Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically...

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Critical Care Medicine
• Antimicrobial Stewardship

Background:

• Vancomycin is a cornerstone for empirical antimicrobial therapy in critically ill sepsis patients.
• Continuous infusion (CI) offers potential for stable vancomycin exposure, but optimal dosing strategies are complex.
• Accurate vancomycin dosing is essential to maximize efficacy and minimize toxicity in intensive care unit (ICU) settings.

Purpose of the Study:

• To conduct a population pharmacokinetic (PK) analysis of vancomycin administered via CI in ICU patients.
• To identify optimal vancomycin loading and maintenance doses for various renal function levels, including those on continuous renal replacement therapy (CRRT).
• To establish target vancomycin exposure levels (AUC24-48 h) for improved therapeutic outcomes.

Main Methods:

• Population PK modeling was performed on data from ICU patients receiving vancomycin CI.
• The model was externally validated using data from a separate center.
• Simulations were used to determine optimal dosing regimens based on estimated creatinine clearance (CRCL) and CRRT status.

Main Results:

• A two-compartment PK model effectively described vancomycin disposition.
• Vancomycin clearance was significantly influenced by CRRT and CRCL.
• Simulations suggested a loading dose of 27.5 mg/kg IBW and maintenance doses ranging from 17.5 to 30 mg/kg IBW, achieving target AUC in 55.8% of simulated patients.

Conclusions:

• A validated PK model for vancomycin CI in ICU patients, including those on CRRT, has been developed.
• This model-informed precision dosing approach facilitates early optimization of vancomycin exposure.
• Implementing these optimized dosing strategies can enhance vancomycin therapeutic efficacy in critically ill patients.