What is the recommended dosing regimen for cefepime in treating Pseudomonas infections, especially in patients with impaired renal function?

Cefepime Dosing for Pseudomonas Infections

For Pseudomonas aeruginosa infections, cefepime should be dosed at 2g IV every 8 hours to ensure optimal efficacy, with dosage adjustments required for patients with renal impairment. 1, 2

Standard Dosing Recommendations

Normal Renal Function (CrCl >60 mL/min)

• Adults: 2g IV every 8 hours 1, 3
• Pediatric patients: 50 mg/kg IV every 8 hours (not to exceed adult dose) 1, 3

Renal Impairment Dosage Adjustments 1

• CrCl 30-60 mL/min: 2g IV every 12 hours
• CrCl 11-29 mL/min: 2g IV every 24 hours
• CrCl <11 mL/min: 1g IV every 24 hours
• Hemodialysis: 1g on day 1, then 500 mg every 24 hours (administer after hemodialysis on dialysis days)
• CAPD: 2g every 48 hours

Pharmacodynamic Considerations

The efficacy of cefepime against Pseudomonas aeruginosa is highly dependent on maintaining adequate time above MIC:

• Clinical studies have demonstrated that maintaining free cefepime concentrations above the MIC for >60% of the dosing interval is critical for microbiological success 4
• Patients with fT>MIC ≤60% experienced 77.8% treatment failure, compared to only 36.2% failure when fT>MIC was >60% 4
• The standard 2g every 12 hours regimen may be inadequate for Pseudomonas infections, particularly with higher MICs 5

Administration Methods

Several administration methods can be considered to optimize pharmacodynamics:

1. Standard intermittent infusion: Administer over approximately 30 minutes 1
2. Extended infusion: Administering over 3-6 hours may improve pharmacodynamic target attainment 5
3. Continuous infusion: May provide the highest probability of achieving pharmacodynamic targets (65-81% vs. 21-68% with intermittent dosing) 5, 6

Combination Therapy Considerations

For serious Pseudomonas infections, combination therapy may be beneficial:

• Consider adding an aminoglycoside (tobramycin 5-7 mg/kg IV once daily or amikacin 15-20 mg/kg IV once daily) for severe infections 2, 3
• Combination therapy with tobramycin has demonstrated enhanced killing of both mucoid and non-mucoid P. aeruginosa isolates 7
• For multi-drug resistant Pseudomonas, combination therapy with two active agents from different classes is recommended 2

Treatment Duration

• For serious Pseudomonas infections: 7-14 days based on clinical response 2
• For pneumonia due to Pseudomonas: 10 days 1
• For complicated intra-abdominal infections: 7-10 days 1

Clinical Pearls and Pitfalls

• Pitfall: Underdosing cefepime against Pseudomonas can lead to treatment failure. The standard 2g every 12 hours regimen may be insufficient for Pseudomonas infections 4, 5
• Pitfall: Failing to adjust dosage in renal impairment can lead to toxicity
• Pearl: For isolates with higher MICs (≥4 μg/mL), more aggressive dosing (2g every 8 hours) or extended/continuous infusion should be considered 4, 5
• Pearl: Monitoring renal function is essential, as nephrotoxicity risk increases with prolonged therapy (>7 days), pre-existing renal impairment, and concomitant nephrotoxic agents 2

Future Considerations

Several cefepime/β-lactamase inhibitor combinations are in development for multi-drug resistant organisms:

• Cefepime/zidebactam and cefepime/taniborbactam show promising activity against carbapenemase-producing organisms 8
• These combinations may provide future options for difficult-to-treat Pseudomonas infections 8