Can cefepime (Cefipime) be administered twice daily (BID) at a higher dose?

Cefepime Administration at Higher Doses with BID Dosing

Cefepime can be administered twice daily (BID) at higher doses (2g every 12 hours) for certain infections, but this approach is not recommended for all situations and should be guided by the specific infection, pathogen susceptibility, and patient renal function. 1, 2

Standard Dosing Recommendations

The FDA-approved dosing for cefepime varies based on the type and severity of infection:

• For serious infections in adults:

  • Standard dosing: 2g IV every 8-12 hours 1
  • For febrile neutropenia: 2g IV every 8 hours 1
  • For complicated intra-abdominal infections: 2g IV every 8-12 hours 1

• For uncomplicated/complicated urinary tract infections:

  • Mild to moderate: 0.5-1g IV every 12 hours 1
  • Severe: 2g IV every 12 hours 1

When BID Dosing at Higher Doses is Appropriate

BID dosing at 2g every 12 hours is FDA-approved and appropriate for:

• Moderate to severe uncomplicated skin and skin structure infections 1
• Severe uncomplicated or complicated urinary tract infections 1
• Some complicated intra-abdominal infections 1

Pharmacokinetic/Pharmacodynamic Considerations

Beta-lactams like cefepime require maintaining concentrations above the MIC for at least 60-70% of the dosing interval for optimal bactericidal activity 2. This has important implications for dosing frequency:

• Cefepime has a relatively short half-life of approximately 2 hours 3, 4
• Higher doses (2g) with BID dosing can maintain adequate concentrations for susceptible organisms with MICs ≤4 mg/L 5
• For pathogens with higher MICs (≥8 mg/L), BID dosing may not provide adequate coverage, with only 45-65% of patients achieving appropriate T>MIC 5

Special Considerations and Warnings

1. Renal function impacts:

   • BID dosing at higher doses requires normal renal function (CrCl >60 mL/min) 1
   • Patients with impaired renal function (CrCl ≤60 mL/min) require dose adjustment and potentially extended intervals 1
   • Accumulation can occur in patients with severe renal impairment, potentially leading to neurotoxicity 5

2. Pathogen considerations:

   • For infections caused by organisms with MICs ≤4 mg/L, BID dosing at 2g provides adequate coverage 5
   • For suspected or confirmed pathogens with higher MICs (≥8 mg/L), more frequent dosing (every 8 hours) is preferred 2, 5

3. Infection site considerations:

   • For serious infections like febrile neutropenia, every 8-hour dosing is recommended 2, 1
   • For prosthetic valve endocarditis, 2g every 8 hours is recommended 2

Administration Techniques to Optimize Efficacy

For serious infections where BID dosing is used:

• Extended infusions over 3-4 hours rather than bolus dosing may improve pharmacodynamic exposure 2
• This approach helps maintain concentrations above the MIC for a longer portion of the dosing interval

Conclusion

While cefepime can be administered BID at higher doses (2g every 12 hours) for certain infections, this approach should be limited to:

1. Patients with normal renal function
2. Infections caused by pathogens with lower MICs (≤4 mg/L)
3. Specific FDA-approved indications

For more serious infections, particularly those involving Pseudomonas aeruginosa or other pathogens with higher MICs, the more frequent dosing regimen of 2g every 8 hours is preferred to ensure optimal efficacy and prevent treatment failure 2, 1, 5.