Cefepime Dosing for Prosthetic Joint Infection
For prosthetic joint infection (PJI) with normal renal function, administer cefepime 2 g IV every 8 hours as part of empirical therapy, typically combined with vancomycin and gentamicin (with or without rifampin if prosthetic material is present). 1
Empirical Therapy Regimen
The American Heart Association guidelines for prosthetic material infections provide the framework for cefepime dosing in PJI:
- Standard dose: 2 g IV every 8 hours 1
- Maximum daily dose: Up to 6 g/day (100-150 mg/kg/day in pediatrics) 1
- Infusion time: 30 minutes for standard administration 2
- Duration: 4-6 weeks of IV therapy following definitive surgical intervention 3
Combination Therapy Strategy
For nosocomial or early prosthetic infections (≤1 year after surgery), cefepime should be combined with: 1
- Vancomycin 60 mg/kg/day IV divided every 6 hours (up to 2 g) 1
- Gentamicin 3-6 mg/kg/day IV divided every 8 hours 1
- Rifampin 20 mg/kg/day divided every 8 hours (up to 900 mg/day) if prosthetic material present 1
Critical Dosing Considerations
Enhanced Dosing for Severe Infections
For critically ill patients or infections with high-MIC organisms (≥4 mg/L), consider extended infusions (3-4 hours) to optimize time above MIC. 2
- Extended infusions improve pharmacokinetic/pharmacodynamic target attainment, particularly for Pseudomonas infections 2
- Doses exceeding 4 g daily may be required for Pseudomonas with elevated MICs 2
Renal Function Adjustments
For patients with creatinine clearance ≤60 mL/min, adjust dosing as follows: 4
| CrCl (mL/min) | Dose | Interval |
|---|---|---|
| 30-60 | 2 g | Every 24 hours |
| 11-29 | 1 g | Every 24 hours |
| <11 | 500 mg | Every 24 hours |
| Hemodialysis | 1 g day 1, then 500 mg | Every 24 hours (after dialysis) |
Safety and Monitoring
Cefepime combined with vancomycin demonstrates superior renal safety compared to piperacillin/tazobactam with vancomycin. 5
- Acute kidney injury occurred in only 6.7% with cefepime+vancomycin versus 25.8% with piperacillin/tazobactam+vancomycin 5
- Monitor for neurotoxicity (confusion, encephalopathy, myoclonus, seizures), especially when trough concentrations exceed 8× MIC 2
- Daily renal function assessment is mandatory 3
Microbiological Efficacy
The empirical regimen provides excellent coverage for PJI pathogens:
- Gram-positive coverage: Staphylococci (including MRSA via vancomycin) 1
- Gram-negative coverage: Enterobacteriaceae and Pseudomonas aeruginosa 1
- Microbiological efficacy of cefepime-based empirical therapy was 98.5% in documented PJI cases 5
Important Caveats
- Cefepime does not provide adequate anaerobic coverage; add metronidazole 500 mg IV every 6 hours if anaerobic infection suspected 2
- For mucoid Pseudomonas strains, monotherapy may be insufficient despite adequate drug concentrations; combination therapy with aminoglycoside is essential 6
- Time above MIC should be ≥60% of the dosing interval for optimal bactericidal activity 7
Surgical Coordination
Antimicrobial therapy must be coordinated with surgical management: 3