Vancomycin dosing in high-intensity continuous renal replacement therapy: A retrospective cohort study

Area of Science:

• Pharmacokinetics
• Critical Care Medicine
• Nephrology

Background:

• Vancomycin serum concentrations inversely correlate with continuous renal replacement therapy (CRRT) intensity, specifically dialysate flow rate (DFR).
• Optimal vancomycin dosing in high-intensity CRRT (DFR >30 mL/kg/h) lacks robust evidence.
• Shift from trough-based to area under the curve (AUC)-based vancomycin dosing necessitates understanding CRRT's impact on AUC/MIC targets.

Purpose of the Study:

• Evaluate vancomycin dosing strategies in patients undergoing high-intensity CRRT.
• Assess the achievement of pharmacokinetic targets with current dosing regimens.
• Determine optimal vancomycin dosage for achieving target AUC/MIC ratios in this population.

Main Methods:

• Retrospective cohort study of adult patients on high-intensity CRRT receiving vancomycin.
• High-intensity CRRT defined as DFR ≥3 L/h and >30 mL/kg/h.
• Patients stratified into traditional (15 mg/kg/day) and enhanced (≥15 mg/kg/day) vancomycin dosing groups.
• Primary outcome: percentage of patients achieving steady-state AUC24/MIC ≥400 mg*h/L at first vancomycin level.

Main Results:

• Enhanced dosing group achieved primary endpoint more frequently (74%) than the traditional group (54%) (p=0.029).
• Higher rates of therapeutic vancomycin trough levels (10-20 μg/mL) observed in the enhanced group (66.7% vs. 45%, p=0.013).
• Increasing DFR correlated with the need for higher vancomycin doses (up to 27 mg/kg/day) to reach therapeutic targets.

Conclusions:

• This study is the first to examine CRRT intensity's effect on vancomycin AUC/MIC.
• Vancomycin doses of ≥15 mg/kg/day are recommended for achieving early therapeutic targets in patients on high-intensity CRRT.
• Enhanced vancomycin dosing strategies are crucial for optimizing efficacy and safety in this patient group.