What are the recommended meropenem dosing regimens for an adult patient based on creatinine clearance levels (≥50, 30‑49, 10‑29, <10 mL/min) and dialysis status (intermittent hemodialysis or continuous renal replacement therapy)?

Meropenem Renal Dosing in Adults

For adults with renal impairment, reduce meropenem dosing based on creatinine clearance: maintain the full dose (500 mg or 1 g depending on infection type) but extend the interval to every 12 hours for CrCl 26-50 mL/min, reduce to half-dose every 12 hours for CrCl 10-25 mL/min, and half-dose every 24 hours for CrCl <10 mL/min. 1

Standard Dosing Adjustments by Creatinine Clearance

The FDA-approved dosing algorithm is straightforward and based on measured or estimated creatinine clearance 1:

• CrCl >50 mL/min: Standard dosing—500 mg every 8 hours for complicated skin/soft tissue infections (cSSSI) or 1 gram every 8 hours for intra-abdominal infections 1

• CrCl 26-50 mL/min: Maintain full dose (500 mg or 1 g) but extend interval to every 12 hours 1

• CrCl 10-25 mL/min: Reduce to half the recommended dose every 12 hours 1

• CrCl <10 mL/min: Reduce to half the recommended dose every 24 hours 1

The critical principle here is that for moderate impairment (CrCl 26-50), you preserve the individual dose strength to maintain adequate peak concentrations needed for meropenem's concentration-dependent killing, while extending the interval 2. Only in severe impairment do you reduce the actual dose 1.

Intermittent Hemodialysis Dosing

The FDA label states there is inadequate information for specific dosing recommendations in hemodialysis patients 1. However, clinical guidance fills this gap:

• Approximately 50% of meropenem is removed by a single hemodialysis session 2, 3

• Administer doses immediately after dialysis sessions to prevent premature drug removal and ensure adequate therapeutic levels 2

• A practical regimen is 500 mg after each dialysis session (typically three times weekly for patients on standard intermittent hemodialysis schedules) 2

• Never administer before dialysis, as this leads to subtherapeutic levels and treatment failure 2

The half-life of meropenem is prolonged up to 13.7 hours in anuric patients with end-stage renal disease, compared to approximately 1 hour in healthy volunteers 3.

Continuous Renal Replacement Therapy (CRRT)

For patients on CRRT, use 1 gram every 8 hours to compensate for continuous drug removal 2. This recommendation differs substantially from standard renal impairment dosing because:

• CRRT removes 25-50% of meropenem during continuous venovenous hemofiltration (CVVHF) 3, 4

• Continuous venovenous hemodiafiltration (CVVHDF) removes 13-53% of the drug 3, 5

• The elimination half-life during CRRT is approximately 2.5-8.7 hours 2, 4

• Total meropenem clearance during CVVHF averages 52 mL/min, with hemofiltration clearance contributing 22 mL/min 4

Residual diuresis is a critical but often overlooked factor 6. Patients with preserved residual creatinine clearance >50 mL/min show substantially higher drug clearance compared to oligoanuric patients (<10 mL/min), potentially requiring dose adjustments beyond standard CRRT recommendations 6.

CRRT Dosing Nuances

For standard susceptible organisms (MIC ≤2 mg/L):

• Oligoanuric patients: 500 mg every 8 hours as 30-minute infusion 6
• Patients with preserved diuresis: 500 mg every 8 hours as 3-hour extended infusion 6

For resistant organisms (MIC 2-4 mg/L):

• Oligoanuric patients: 500 mg every 6 hours as 30-minute infusion 6
• Patients with preserved diuresis: 500 mg every 6 hours as 3-hour extended infusion 6

Sustained Low-Efficiency Dialysis (SLED)

For SLED, maintain the full 1 gram dose every 12 hours 2. The key principles are:

• Do not reduce the individual dose below 1 gram, as smaller doses compromise efficacy despite renal impairment 2
• The 12-hour interval is supported by the prolonged elimination half-life in renal impairment 2
• This preserves concentration-dependent bactericidal activity 2

Critical Safety Considerations

Therapeutic Drug Monitoring

Consider therapeutic drug monitoring in critically ill patients with renal impairment to ensure adequate drug exposure 2. This is particularly important for:

• Patients on any form of renal replacement therapy 2
• Treatment of resistant organisms with elevated MICs 2
• Critically ill patients with unpredictable pharmacokinetics 7

Neurological Toxicity

Neurological toxicity typically occurs when trough concentrations exceed 64 mg/L 2. Meropenem has lower pro-convulsive activity compared to imipenem, making it safer in renal dysfunction 2, but accumulation still poses risk with inadequate dose adjustment.

Augmented Renal Clearance

A common pitfall: Patients with CrCl ≥90 mL/min may require increased dosing (up to 6 g/day) or continuous infusion to achieve adequate MIC coverage 7. Standard dosing is often suboptimal in ICU patients with normal or augmented renal clearance 7.

Extended Infusion for Resistant Organisms

When treating infections with organisms having MIC ≥4-8 mg/L, use extended 3-hour infusion even in renal impairment 2. For carbapenem-resistant Enterobacterales with meropenem MIC ≥8 mg/L, specifically use 1 gram every 8 hours as a 3-hour infusion 2. This optimizes the time that free drug concentrations remain above the MIC, which is the critical pharmacokinetic/pharmacodynamic parameter for beta-lactam efficacy 2.