Meropenem Dosing in Adults with Impaired Renal Function
For adults with renal impairment, maintain the full 1 gram dose of meropenem when treating serious infections and extend the dosing interval rather than reducing individual doses, with specific adjustments based on creatinine clearance. 1, 2
Standard Dose Adjustment Algorithm by Creatinine Clearance
The FDA-approved dosing adjustments for renal impairment are structured as follows 2:
- CrCl >50 mL/min: Full recommended dose (500 mg for cSSSI, 1 gram for intra-abdominal infections) every 8 hours
- CrCl 26-50 mL/min: Full recommended dose every 12 hours
- CrCl 10-25 mL/min: One-half recommended dose every 12 hours
- CrCl <10 mL/min: One-half recommended dose every 24 hours
Critical Principle: Maintain Dose Magnitude, Extend Interval
The Infectious Diseases Society of America specifically advises against reducing individual doses below 1 gram when treating serious infections, even in renal impairment. 1 This recommendation takes advantage of meropenem's concentration-dependent bactericidal effect. 1 The half-life of meropenem increases significantly with declining renal function (from approximately 1 hour in normal function to prolonged elimination in impairment), which supports extending dosing intervals while maintaining dose magnitude. 1, 3
Special Populations Requiring Modified Approaches
Hemodialysis Patients
- Approximately 50% of meropenem is eliminated by intermittent hemodialysis. 4
- Always administer doses after dialysis sessions to avoid premature drug removal and subtherapeutic levels. 4
- The Clinical Infectious Diseases journal specifically warns against pre-dialysis administration, as this leads to premature drug removal. 4
Sustained Low-Efficiency Dialysis (SLED)
- Maintain the full 1 gram dose every 12 hours rather than reducing individual doses. 1, 4
- The National Kidney Foundation supports this approach to preserve concentration-dependent killing. 4
Continuous Renal Replacement Therapy (CRRT)
- Administer 1 gram every 8 hours to compensate for continuous drug removal. 4
- CRRT removes 25-50% of meropenem, while CVVHDF removes 13-53%, necessitating higher doses than standard renal impairment adjustments. 4, 5
- The elimination half-life during CRRT is approximately 2.5-8.7 hours. 4
Dosing for Resistant Organisms in Renal Impairment
When treating infections with organisms having MIC ≥4-8 mg/L, use extended infusion over 3 hours, even in renal impairment. 4 This optimizes pharmacokinetic/pharmacodynamic properties by maximizing the time that free drug concentrations remain above the MIC. 4
For carbapenem-resistant Enterobacterales with meropenem MIC ≥8 mg/L, the European Society of Clinical Microbiology and Infectious Diseases specifically recommends extended 3-hour infusion of 1 gram every 8 hours. 4
Therapeutic Drug Monitoring and Safety
Target Concentrations
- Maintain trough concentrations below 64 mg/L to prevent neurological toxicity, particularly in critically ill patients with renal impairment. 1, 4
- The Society of Critical Care Medicine recommends therapeutic drug monitoring for patients on renal replacement therapy and those with expected pharmacokinetic variability. 4
Neurological Safety
- Meropenem has lower pro-convulsive activity compared to imipenem, making it safer in renal dysfunction. 4
- However, neurological toxicity typically occurs when trough concentrations exceed 64 mg/L. 4
- Monitor renal function indicators throughout treatment. 4
Common Pitfalls to Avoid
- Never reduce individual doses below 1 gram for serious infections in renal impairment; instead extend the dosing interval. 1
- Never administer meropenem before dialysis sessions in hemodialysis patients, as this causes premature drug removal. 4
- Do not underdose patients on CRRT by using standard renal impairment adjustments; these patients require higher doses (1 gram every 8 hours) due to continuous drug removal. 4
- Consider therapeutic drug monitoring in critically ill patients with renal impairment to ensure adequate exposure while avoiding toxicity. 4