What is the recommended meropenem dosing for an adult with impaired renal function based on creatinine clearance (CrCl)?

Meropenem Dosing in Renal Insufficiency

For adults with renal impairment, meropenem dosing must be adjusted based on creatinine clearance (CrCl), with the critical principle being to extend the dosing interval rather than reduce individual doses below 1 gram when treating serious infections, maintaining standard doses per administration to preserve concentration-dependent bactericidal activity. 1, 2

Standard Dosing Adjustments by Creatinine Clearance

The FDA-approved dosing schedule for adults with renal impairment is as follows 2:

• CrCl >50 mL/min: Standard dose (500 mg for complicated skin/skin structure infections [cSSSI], 1 gram for intra-abdominal infections) every 8 hours
• CrCl 26-50 mL/min: Recommended dose every 12 hours (instead of every 8 hours)
• CrCl 10-25 mL/min: One-half recommended dose every 12 hours
• CrCl <10 mL/min: One-half recommended dose every 24 hours

Important caveat: When treating Pseudomonas aeruginosa infections in cSSSI, use 1 gram every 8 hours regardless of the infection type 2.

Critical Dosing Principles for Serious Infections

The Infectious Diseases Society of America emphasizes maintaining individual doses at 1 gram or higher for serious infections, even in renal impairment, by extending the dosing interval rather than reducing the dose per administration. 1 This approach is crucial because:

• Meropenem exhibits concentration-dependent bactericidal activity 1
• Reducing individual doses below 1 gram may result in inadequate peak concentrations and treatment failure
• Extended infusion (over 3 hours) or continuous infusion should be considered for organisms with MIC ≥4 mg/L 1

Pharmacokinetic Considerations in Renal Failure

The elimination half-life of meropenem increases dramatically with declining renal function 3, 4:

• Normal renal function: approximately 1 hour 1, 3
• Moderate impairment (CrCl 30-50 mL/min): 3.4 hours 4
• Severe impairment (CrCl <30 mL/min): 5.0 hours 4
• End-stage renal disease (anuric): up to 13.7 hours 3

Approximately 77% of meropenem is excreted unchanged in urine in patients with normal renal function, decreasing proportionally with declining kidney function 5.

Dosing in Dialysis Patients

Intermittent Hemodialysis (IHD)

The FDA label states there is inadequate information for specific dosing recommendations in hemodialysis patients 2. However, research evidence demonstrates:

• Hemodialysis removes approximately 50% of meropenem 3
• The elimination half-life shortens from 9.7 hours pre-dialysis to 1.4-2.9 hours during dialysis 4, 5
• Dosing after each hemodialysis session is recommended 4

Continuous Renal Replacement Therapy (CRRT)

For patients on sustained low-efficiency dialysis (SLED), the American Thoracic Society recommends maintaining the full 1 gram dose every 12 hours rather than reducing individual doses below 1 gram. 1

For continuous venovenous hemofiltration (CVVHF) 6:

• Hemofiltration clearance contributes 22 mL/min to total clearance of 52 mL/min
• Approximately 47% of the dose is removed through CVVHF
• The recommended dose should be increased by 100% (to 1 gram every 8-12 hours) to avoid underdosing 6

Different CRRT modalities remove varying amounts of meropenem 3:

• CVVHF: 25-50% removal
• CVVHDF: 13-53% removal
• These differences necessitate careful consideration of the specific CRRT modality being used

Recent population pharmacokinetic data suggests that for Chinese critically ill CRRT patients with CrCl 10-50 mL/min, optimal regimens are 0.5 g every 6 hours or 1 g every 8 hours (both as 3-hour infusions) for MIC ≤4 mg/L 7.

Therapeutic Drug Monitoring and Toxicity Prevention

The American College of Clinical Pharmacy recommends maintaining trough concentrations below 64 mg/L to prevent neurological toxicity, particularly in critically ill patients with renal impairment. 1

Risk factors for neurotoxicity include 3:

• Accumulation in severe renal impairment
• Inadequate dose reduction in patients with CrCl <30 mL/min
• Concurrent CNS pathology or seizure history

Calculating Creatinine Clearance

Use the Cockcroft-Gault equation for dosing adjustments 2:

Males: CrCl (mL/min) = [Weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)]

Females: 0.85 × male value

The American Thoracic Society/CDC/Infectious Diseases Society of America guidelines emphasize using creatinine clearance rather than serum creatinine alone for accurate dosing adjustments 8.

Common Pitfalls to Avoid

1. Never reduce individual doses below 1 gram for serious infections - instead extend the dosing interval 1
2. Do not use eGFR directly for drug dosing without converting to absolute clearance - this can lead to underdosing in larger patients and overdosing in smaller patients 8
3. Avoid forgetting post-dialysis supplemental doses in hemodialysis patients - approximately 50% of the drug is removed during dialysis 3, 4
4. Do not assume all CRRT modalities remove the same amount of drug - removal varies from 13-53% depending on the specific technique 3
5. Monitor for neurotoxicity in patients with severe renal impairment - keep trough levels <64 mg/L 1

Administration Considerations

• Administer as IV infusion over 15-30 minutes for standard dosing 2
• 1 gram doses may be given as IV bolus over 3-5 minutes 2
• Consider extended infusion (3 hours) for organisms with MIC ≥4 mg/L or in critically ill patients 1, 7
• Do not mix with other drugs in the same solution 2