What are the recommended cefepime dosing regimens for adults (including adjustments for renal impairment) and children, and the appropriate treatment duration?

Cefepime Dosing Recommendations

Adult Dosing (Normal Renal Function)

For severe infections including nosocomial pneumonia, sepsis, and complicated intra-abdominal infections, administer cefepime 2g IV every 8 hours in critically ill adults with normal renal function. 1

Standard Dosing by Indication

• Severe pneumonia or Pseudomonas aeruginosa infections: 2g IV every 8 hours 1
• Healthcare-associated intra-abdominal infections: 2g IV every 8 hours plus metronidazole 500mg every 6 hours for 7-10 days 1
• Febrile neutropenia and sepsis: 2g IV every 8 hours 1
• Prosthetic valve endocarditis (early, ≤1 year): 6g per 24 hours IV in 3 equally divided doses (2g every 8 hours) for 6 weeks 2

Critical Dosing Considerations for Severe Infections

• Higher doses may be required for critically ill patients due to increased clearance and volume of distribution, with studies showing 37-44% of ICU patients fail to achieve therapeutic targets with standard dosing 1
• Doses exceeding 4g daily may be necessary for Pseudomonas infections with elevated MICs (≥4 mg/L) 1
• Extended infusions (3-4 hours) or continuous infusions should be considered for severe infections with high-MIC organisms (≥4 mg/L) to optimize time above MIC 1

Pediatric Dosing (≥2 Months to 16 Years)

For pediatric patients with normal renal function, administer 50 mg/kg every 8-12 hours (maximum 2g per dose) infused over 30 minutes. 1

Specific Pediatric Indications

• Complicated intra-abdominal infections: 100 mg/kg/day administered every 12 hours 3
• Prosthetic valve endocarditis: 150 mg/kg/day IV in 3 equally divided doses for 6 weeks 3
• Gram-negative enteric bacilli infections: 100-150 mg/kg/day IV divided every 8 hours (maximum 2-4g daily) 3
• Critically ill children with normal/augmented renal clearance: 100 mg/kg/day as continuous infusion 1

Pediatric Dosing Nuances

• Critically ill children with normal or augmented renal clearance require continuous infusions to achieve pharmacokinetic targets, while intermittent infusions are adequate for children with acute renal failure 4
• Close therapeutic drug monitoring is mandatory given cefepime's narrow therapeutic window in pediatric ICU patients 4

Renal Impairment Adjustments

Dose adjustments are critical in renal impairment to prevent neurotoxicity while maintaining efficacy.

Dosing by Creatinine Clearance

• CrCl ≥50 mL/min: 2g every 12 hours (standard dose) 5
• CrCl 30-50 mL/min: 2g every 24 hours 5
• CrCl <30 mL/min: 2g every 36 hours 5

Critical Safety Considerations in Renal Impairment

• Monitor for neurotoxicity (confusion, encephalopathy, myoclonus, seizures) especially when trough concentrations exceed 8× MIC 1
• Accumulation can occur despite dose adjustment in patients with CrCl <30 mL/min, with trough concentrations reaching 20-30 mg/L and causing non-convulsive epilepsy symptoms 5
• Therapeutic drug monitoring should be strongly considered in patients with fluctuating renal function or CrCl <50 mL/min 1, 5

Administration Strategies

Standard vs. Extended Infusions

• Standard infusion: 30-60 minutes for routine infections 1, 6
• Extended infusion: 3-4 hours for severe infections, particularly with Pseudomonas or MIC ≥4 mg/L 1
• Continuous infusion: Consider for critically ill patients with sepsis, with a loading dose given as rapid bolus followed by continuous infusion 1

Pharmacokinetic/Pharmacodynamic Targets

• Goal exposure: 70-100% time of free drug concentration above MIC for clinical efficacy 6
• For severe infections: Target 100% T>MIC, which may require extended or continuous infusions 1
• Risk-benefit decreases when trough concentrations exceed 8× MIC due to neurotoxicity risk 1

Treatment Duration

• Prosthetic valve endocarditis: 6 weeks 2
• Healthcare-associated intra-abdominal infections: 7-10 days 1
• Other severe infections: Duration depends on clinical response and source control 1

Common Pitfalls to Avoid

• Do not use standard dosing in critically ill patients with normal renal function—they require higher doses (2g every 8 hours) due to increased clearance 1
• Do not overlook neurotoxicity in renal impairment—symptoms may be subtle (confusion, muscle jerks) and not immediately attributed to cefepime 5
• Do not assume adequate coverage for pathogens with MIC ≥8 mg/L with standard dosing—only 45-65% of patients achieve appropriate coverage 5
• Do not use intermittent infusions in critically ill children with augmented renal clearance—continuous infusions are required 4