What is the recommended dose of Meropenem (Meropenem) for a patient undergoing Continuous Renal Replacement Therapy (CRRT) with impaired renal function?

Meropenem Dosing in CRRT

For critically ill patients on CRRT, administer meropenem 500 mg every 8 hours as a 30-minute bolus for oligoanuric patients, or as a 3-hour extended infusion for patients with preserved residual diuresis (>100 mL/24h), targeting bacteria with MIC ≤2 mg/L. 1

Standard Dosing Recommendations

For Oligoanuric Patients (Minimal Residual Diuresis)

• Administer 500 mg every 8 hours as a 30-minute bolus for infections caused by susceptible organisms (MIC <2 mg/L) 1
• For organisms with MIC 2-4 mg/L (near resistance breakpoint), increase to 500 mg every 6 hours as a 30-minute bolus 1
• This dosing achieves adequate pharmacodynamic targets (40-100% fT>MIC) in patients without significant urine output 1

For Patients with Preserved Residual Diuresis

• Administer 500 mg every 8 hours as a 3-hour extended infusion for susceptible organisms (MIC <2 mg/L) 1
• For organisms with MIC 2-4 mg/L, increase to 500 mg every 6 hours as a 3-hour extended infusion 1
• Residual diuresis significantly increases meropenem clearance and is a critical dosing modifier 1

Key Pharmacokinetic Considerations

Impact of CRRT on Meropenem Elimination

• CRRT removes approximately 25-50% of meropenem through continuous venovenous hemofiltration (CVVHF) and 13-53% through continuous venovenous hemodiafiltration (CVVHDF) 2
• Hemofiltration clearance contributes approximately 22.0 ± 4.7 mL/min to total clearance 3
• Approximately 47% of the administered dose is removed through CVVH during a 12-hour dosing interval 3

Critical Dosing Variables

• Residual diuresis is the most important modifier of meropenem clearance in CRRT patients, with clearance calculated as: CL = 3.68 + 0.22 × (residual diuresis/100) 1
• CRRT intensity (dialysate/ultrafiltrate flow rates) was NOT identified as a significant clearance modifier in the most recent population pharmacokinetic study 1
• Patient type matters: septic patients have lower volume of distribution (15.7 L) compared to polytraumatized patients (69.5 L) 4

Extended Infusion Strategy

When to Use Extended Infusion

• Extended infusion (3 hours) is recommended for patients with preserved residual diuresis to maintain adequate time above MIC 1
• The French Society of Pharmacology and Therapeutics recommends extended infusion for beta-lactams in critically ill patients to optimize pharmacodynamic targets 5
• Extended infusion is particularly important when treating organisms with MIC ≥8 mg/L 6

Continuous Infusion Alternative

• Continuous infusion is recommended for septic patients and polytraumatized patients when treating pathogens with MIC ≥4 mg/L 4
• Computer simulations demonstrate that intermittent dosing may not achieve adequate efficacy indices in these populations 4

Dosing for Resistant Organisms

High MIC Pathogens (MIC ≥8 mg/L)

• Do NOT use standard meropenem dosing for polytraumatized patients with MIC ≥8 mg/L, as excessive doses would be required 4
• For carbapenem-resistant organisms with high MIC, consider meropenem-vaborbactam or alternative agents 6
• If meropenem must be used for MIC ≥8 mg/L, administer 2 grams every 8 hours as a 3-hour extended infusion 6

Common Pitfalls to Avoid

Underdosing Risk

• The most common error is underdosing due to conflicting literature recommendations 2
• Standard renal failure dosing (500 mg every 12 hours) is INSUFFICIENT for CRRT patients due to significant drug removal by hemofiltration 3
• The recommended dose should be increased by 100% compared to anuric patients NOT on CRRT 3

Overlooking Residual Renal Function

• Failure to account for residual diuresis leads to subtherapeutic concentrations in patients with preserved urine output 1
• Measure 24-hour urine output to guide dosing decisions: <100 mL/24h = oligoanuric dosing; >100 mL/24h = preserved diuresis dosing 1

CRRT Intensity Misconception

• Do NOT adjust meropenem dose based on CRRT flow rates alone, as this was not a significant predictor of clearance in the most robust pharmacokinetic study 1
• Focus instead on residual diuresis and patient type (septic vs. polytraumatized) 1

Monitoring and Adjustment

Therapeutic Drug Monitoring

• The French guidelines suggest performing beta-lactam TDM 24-48 hours after treatment initiation and after any significant clinical change 5
• Target trough concentrations: 7.3 ± 1.3 mg/L for every 12-hour dosing, or 11.9 ± 0.7 mg/L for every 8-hour dosing 3
• For continuous infusion, target steady-state concentrations 4-5 times the MIC 5

Clinical Response Assessment

• Reassess dosing if residual renal function changes significantly during CRRT 5
• Consider dose escalation if clinical response is inadequate after 48-72 hours despite source control 5