What is the appropriate dosing for Meropenem (Meropeneum) in patients with Impaired renal function?

From the Guidelines

Meropenem is typically dosed at 1 gram intravenously every 8 hours for most serious infections in adults with normal renal function. For meningitis or severe infections caused by less susceptible organisms, the dose may be increased to 2 grams every 8 hours 1. Dose adjustments are required for patients with renal impairment. The most recent and highest quality study provides guidance on dosing for patients with normal renal function, but for renal impairment, adjustments are necessary: for creatinine clearance 26-50 mL/min, give 1 gram every 12 hours; for clearance 10-25 mL/min, give 500 mg every 12 hours; and for clearance less than 10 mL/min, give 500 mg every 24 hours.

Key Considerations

• Meropenem should be infused over 15-30 minutes for standard administration, though extended infusions of 3 hours may be beneficial for less susceptible organisms to maximize time above MIC.
• The typical treatment duration ranges from 7-14 days depending on the infection site and severity.
• Meropenem is a carbapenem antibiotic that works by inhibiting bacterial cell wall synthesis and is effective against a broad spectrum of gram-positive, gram-negative, and anaerobic bacteria, including many multidrug-resistant organisms.

Important Details

• It penetrates well into most body tissues and fluids, including the cerebrospinal fluid, making it suitable for treating central nervous system infections.
• For children, the standard dose is 20-40 mg/kg every 8 hours, not exceeding the adult dose.
• Initial antibiotic therapy should be adjusted or streamlined on the basis of microbiologic data and clinical response to therapy 1.

Renal Impairment

• Dose adjustments for renal impairment are crucial to avoid toxicity and ensure efficacy.
• The provided evidence does not directly address meropenem dosing in renal impairment, but general principles of antibiotic dosing in renal impairment suggest the need for careful adjustment based on creatinine clearance 1.

From the FDA Drug Label

2.1 Adult Patients The recommended dose of meropenem for injection is 500 mg given every 8 hours for skin and skin structure infections and 1 gram given every 8 hours for intra-abdominal infections. When treating complicated skin and skin structure infections caused by P. aeruginosa, a dose of 1 gram every 8 hours is recommended Meropenem for injection should be administered by intravenous infusion over approximately 15 minutes to 30 minutes. Doses of 1 gram may also be administered as an intravenous bolus injection (5 mL to 20 mL) over approximately 3 minutes to 5 minutes.

The recommended meropenem dosing is as follows:

• For skin and skin structure infections: 500 mg every 8 hours
• For intra-abdominal infections: 1 gram every 8 hours
• For complicated skin and skin structure infections caused by P. aeruginosa: 1 gram every 8 hours Administration can be via intravenous infusion over 15-30 minutes or intravenous bolus injection over 3-5 minutes 2

From the Research

Meropenem Dosing

• The daily dosages of meropenem may range from 0.5 to 1 g every 6 to 8 hours in patients with normal renal function 3.
• The daily dose of meropenem can be safely increased to 6 g 3.
• Meropenem is approved for use in various serious infections, including complicated intra-abdominal infection, complicated skin and skin structure infection, and bacterial meningitis 4.
• The recommended dosing interval for meropenem is every 8 hours 4.

Pharmacokinetics and Pharmacodynamics

• There is extensive pharmacokinetic variability in critically ill patients receiving meropenem, and a large proportion of patients may not achieve the desired pharmacokinetic/pharmacodynamic target 5.
• High creatinine clearance is an independent predictor of not achieving the pharmacokinetic/pharmacodynamic target 5.
• Alternative administration methods, such as extended infusions, may not be sufficient to achieve the desired pharmacokinetic/pharmacodynamic target in patients with augmented renal clearance 5.

Comparative Studies

• Meropenem has similar efficacy to comparator antibacterial agents, including imipenem/cilastatin, clindamycin, and cefotaxime, in various infections 4.
• Piperacillin-tazobactam may be a suitable alternative to meropenem in some cases, but it may lead to more microbiological failures 6.
• Definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality in patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance 7.