Meropenem Dosing with SLED (Sustained Low-Efficiency Dialysis)
For patients on SLED, administer meropenem 1 gram every 12 hours, given after each dialysis session to avoid premature drug removal. 1
Dosing Algorithm for SLED
Standard SLED Dosing
- Administer 1 gram IV every 12 hours as the primary dosing regimen for patients undergoing SLED 1, 2
- Time the dose immediately after dialysis sessions to prevent premature removal of the drug and facilitate directly observed therapy 1
- Maintain the full 1 gram dose (do not reduce to 500 mg) to take advantage of meropenem's concentration-dependent bactericidal effect 3
Pharmacokinetic Rationale
- SLED removes approximately 25-50% of meropenem, similar to continuous renal replacement therapy (CRRT) 1
- Approximately 50% of meropenem is eliminated by intermittent hemodialysis, making post-dialysis dosing critical 1
- The elimination half-life is prolonged in renal impairment (up to 6.1 hours compared to 1 hour in normal function), supporting the every 12-hour interval 4, 5
Administration Method
Infusion Technique
- Administer as a 30-minute IV infusion for the 1 gram dose 2
- Extended infusion over 3 hours may be considered for resistant organisms with MIC ≥ 8 mg/L, though this is less commonly needed in SLED patients 6
- Bolus injection (over 3-5 minutes) is an alternative for the 1 gram dose but should be used cautiously 2
Therapeutic Drug Monitoring (TDM)
When to Monitor
- TDM is strongly recommended for all patients on renal replacement therapy including SLED 6, 1
- Monitor trough concentrations to ensure adequate exposure while avoiding toxicity 6
- Target trough concentrations should remain above the MIC of the suspected pathogen but below 64 mg/L to prevent neurological toxicity 6, 1
Toxicity Thresholds
- Neurological toxicity occurs when trough concentrations exceed 64 mg/L 6, 1
- Meropenem has lower pro-convulsive activity compared to imipenem, making it safer in renal dysfunction 1
- When free trough concentration normalized to the EUCAST clinical breakpoint exceeds 8, neurological deterioration may occur in approximately two-thirds of ICU patients 6
Critical Pitfalls to Avoid
Common Dosing Errors
- Do not reduce the individual dose below 1 gram - smaller doses may reduce efficacy despite renal impairment 3
- Never administer before dialysis - this results in premature drug removal and subtherapeutic levels 1
- Do not use the standard renal impairment dosing table from the FDA label (which recommends 500 mg every 12-24 hours for CrCl 10-25 mL/min) as SLED provides more clearance than native kidneys at this level 2
Special Considerations
- For infections with Pseudomonas aeruginosa or other resistant organisms, maintain the 1 gram dose and consider TDM to ensure adequate exposure 2, 7
- Hyperbolic relationship exists between creatinine clearance and meropenem concentrations - SLED patients fall into the range requiring careful monitoring 7
- Standard dosing results in insufficient exposure in a considerable fraction of critically ill patients, making post-dialysis timing even more critical 7
Treatment Duration
- For bloodstream infections: 7-14 days 6
- For complicated urinary tract infections: 5-7 days 6
- For complicated intra-abdominal infections: 5-7 days 6
- Individualize based on infection site, source control, and clinical response 6
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