Meropenem Dosing in Chronic Kidney Disease
For patients with CKD, meropenem requires mandatory dose reduction based on creatinine clearance, with both dose amount and dosing interval adjusted according to renal function. 1
Standard Dosing Adjustments for Adults with CKD
The FDA-approved dosing schedule for meropenem in adults with renal impairment is as follows 1:
- CrCl >50 mL/min: Full dose (500 mg for cSSSI, 1 gram for intra-abdominal infections) every 8 hours
- CrCl 26-50 mL/min: Full recommended dose every 12 hours
- CrCl 10-25 mL/min: Half the recommended dose every 12 hours
- CrCl <10 mL/min: Half the recommended dose every 24 hours
For Pseudomonas aeruginosa infections specifically, use 1 gram every 8 hours regardless of infection type in patients with normal renal function, with corresponding adjustments for CKD. 1
Critical Considerations for Hemodialysis Patients
The FDA label explicitly states there is inadequate information regarding meropenem use in patients on hemodialysis or peritoneal dialysis. 1 However, research evidence provides guidance: approximately 50% of meropenem is removed during intermittent hemodialysis sessions 2, and the elimination half-life shortens from 7.0 hours to 2.9 hours during dialysis 3.
Based on pharmacokinetic studies, dosing after each hemodialysis session is recommended for patients receiving intermittent hemodialysis. 3 The general principle for antibiotic administration in hemodialysis patients is to give the dose post-dialysis to prevent drug removal during the dialysis session 4.
Pediatric Dosing Adjustments
There is no experience in pediatric patients with renal impairment, and the FDA label provides no specific dosing recommendations for this population. 1 This represents a significant knowledge gap requiring extreme caution when treating pediatric CKD patients with meropenem.
Calculating Creatinine Clearance
Use the Cockcroft-Gault equation to estimate creatinine clearance when only serum creatinine is available 1:
- Males: CrCl (mL/min) = [Weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)]
- Females: 0.85 × male calculation
While CKD-EPI may be superior for clinical risk stratification in cardiac patients 5, the FDA label specifically references Cockcroft-Gault for meropenem dosing adjustments 1.
Pharmacokinetic Rationale
The elimination half-life of meropenem increases progressively with declining renal function: from approximately 1 hour in healthy volunteers to 1.54 hours with CrCl >50 mL/min, 3.36 hours with CrCl 30-50 mL/min, 5.00 hours with CrCl <30 mL/min, and up to 13.7 hours in anuric patients 2, 3. This prolonged half-life necessitates dose reduction to prevent drug accumulation and potential toxicity. 2
Cumulative urinary excretion accounts for 48.5% of the dose in patients with mild renal impairment and decreases progressively as renal function declines 3. Meropenem exposure increases significantly with declining kidney function, requiring careful dose adjustment to maintain therapeutic levels without toxicity. 6
Continuous Renal Replacement Therapy (CRRT)
For critically ill patients receiving continuous venovenous hemofiltration (CVVHF), hemofiltration clearance is approximately 22 mL/min, with 47% of the dose removed through CVVHF 7. The recommended dose for anuric patients receiving CVVHF should be increased by 100% compared to standard renal failure dosing to avoid underdosing. 7
Different CRRT modalities remove varying amounts of meropenem: 25-50% by CVVHF and 13-53% by continuous venovenous hemodiafiltration (CVVHDF) 2. These differences are clinically significant and demonstrate the substantial influence of treatment modality on drug elimination. 2
Common Pitfalls to Avoid
Do not use standard dosing in patients with any degree of renal impairment—even mild CKD requires assessment and potential adjustment. 1 The excellent tolerability profile of meropenem should not lead to complacency about underdosing, as subtherapeutic levels may result in treatment failure and resistance development 2.
Avoid extrapolating dosing recommendations between different renal replacement modalities, as pharmacokinetic parameters vary substantially between intermittent hemodialysis, CVVHF, CVVHDF, and peritoneal dialysis 2.
Note on Sulbactam
The evidence provided does not contain specific information about sulbactam dosing in CKD. Sulbactam is a beta-lactamase inhibitor typically combined with other antibiotics (such as ampicillin or cefoperazone), and its dosing in renal impairment would require separate evaluation based on its specific pharmacokinetic properties and FDA labeling.