Meropenem Dosing in Adults
Standard Dosing for Normal Renal Function
For adults with normal renal function, administer meropenem 1 gram intravenously every 8 hours by infusion over 15-30 minutes for most serious infections, including intra-abdominal infections and infections caused by Pseudomonas aeruginosa. 1
- For complicated skin and skin structure infections (cSSSI) not involving Pseudomonas, a reduced dose of 500 mg every 8 hours may be used 1
- Extended infusion over 3 hours is recommended when treating resistant organisms with MIC ≥8 mg/L to optimize time above MIC 2, 3
- Critically ill ICU patients with preserved renal function often require higher doses due to increased drug clearance and altered pharmacokinetics 3
Administration Methods
- Standard infusion: 15-30 minutes 1
- Bolus injection: 3-5 minutes (5-20 mL) 1
- Extended infusion: 3 hours for resistant pathogens 2, 3
Dosing Adjustments for Renal Impairment
Dosage reduction is mandatory in patients with creatinine clearance <50 mL/min, following a structured algorithm based on renal function. 1
Renal Impairment Dosing Algorithm
| Creatinine Clearance (mL/min) | Dose | Interval |
|---|---|---|
| >50 | Full dose (500 mg or 1 g) | Every 8 hours |
| 26-50 | Full dose (500 mg or 1 g) | Every 12 hours |
| 10-25 | Half dose (250 mg or 500 mg) | Every 12 hours |
| <10 | Half dose (250 mg or 500 mg) | Every 24 hours |
Critical Considerations for Renal Dosing
- Maintain the full 1 gram dose and extend the interval to every 12 hours in moderate renal impairment, rather than reducing individual doses to 500 mg every 8 hours, to preserve peak concentrations needed for optimal bacterial killing 2
- The elimination half-life increases from approximately 1 hour in healthy volunteers to up to 13.7 hours in anuric patients 4
- Approximately 50% of meropenem is removed by intermittent hemodialysis 2, 4
- Administer doses after dialysis sessions to prevent premature drug removal and ensure adequate exposure 2
Special Populations Requiring Modified Dosing
Intermittent Hemodialysis (IHD)
- Administer the full 1 gram dose every 12 hours, with doses given after dialysis sessions 2
- Approximately 50% of the drug is eliminated during each dialysis session 2, 4
- Post-dialysis administration is critical to avoid subtherapeutic levels 2
Continuous Renal Replacement Therapy (CRRT)
- Administer 1 gram every 8 hours to compensate for continuous drug removal 2
- CRRT removes 25-50% of meropenem, while CVVHDF removes 13-53% 2, 4
- The elimination half-life during CRRT is approximately 2.5-8.7 hours 2
- Therapeutic drug monitoring is strongly recommended for all patients on CRRT to ensure adequate exposure 2, 3
- Residual diuresis significantly impacts total drug clearance and should be considered 2
Sustained Low-Efficiency Dialysis (SLED)
- Maintain the full 1 gram dose with a dosing interval of every 12 hours 2
- Do not reduce individual doses below 1 gram, as smaller doses may compromise efficacy despite renal impairment 2
Treatment of Resistant Organisms
When treating infections with organisms having MIC ≥8 mg/L, use extended 3-hour infusion of 1 gram every 8 hours, even in patients with renal impairment. 2
- This approach optimizes pharmacokinetic/pharmacodynamic properties by maximizing time above MIC 2, 3
- For carbapenem-resistant Enterobacterales, extended infusion is specifically recommended 2, 3
- Standard renal dosing adjustments may need modification when treating highly resistant pathogens 2
Therapeutic Drug Monitoring and Safety
When to Monitor
- All patients on CRRT or renal replacement therapy 2, 3
- ICU patients with clinical signs of potential toxicity 3
- Patients with expected pharmacokinetic variability 3
Toxicity Thresholds
- Neurological toxicity typically occurs when trough concentrations exceed 64 mg/L 2, 3
- Meropenem has lower pro-convulsive activity compared to imipenem, making it safer in renal dysfunction 2
- Seizures are rare (0.1%), even in renally impaired patients 5
- Meropenem does not cause clinically significant changes in renal function indicators 2, 5
Common Pitfalls to Avoid
- Never administer meropenem before dialysis sessions, as this leads to premature drug removal and subtherapeutic levels 2
- Avoid reducing individual doses below 1 gram in patients requiring treatment for serious infections, even with renal impairment—instead, extend the dosing interval 2
- Underdosing is common in ICU patients with normal renal function due to increased clearance; consider higher doses at treatment onset 3
- When using continuous infusion, prepare new infusion bags every 6 hours due to limited stability at room temperature (6-12 hours) 2, 3
- Large inter- and intra-patient variability in meropenem concentrations occurs in critically ill patients, making therapeutic drug monitoring valuable 6