Cefepime and Sulbactam Dosage Adjustments in Acute Kidney Injury
For patients with acute kidney injury (AKI), cefepime dosing should be reduced based on creatinine clearance, with 250-500 mg every 24 hours for severe AKI (CrCl <11 mL/min) and sulbactam dosing should follow a similar reduction pattern with administration every 24 hours in severe AKI. 1
Cefepime Dosage Adjustment in AKI
Cefepime requires significant dosage adjustment in patients with renal impairment due to its primary elimination through the kidneys. The FDA-approved dosing guidelines provide clear recommendations based on creatinine clearance:
| Creatinine Clearance (mL/min) | Recommended Cefepime Dosing |
|---|---|
| >60 mL/min | 500 mg-2 g every 8-12 hours (normal dosing) |
| 30-60 mL/min | 500 mg-2 g every 24 hours |
| 11-29 mL/min | 500 mg-1 g every 24 hours |
| <11 mL/min | 250-500 mg every 24 hours |
| CAPD | 500 mg-2 g every 48 hours |
| Hemodialysis | 1 g on day 1, then 500 mg-1 g every 24 hours (administer after dialysis) |
Important Considerations for Cefepime in AKI
Risk of neurotoxicity: Cefepime accumulation in renal impairment can lead to serious neurotoxicity including encephalopathy, myoclonus, seizures, and coma. Studies show this occurs more frequently when doses aren't properly adjusted for renal function 2.
Monitoring: Patients with AKI receiving cefepime should be monitored for neurological symptoms including altered mental status, confusion, and myoclonus, which are early signs of cefepime neurotoxicity.
Estimation of renal function: While the Cockcroft-Gault equation is traditionally used for drug dosing, the Modified Jelliffe equation may be more accurate in AKI settings 3. However, the FDA label specifically recommends using Cockcroft-Gault for cefepime dosing 1.
Sulbactam (Dulbactam) Dosage Adjustment in AKI
Sulbactam, like ampicillin with which it's often combined, requires significant dosage adjustment in renal impairment:
Normal to mild renal impairment (CrCl >30 mL/min): Standard dosing can be maintained.
Moderate to severe renal impairment (CrCl 7-30 mL/min): Reduce frequency to twice daily 4.
End-stage renal disease (CrCl <7 mL/min): Administer every 24 hours. On hemodialysis days, administer after dialysis to prevent premature removal of the drug 4.
Extended dialysis: For patients on extended dialysis, a twice-daily dosing schedule of ampicillin/sulbactam should be used, with one dose given after dialysis 5.
Staging AKI and Implications for Dosing
The KDIGO guidelines define AKI stages based on serum creatinine and urine output 6:
| AKI Stage | Serum Creatinine Criteria | Urine Output Criteria |
|---|---|---|
| 1 | 1.5-1.9× baseline or ≥0.3 mg/dL increase | <0.5 mL/kg/h for 6-12h |
| 2 | 2.0-2.9× baseline | <0.5 mL/kg/h for ≥12h |
| 3 | 3.0× baseline or increase to ≥4.0 mg/dL or initiation of RRT | <0.3 mL/kg/h for ≥24h or anuria for ≥12h |
When determining dosing in AKI:
Calculate creatinine clearance using the Cockcroft-Gault equation:
- Males: CrCl (mL/min) = [Weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)]
- Females: CrCl (mL/min) = 0.85 × male value 1
Adjust dosing based on calculated CrCl using the tables above.
Reassess frequently: AKI is dynamic, with kidney function potentially changing rapidly. Studies show kidney function can change by an average of 30 mL/min over the course of an AKI episode 3.
Special Considerations
Continuous renal replacement therapy (CRRT): For patients on CRRT, cefepime clearance is affected by effluent flow rates. Studies in pediatric patients show clearance of approximately 3.0 L/h/70kg with effluent flow rates of 2600 mL/1.73m²/h 7. Adult dosing should be adjusted accordingly.
Temporary discontinuation: Consider temporary discontinuation of potentially nephrotoxic drugs during serious intercurrent illness that increases AKI risk 6.
Hemodialysis: Both cefepime and sulbactam are significantly removed during hemodialysis (68% of cefepime and 44.7% of sulbactam during a 4-hour session) 1, 4. Always administer doses after dialysis.
Drug interactions: Avoid concurrent use of other nephrotoxic agents when possible to prevent worsening of AKI.
Practical Algorithm for Dosing in AKI
- Determine AKI stage using KDIGO criteria 6
- Calculate CrCl using Cockcroft-Gault equation
- Adjust cefepime dose according to CrCl:
- CrCl 30-60 mL/min: 1-2 g every 24 hours
- CrCl 11-29 mL/min: 500 mg-1 g every 24 hours
- CrCl <11 mL/min: 250-500 mg every 24 hours
- Adjust sulbactam dose according to CrCl:
- CrCl 30-60 mL/min: Standard dose every 12-24 hours
- CrCl 7-30 mL/min: Standard dose twice daily
- CrCl <7 mL/min: Standard dose every 24 hours
- Monitor renal function daily and adjust dosing as needed
- Monitor for signs of neurotoxicity with cefepime
By following these guidelines, clinicians can optimize antimicrobial therapy while minimizing the risks of drug toxicity in patients with AKI.