How should meropenem (Carbapenem antibiotic) be dosed in patients with Chronic Kidney Disease (CKD) and Impaired Renal Function?

Meropenem Dosing in Chronic Kidney Disease

Meropenem dosing should be reduced in patients with CKD based on creatinine clearance, with specific adjustments required for patients with CrCl ≤50 mL/min.

Dosing Recommendations Based on Renal Function

The FDA-approved dosing schedule for meropenem in adults with renal impairment is as follows:

• CrCl >50 mL/min: Standard dose (500 mg for cSSSI and 1 gram for intra-abdominal infections) every 8 hours 1
• CrCl 26-50 mL/min: Standard dose every 12 hours 1
• CrCl 10-25 mL/min: Half the recommended dose every 12 hours 1
• CrCl <10 mL/min: Half the recommended dose every 24 hours 1

Pharmacokinetic Considerations in CKD

• Meropenem is predominantly eliminated by the kidneys, with approximately 70% recovered unchanged in urine in patients with normal renal function 2
• The elimination half-life of meropenem increases progressively with declining renal function:
  • Normal renal function: ~1 hour
  • Moderate renal impairment: ~3.4 hours
  • Severe renal impairment: ~5 hours
  • End-stage renal disease: Up to 13.7 hours 3, 4

Special Considerations for Dialysis Patients

Hemodialysis

• Approximately 50% of meropenem is removed during hemodialysis 3
• Hemodialysis significantly shortens the elimination half-life from approximately 7 hours to 2.9 hours 4
• The FDA label notes inadequate information regarding meropenem use in hemodialysis patients 1, but based on pharmacokinetic studies, dosing after each hemodialysis session is recommended 4

Continuous Renal Replacement Therapy (CRRT)

• Different CRRT modalities affect meropenem clearance:
  • CVVHF removes approximately 25-50% of meropenem
  • CVVHDF removes approximately 13-53% of meropenem 3
• For critically ill anuric patients receiving CVVH, the dose may need to be increased by up to 100% compared to standard recommendations for anuric patients not on CRRT to avoid underdosing 5

Clinical Considerations

• Meropenem has a time-dependent bactericidal effect, so maintaining adequate drug concentrations above the MIC is crucial for efficacy 6
• Recent pharmacokinetic modeling suggests that exposure increases with declining kidney function, supporting the need for dose adjustments 6
• When treating serious infections in CKD patients, consider the severity of infection and susceptibility of the organism when determining the appropriate dose within the recommended ranges

Monitoring and Precautions

• Regular monitoring of renal function is recommended during meropenem therapy, especially in patients with fluctuating renal function
• For patients with both hepatic and renal impairment, careful monitoring is advised due to potential drug accumulation 1
• In patients with severe infections caused by less susceptible organisms, the higher end of the dosing range may be preferred while still adhering to renal adjustment guidelines

Practical Application

For a typical adult patient with CKD requiring meropenem:

1. Calculate or estimate creatinine clearance using the Cockcroft-Gault equation
2. Select appropriate dose and interval based on CrCl as outlined above
3. Consider the site and severity of infection when determining the base dose
4. Adjust therapy based on clinical response and microbiological data