How should meropenem be dosed in an adult patient based on creatinine clearance levels, intermittent hemodialysis, continuous renal replacement therapy, and augmented renal clearance?

Meropenem Renal Dose Adjustment

Meropenem requires dose reduction or interval extension in renal impairment because it is predominantly renally excreted, with elimination half-life prolonging from 1 hour in healthy individuals to up to 13.7 hours in anuric patients. 1

Standard Renal Dosing by Creatinine Clearance

CrCl >50 mL/min

• Use standard dosing: 1g IV every 8 hours or 500mg-1g every 8 hours depending on infection severity 2
• No adjustment needed for normal renal function 2

CrCl 30-50 mL/min

• Reduce to standard dose every 12 hours 2
• Example: 1g IV every 12 hours instead of every 8 hours 2

CrCl <30 mL/min

• Extend dosing interval to every 24 hours 2
• Use standard dose (500mg-1g) but given once daily 2

Intermittent Hemodialysis (IHD)

Administer meropenem after each hemodialysis session, as approximately 50% of the drug is removed during a dialysis session. 1, 2

• Recommended regimen: 500mg IV after each dialysis session 2
• Hemodialysis shortens meropenem half-life from 7.0 hours to 2.9 hours 2
• Timing is critical—dosing before dialysis results in significant drug loss 2

Continuous Renal Replacement Therapy (CRRT)

Patients on CRRT require substantially higher doses than standard renal dosing because hemofiltration contributes significantly to meropenem elimination. 3

CVVH (Continuous Venovenous Hemofiltration)

• Recommended dose: 500mg IV every 8 hours or 1g every 12 hours 3
• CVVH removes 25-50% of meropenem, with hemofiltration clearance of approximately 22 mL/min 1, 3
• Standard renal failure dosing leads to underdosing—increase dose by 100% compared to anuric patients not on CRRT 3

CVVHDF (Continuous Venovenous Hemodiafiltration)

• Similar dosing to CVVH: 500mg every 8 hours 1
• CVVHDF removes 13-53% of meropenem depending on dialysate and ultrafiltrate rates 1
• Wide variability in clearance necessitates consideration of therapeutic drug monitoring 1

Key CRRT Considerations

• Peak concentrations on CRRT range from 18-45 mg/L after 1g dose, compared to 53-62 mg/L in healthy volunteers 1
• Trough concentrations of 7.3-11.9 mg/L are achieved with 500mg every 8-12 hours 3
• The excellent tolerability profile of meropenem means underdosing should be avoided—err on the side of higher doses in CRRT 1

Augmented Renal Clearance (ARC)

Critically ill patients with CrCl ≥90 mL/min require dose escalation, increased frequency, prolonged infusion duration, or continuous infusion to achieve adequate drug exposure. 4

CrCl 90-130 mL/min

• Increase to 6g/day total (e.g., 2g IV every 8 hours) 4
• Standard dosing achieves suboptimal coverage for MIC90 targets 4

CrCl >130 mL/min

• Consider extended infusion (3-4 hours) or continuous infusion of 3-6g/day 4
• Recommended regimens are inadequate in patients with normal or augmented clearance using standard infusion times 4
• Target 100% time above MIC for optimal bactericidal activity 4

Critical Monitoring Considerations

Therapeutic Drug Monitoring (TDM)

• TDM is highly beneficial for critically ill patients, especially those with ARC or on CRRT, to avoid under/overdosing 5
• Significant pharmacokinetic variability exists in ICU patients 4

Creatinine Clearance Measurement

• Measured 24-hour creatinine clearance (mCLCR) is the most accurate method for calculating proper meropenem dosing 5
• eGFR equations (CKD-EPI, Cockcroft-Gault, MDRD) overestimate or underestimate actual clearance and lead to dosing errors 5
• CKD-EPI overestimates mCLCR up to 90 mL/min, then underestimates it 5

Common Pitfalls

• Do not use standard renal failure dosing for patients on CRRT—this leads to significant underdosing 3
• Do not assume standard dosing is adequate in critically ill patients with preserved renal function—many have ARC requiring dose escalation 4
• Do not rely on estimated GFR equations in ICU patients—they correlate poorly with actual drug clearance 5
• Do not dose meropenem before hemodialysis—wait until after the session to avoid drug removal 2