What is the recommended dosing of Meropenem (generic name) for a patient undergoing Continuous Veno-Venous Hemofiltration (CVVH) with Impaired renal function?

From the Guidelines

For patients on continuous venovenous hemofiltration (CVVH), meropenem should be dosed at 1 gram every 8 hours to ensure adequate antimicrobial coverage, considering the altered drug clearance in these patients. This recommendation is based on the principles outlined in the guidelines from the French Society of Pharmacology and Therapeutics and the French Society of Anaesthesia and Intensive Care Medicine 1. The incidence of acute kidney injury (AKI) in ICU patients is significant, with about 40% requiring renal replacement therapy (RRT), which can cause considerable changes in antibiotic pharmacokinetics (PK) 1.

Given the complexity of antibiotic elimination during RRT, with factors such as the type of RRT technique, flow rates, and the physicochemical properties of the molecule influencing drug clearance, personalized therapeutic drug monitoring (TDM) is suggested for critical care patients undergoing RRT 1. However, in the absence of TDM, dosing adjustments based on clinical response and residual renal function are crucial. Meropenem's relatively low protein binding and molecular weight allow it to be moderately removed by CVVH, but its volume of distribution is increased in critically ill patients, which can affect drug concentrations.

Key considerations for meropenem dosing in CVVH include:

• The technique of RRT used, with CVVHDF potentially leading to faster elimination of some beta-lactams compared to CVVH 1.
• The impact of dialysis flow-rate on antibiotic elimination, with higher flow rates potentially increasing clearance 1.
• The role of residual renal function, which can significantly contribute to the clearance of beta-lactam antibiotics, including meropenem 1.
• The potential for hypoalbuminemia to affect beta-lactam elimination, although the pharmacodynamic impact may be minimal 1.

In clinical practice, monitoring clinical response and considering therapeutic drug monitoring if available is essential, especially in patients with fluctuating kidney function or those not responding appropriately to therapy 1. Dosing regimens may need to be adjusted based on these factors to ensure effective treatment while minimizing the risk of toxicity.

From the FDA Drug Label

There is inadequate information regarding the use of meropenem for injection in patients on hemodialysis or peritoneal dialysis.

The FDA drug label does not answer the question.

From the Research

Meropenem Dosing on CVVH

• The pharmacokinetics of meropenem in patients undergoing continuous venovenous hemofiltration (CVVH) have been studied to determine the appropriate dosing regimen 2, 3, 4, 5.
• A study published in 1998 found that the total body clearance and elimination half-life of meropenem in patients undergoing CVVH were 143.7 +/- 18.6 ml/min and 2.46 +/- 0.41 h, respectively, and recommended a dosing regimen of 1 g every 8 h 2.
• Another study published in 2005 used Monte Carlo simulation to calculate the bactericidal target attainment for various dosing regimens of meropenem against Pseudomonas aeruginosa and Acinetobacter species, and found that a regimen of 1,000 mg every 8 h achieved 100% target attainment at the breakpoint of 4 microg/ml 3.
• A literature review published in 2021 found that the daily dose of meropenem commonly ranged from 3 to 6 g/day, and that therapeutic drug monitoring (TDM) can help to maximize the clinical outcomes of treatment with meropenem 6.
• A study published in 2022 found that burn injury and CVVH can affect the pharmacokinetics of meropenem, and recommended a standard dose of 1000 mg every 8 hours, with the option to adjust the dose based on the severity of illness and the presence of augmented renal clearance (ARC) 4.
• Another study published in 2010 found that high-volume CVVHF causes significant clearance of meropenem, necessitating steady-state doses of 1,000 mg every 8 h to maintain sufficient concentrations to treat less susceptible organisms such as Burkholderia pseudomallei 5.

Key Findings

• The recommended dosing regimen for meropenem in patients undergoing CVVH is 1,000 mg every 8 h 2, 3, 4, 5.
• TDM can help to maximize the clinical outcomes of treatment with meropenem 6.
• Burn injury and CVVH can affect the pharmacokinetics of meropenem, and may require dose adjustments 4.
• High-volume CVVHF causes significant clearance of meropenem, necessitating higher doses to maintain sufficient concentrations 5.