance ≤60 mL/min 3

Common Pitfalls to Avoid

Underdosing in critically ill patients: Standard doses (1 g every 12 hours) are frequently inadequate in ICU patients due to augmented renal clearance and increased volume of distribution 2

Failure to adjust for renal impairment: Accumulation occurs rapidly in renal dysfunction, increasing neurotoxicity risk without dose reduction 3, 8

Inadequate coverage for high-MIC organisms: Doses exceeding 4 g daily may be required for Pseudomonas with elevated MICs; consider extended infusions rather than just increasing dose 2

Administering before dialysis: For hemodialysis patients, doses should be given after dialysis to prevent premature drug removal 3