Meropenem Dosing in Acute Kidney Injury
In patients with AKI, reduce meropenem dose based on creatinine clearance: use the recommended dose (500 mg or 1 gram depending on infection) every 12 hours for CrCl 26-50 mL/min, half the recommended dose every 12 hours for CrCl 10-25 mL/min, and half the recommended dose every 24 hours for CrCl <10 mL/min. 1
Standard Dosing Adjustments by Renal Function
The FDA-approved dosing algorithm for meropenem in renal impairment is straightforward and based on creatinine clearance 1:
- CrCl >50 mL/min: Standard dosing (500 mg every 8 hours for skin/soft tissue infections; 1 gram every 8 hours for intra-abdominal infections) 1
- CrCl 26-50 mL/min: Use the full recommended dose but extend interval to every 12 hours 1
- CrCl 10-25 mL/min: Use half the recommended dose every 12 hours 1
- CrCl <10 mL/min: Use half the recommended dose every 24 hours 1
Estimating Creatinine Clearance
When only serum creatinine is available, use the Cockcroft-Gault equation 1:
- Males: CrCl (mL/min) = [Weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)] 1
- Females: Multiply the male calculation by 0.85 1
Special Considerations for Continuous Renal Replacement Therapy
For critically ill patients with AKI receiving continuous venovenous hemofiltration (CVVHF) or continuous hemodiafiltration (CHDF), increase the standard dose by 100% to avoid underdosing, as hemofiltration significantly contributes to meropenem elimination. 2
The pharmacokinetic data support this recommendation:
- CVVHF removes approximately 47% of the meropenem dose, with hemofiltration clearance of 22 mL/min contributing substantially to total drug clearance of 52 mL/min 2
- Recommended dosing for CVVHF: 500 mg every 8 hours or 1 gram every 12 hours achieves adequate plasma concentrations for bacteria with MIC ≤2 mg/L 3
- The terminal elimination half-life extends to 8.7 hours in anuric patients receiving CVVHF, compared to 1 hour in healthy volunteers 2
Alternative CRRT Dosing Strategies
For patients on CHDF specifically, population pharmacokinetic modeling supports 3:
- 500 mg every 8 hours OR
- 1 gram every 12 hours
Both regimens achieve 100% time above MIC for susceptible organisms 3
Important Clinical Caveats
Avoid combining vancomycin with meropenem when possible in trauma patients, as this combination significantly increases AKI risk (38% incidence) compared to vancomycin plus cefepime (19% incidence). 4 The odds ratio for AKI with vancomycin-meropenem combination is 4.4 (95% CI 1.4-12) 4
Monitor renal function closely during therapy, as even small increases in serum creatinine (≥0.3 mg/dL or ≥1.5 times baseline) define AKI and warrant dose adjustment 5
The FDA label notes inadequate information for patients on intermittent hemodialysis or peritoneal dialysis, so clinical judgment and therapeutic drug monitoring should guide dosing in these scenarios 1
Pediatric Dosing Adjustments
For pediatric patients ≥3 months with normal renal function 1:
- Complicated skin/soft tissue infections: 10 mg/kg (max 500 mg) every 8 hours 1
- Complicated intra-abdominal infections: 20 mg/kg (max 1 gram) every 8 hours 1
There is no established experience for dose adjustment in pediatric patients with renal impairment, requiring extrapolation from adult dosing principles 1