What is the recommended dose and frequency of meropenem for patients with normal and impaired renal function?

Meropenem Dosing Recommendations for Normal and Impaired Renal Function

For patients with normal renal function, meropenem should be administered at 1 gram every 8 hours, while patients with renal impairment require dose adjustments based on creatinine clearance. 1, 2

Standard Dosing for Normal Renal Function

• For most serious infections including intra-abdominal infections in critically ill patients, the recommended dose is 1 gram every 8 hours 2, 1
• For complicated skin and skin structure infections, a lower dose of 500 mg every 8 hours may be sufficient 1
• When treating infections caused by Pseudomonas aeruginosa or other resistant organisms, 1 gram every 8 hours is recommended 1, 2
• Extended infusion over 3 hours is beneficial for optimizing pharmacokinetic/pharmacodynamic properties when treating resistant organisms with higher MICs 2

Dosing for Impaired Renal Function

• A loading dose of 1-2g should be administered before starting continuous infusion, even in patients with renal impairment, to quickly achieve therapeutic concentrations 3, 1
• Subsequent dosing should be adjusted based on creatinine clearance 1:
  • CrCl >50 mL/min: Full recommended dose every 8 hours
  • CrCl 26-50 mL/min: Full recommended dose every 12 hours
  • CrCl 10-25 mL/min: Half recommended dose every 12 hours
  • CrCl <10 mL/min: Half recommended dose every 24 hours 1

Administration Methods

• Standard administration: Intravenous infusion over 15 to 30 minutes 1
• Bolus injection: Can be given over 3-5 minutes (5-20 mL) 1
• Extended infusion: 3-hour infusion is recommended for resistant organisms with higher MICs 2
• Continuous infusion: May be used but requires consideration of meropenem's limited stability at room temperature (typically requiring preparation of new infusion bags every 6 hours) 3, 4

Special Considerations for Renal Replacement Therapy

• Therapeutic drug monitoring (TDM) is strongly recommended for patients undergoing renal replacement therapy 4, 3
• For patients on continuous venovenous hemofiltration (CVVH), dosing may need to be increased by approximately 100% compared to standard dosing for anuric patients without CVVH 5, 6
• Approximately 13-53% of meropenem is eliminated by continuous venovenous hemodiafiltration (CVVHDF), requiring dose adjustments based on the specific renal replacement modality 3

Monitoring Recommendations

• Therapeutic drug monitoring should be performed in ICU patients with expected pharmacokinetic variability or clinical signs of toxicity 4, 7
• TDM should be conducted 24-48 hours after treatment initiation, with target plasma concentration maintained above the MIC of the suspected pathogen 3
• Monitor for potential neurological adverse effects (seizures) with excessive plasma concentrations, particularly in patients with CNS infections or severe renal impairment 3

Pediatric Dosing

• For children 3 months and older with normal renal function 1:
  • Complicated skin and skin structure infections: 10 mg/kg (up to 500 mg) every 8 hours
  • Intra-abdominal infections: 20 mg/kg (up to 1 gram) every 8 hours
  • Meningitis: 40 mg/kg (up to 2 grams) every 8 hours 1

Meropenem's pharmacokinetic profile shows a volume of distribution of approximately 21L, indicating predominantly extracellular distribution, with an elimination half-life of approximately 1 hour in patients with normal renal function 8. This half-life is significantly prolonged in patients with renal impairment, necessitating the dose adjustments outlined above 8, 5.