What is the recommended dosing for cefepime in adults with normal and impaired renal function?

Cefepime Dosing Recommendations for Adults

For adult patients with normal renal function, cefepime should be dosed at 1-2 g IV every 8-12 hours, with dosage adjustments required for patients with impaired renal function. 1

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

• For moderate to severe infections (including pneumonia due to S. pneumoniae, P. aeruginosa, K. pneumoniae, or Enterobacter species): 1-2 g IV every 8-12 hours for 10 days 1
• For empiric therapy in febrile neutropenic patients: 2 g IV every 8 hours for 7 days or until resolution of neutropenia 1
• For mild to moderate uncomplicated or complicated urinary tract infections: 0.5-1 g IV every 12 hours for 7-10 days 1
• For severe uncomplicated or complicated urinary tract infections: 2 g IV every 12 hours for 10 days 1
• For moderate to severe skin and skin structure infections: 2 g IV every 12 hours for 10 days 1
• For complicated intra-abdominal infections (used with metronidazole): 2 g IV every 8-12 hours for 7-10 days 1

Dosing for Adults with Impaired Renal Function

Creatinine Clearance 30-60 mL/min:

• 500 mg every 24 hours (if normal dose is 500 mg q12h) 1
• 1 g every 24 hours (if normal dose is 1 g q12h) 1
• 2 g every 24 hours (if normal dose is 2 g q12h) 1
• 2 g every 12 hours (if normal dose is 2 g q8h) 1

Creatinine Clearance 11-29 mL/min:

• 500 mg every 24 hours (if normal dose is 500 mg q12h) 1
• 500 mg every 24 hours (if normal dose is 1 g q12h) 1
• 1 g every 24 hours (if normal dose is 2 g q12h) 1
• 2 g every 24 hours (if normal dose is 2 g q8h) 1

Creatinine Clearance <11 mL/min:

• 250 mg every 24 hours (if normal dose is 500 mg q12h) 1
• 250 mg every 24 hours (if normal dose is 1 g q12h) 1
• 500 mg every 24 hours (if normal dose is 2 g q12h) 1
• 1 g every 24 hours (if normal dose is 2 g q8h) 1

Special Populations

Hemodialysis Patients:

• Initial dose of 1 g on day 1, then 500 mg every 24 hours thereafter (for most infections) 1
• For febrile neutropenia: 1 g every 24 hours 1
• Administer cefepime after completion of hemodialysis on dialysis days 1

Continuous Ambulatory Peritoneal Dialysis (CAPD) Patients:

• 500 mg every 48 hours (if normal dose is 500 mg q12h) 1
• 1 g every 48 hours (if normal dose is 1 g q12h) 1
• 2 g every 48 hours (if normal dose is 2 g q12h or 2 g q8h) 1

Administration Considerations

• Standard administration: Infuse over approximately 30 minutes 1
• Extended or continuous infusions may be beneficial for infections due to bacteria with high MICs to increase probability of achieving pharmacokinetic/pharmacodynamic targets 2
• For serious infections such as bacteremia, infective endocarditis, and pneumonia, higher doses within the recommended range should be considered 2

Safety Considerations

• Cefepime has been associated with neurotoxicity, particularly in patients with renal impairment, even when dosage adjustments are made 3, 4
• Signs of neurotoxicity include altered mental status, confusion, hallucinations, and seizures 3
• Risk factors for neurotoxicity include severe renal dysfunction, higher cefepime doses, and critical illness 4
• Therapeutic drug monitoring may be beneficial in critically ill patients, those with life-threatening infections, or patients infected with resistant pathogens 5
• Cefepime has relatively high pro-convulsive activity compared to other beta-lactams (160 on a relative scale where penicillin G = 100) 2

Monitoring Recommendations

• Monitor renal function regularly during therapy, especially in critically ill patients whose renal function may fluctuate 6
• Consider dose reduction if deterioration in renal function occurs during treatment 1, 6
• For patients on CRRT, higher doses may be required than typically recommended for patients with renal impairment not on CRRT 7
• Monitor for signs of neurotoxicity, particularly in patients with renal impairment receiving higher doses 3, 4

By following these dosing recommendations and monitoring parameters, clinicians can optimize cefepime therapy to achieve therapeutic efficacy while minimizing the risk of adverse effects, particularly neurotoxicity in patients with renal impairment.