What is the recommended dose of meropenem for patients with varying degrees of renal function and infection severity?

From the Guidelines

Meropenem dosing should be adjusted based on both renal function and infection severity, with a standard dose of 1 gram every 8 hours for most serious infections in patients with normal renal function (creatinine clearance >50 mL/min) 1. For patients with varying degrees of renal function, the following dose adjustments are recommended:

• Normal renal function (creatinine clearance >50 mL/min): 1 gram every 8 hours
• Moderate renal impairment (creatinine clearance 26-50 mL/min): 1 gram every 12 hours
• Severe renal impairment (creatinine clearance 10-25 mL/min): 500 mg every 12 hours
• End-stage renal disease (creatinine clearance <10 mL/min): 500 mg every 24 hours Patients on hemodialysis should receive a supplemental dose after dialysis sessions. Meropenem requires dose adjustment in renal impairment because it is primarily eliminated by the kidneys, with approximately 70% excreted unchanged in urine 1. The drug has time-dependent bactericidal activity, so maintaining adequate blood levels between doses is crucial for efficacy. Infusion time should be at least 30 minutes for standard dosing, though extended infusions of 3 hours may be beneficial for certain resistant organisms by maximizing the time drug concentrations remain above the minimum inhibitory concentration. It's worth noting that the most recent and highest quality study 1 provides the basis for these recommendations, and dose adjustment is critical to minimize the risk of toxicity and ensure optimal efficacy in patients with renal impairment. In addition, the guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia also support the use of meropenem as an effective treatment option 1. However, the primary consideration for meropenem dosing should be based on the patient's renal function and infection severity, as outlined in the most recent guidelines 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION 500 mg every 8 hours by intravenous infusion over 15 to 30 minutes for complicated skin and skin structure infections (cSSSI) for adult patients. When treating infections caused by Pseudomonas aeruginosa, a dose of 1 gram every 8 hours is recommended. (2. 1) 1 gram every 8 hours by intravenous infusion over 15 minutes to 30 minutes for intra-abdominal infections for adult patients. (2.1) Recommended meropenem for injection Dosage Schedule for Adult Patients with Renal Impairment Creatinine Clearance (mL/min) Dose (2) (dependent on type of infection) (2) Dosing Interval Greater than 50Recommended dose (500 mg cSSSI and 1 gram Intra-abdominal)Every 8 hours 26 to 50Recommended doseEvery 12 hours 10 to 25One-half recommended doseEvery 12 hours Less than 10One-half recommended doseEvery 24 hours

The recommended dose of meropenem for patients with varying degrees of renal function and infection severity is as follows:

• For adult patients with normal renal function (creatinine clearance > 50 mL/min), the recommended dose is:
  • 500 mg every 8 hours for complicated skin and skin structure infections (cSSSI)
  • 1 gram every 8 hours for intra-abdominal infections and when treating infections caused by Pseudomonas aeruginosa
• For adult patients with renal impairment, the dose should be reduced as follows:
  • Creatinine clearance 26-50 mL/min: recommended dose every 12 hours
  • Creatinine clearance 10-25 mL/min: one-half recommended dose every 12 hours
  • Creatinine clearance < 10 mL/min: one-half recommended dose every 24 hours
• For pediatric patients 3 months of age and older with normal renal function, the recommended dose is:
  • 10-20 mg/kg (up to a maximum dose of 500 mg) every 8 hours for cSSSI
  • 20 mg/kg (up to a maximum dose of 1 gram) every 8 hours for intra-abdominal infections
  • 40 mg/kg (up to a maximum dose of 2 grams) every 8 hours for meningitis 2

From the Research

Meropenem Dosing Recommendations

The recommended dose of meropenem varies depending on the patient's renal function and infection severity.

• For patients with normal renal function, a dose of 1 g every 8 hours is commonly used 3.
• However, some studies suggest that a dose of 500 mg every 6 hours may be equally effective and potentially more cost-effective 3.
• For patients with renal impairment, the dose of meropenem should be adjusted based on the patient's creatinine clearance.
• A study found that a dose of 2 g/24 hours achieved a probability of target attainment of 95% in patients with renal replacement therapy 4.
• In patients without renal replacement therapy, a dose of 3 g/24 hours or prolonged infusion of 1 g meropenem over 8 hours may be necessary to achieve adequate drug concentrations 4.

Continuous vs Intermittent Administration

• Continuous infusion of meropenem has been shown to provide better pharmacodynamic efficacy and shorter treatment duration compared to intermittent administration 5.
• However, a randomized clinical trial found no significant difference in clinical outcomes between continuous and intermittent administration of meropenem in critically ill patients with sepsis 6.
• The choice of administration method may depend on individual patient factors and the specific clinical scenario.

Special Considerations

• Augmented renal clearance can lead to subtherapeutic concentrations of meropenem, even at recommended doses 7.
• In such cases, higher doses of meropenem may be necessary to achieve adequate drug concentrations.
• Close monitoring of drug concentrations and renal function is essential to ensure effective treatment and minimize the risk of adverse effects.