What is the recommended dose of cefepime (Fourth-generation cephalosporin) for treating nosocomial infections in patients with normal and impaired renal function?

Cefepime Dosing for Nosocomial Infections

For nosocomial infections in critically ill patients with normal renal function, administer cefepime 2 g intravenously every 8 hours, which provides optimal coverage against multidrug-resistant pathogens including Pseudomonas aeruginosa. 1

Standard Dosing for Normal Renal Function

For critically ill patients with healthcare-associated infections and normal renal function (CrCl >60 mL/min), the recommended dose is 2 g IV every 8 hours. 1 This higher dosing frequency is critical because:

• Standard twice-daily dosing fails to achieve adequate pharmacodynamic targets in 37-44% of ICU patients due to increased drug clearance and expanded volume of distribution from fluid resuscitation 2
• The 8-hour interval ensures drug concentrations remain above the MIC for ≥70% of the dosing interval, which is essential for optimal bacterial killing 3, 4
• For infections with Pseudomonas aeruginosa or other pathogens with MICs at the upper susceptibility limit (8 mg/L), only 45-65% of patients achieve adequate coverage with standard dosing 3

Administration Method

Administer each dose as an intravenous infusion over approximately 30 minutes. 5 For severe infections with high-MIC organisms (≥4 mg/L), consider extended infusions (4 hours) or continuous infusion to optimize time above MIC, particularly for Pseudomonas infections 1, 2, 6

Dosing Adjustments for Renal Impairment

Cefepime requires careful dose adjustment based on creatinine clearance to prevent drug accumulation and neurotoxicity 5, 3:

CrCl 30-60 mL/min

• 2 g every 12 hours for severe infections 5
• 1 g every 24 hours for moderate infections 5

CrCl 11-29 mL/min

• 2 g every 24 hours for severe infections 5
• 1 g every 24 hours for moderate infections 5

CrCl <11 mL/min

• 1 g every 24 hours for severe infections 5
• 500 mg every 24 hours for moderate infections 5

Hemodialysis

• Loading dose: 1 g on Day 1 5
• Maintenance: 500 mg every 24 hours (or 1 g every 24 hours for febrile neutropenia) 5
• Administer after dialysis sessions, as approximately 68% of cefepime is removed during a 3-hour dialysis period 5

Continuous Renal Replacement Therapy (CRRT)

• Loading dose: 2 g, followed by 1.5-1.75 g every 8 hours for Gram-negative infections with KDIGO-recommended effluent rates 7
• Standard clinical resources significantly underdose patients on CRRT; higher doses are required to achieve therapeutic targets 7

Critical Safety Considerations

Neurotoxicity Monitoring

Monitor closely for neurotoxicity, especially in patients with renal impairment, as cefepime has high pro-convulsive activity. 6, 3 Warning signs include:

• Confusion and altered mental status 3
• Myoclonus and muscle jerks 3
• Non-convulsive seizures 3
• Encephalopathy 2

Two critical pitfalls: 3

1. Neurotoxicity can occur even with "appropriate" dose adjustments in patients with CrCl <30 mL/min, with trough concentrations reaching 20-30 mg/L
2. Symptoms may be mistaken for ICU delirium or septic encephalopathy; consider therapeutic drug monitoring if neurological symptoms develop

Therapeutic Drug Monitoring

Consider therapeutic drug monitoring in critically ill patients, particularly those with: 2, 3

• Fluctuating renal function
• Infections with high-MIC pathogens (≥8 mg/L)
• Any neurological symptoms
• Target trough concentrations should not exceed 8× MIC due to neurotoxicity risk 2

Specific Nosocomial Infection Types

Nosocomial Pneumonia

• 2 g IV every 8 hours for moderate to severe pneumonia 5, 8
• Duration: typically 10 days 5
• For Pseudomonas aeruginosa specifically, use 2 g every 8 hours 1, 5

Healthcare-Associated Intra-Abdominal Infections

• 2 g IV every 8 hours + metronidazole 500 mg every 6 hours 1, 5
• Duration: 7-10 days 5
• This combination provides coverage for anaerobes, which cefepime does not adequately cover 1

Complicated Urinary Tract Infections

• 2 g IV every 12 hours for severe infections 5
• 0.5-1 g IV every 12 hours for mild to moderate infections 5
• Duration: 7-10 days 5

Febrile Neutropenia

• 2 g IV every 8 hours 5
• Continue for 7 days or until resolution of neutropenia 5

Key Clinical Pearls

• Cefepime plasma concentrations vary 2-3 fold at peak and up to 40-fold at trough between individuals, emphasizing the importance of appropriate dosing 3
• The drug maintains stability against many plasmid- and chromosome-mediated beta-lactamases and is a poor inducer of AmpC beta-lactamases, making it effective against Enterobacter species resistant to third-generation cephalosporins 8
• For combination therapy with aminoglycosides (e.g., mucoid Pseudomonas), cefepime enhances bacterial killing even when monotherapy fails 4
• CNS penetration is variable (4-34%) but adequate for most nosocomial pathogens in patients with external ventricular drains 9