Cefepime Dosage Adjustment in Acute Kidney Injury
For patients with acute kidney injury (AKI), cefepime dosage should be adjusted based on creatinine clearance, with specific recommendations of 500 mg every 24 hours for CrCl 11-29 mL/min and 250 mg every 24 hours for CrCl less than 11 mL/min.
Dosage Recommendations Based on Renal Function
The FDA-approved drug label for cefepime provides clear guidance for dosage adjustment in patients with renal impairment 1:
| Creatinine Clearance (mL/min) | Standard Dose (1g q12h) | High Dose (2g q12h) | Maximum Dose (2g q8h) |
|---|---|---|---|
| 30-60 | 1g every 24h | 2g every 24h | 2g every 12h |
| 11-29 | 500mg every 24h | 1g every 24h | 2g every 24h |
| <11 | 250mg every 24h | 500mg every 24h | 1g every 24h |
Determining Renal Function in AKI
When assessing renal function in AKI patients:
Use the Cockcroft-Gault equation to estimate creatinine clearance 1:
- Males: CrCl (mL/min) = Weight (kg) × (140 - age) / (72 × serum creatinine [mg/dL])
- Females: CrCl (mL/min) = 0.85 × above value
For staging AKI, follow the KDIGO criteria 2, 3:
- Stage 1: Increase in SCr ≥0.3 mg/dL within 48h or 1.5-1.9 times baseline
- Stage 2: Increase in SCr 2.0-2.9 times baseline
- Stage 3: Increase in SCr ≥3.0 times baseline or ≥4.0 mg/dL or requiring RRT
Special Considerations for AKI Patients
Early AKI with potential for recovery: Consider that approximately 57.2% of AKI cases resolve within 48 hours 4. In patients with wide therapeutic index antibiotics, some evidence suggests that immediate dose reduction may not be necessary if recovery is anticipated.
Hemodialysis patients: For patients on hemodialysis, administer 1g on day 1, followed by 500 mg every 24 hours thereafter, with doses given after hemodialysis sessions 1.
Continuous renal replacement therapy (CRRT): For patients on CVVHD, higher doses may be required - a study suggests 2g twice daily may be appropriate due to significant clearance during CRRT 5.
Monitoring Recommendations
Monitor serum creatinine daily during the acute phase of AKI to assess kidney function recovery or deterioration 3.
Assess clinical response to therapy and adjust dosing if needed based on changes in renal function.
Monitor for signs of cefepime toxicity, particularly neurotoxicity, which can occur with inappropriate dosing in renal impairment.
Pitfalls to Avoid
Overestimation of renal function: Standard equations may overestimate GFR in critically ill patients with AKI. One study showed poor precision of urinary creatinine clearance with high error rates compared to measured GFR 6.
Premature dose reduction: Early dose reduction in fluctuating AKI may lead to subtherapeutic antibiotic levels if renal function improves rapidly 4.
Failure to reassess: Kidney function can change rapidly in AKI, requiring frequent reassessment and dose adjustment.
Inadequate loading dose: Even in severe renal impairment, a full loading dose is typically recommended to rapidly achieve therapeutic concentrations.
By following these evidence-based recommendations for cefepime dosing in AKI, clinicians can optimize antimicrobial therapy while minimizing the risk of toxicity in this vulnerable patient population.