Factors influencing vancomycin loading dose for hospitalized hemodialysis patients: Prospective observational cohort study

Abstract

Background: The increasing use of vancomycin to treat methicillin-resistant Staphylococcus aureus (MRSA) has resulted in reduced susceptibility of MRSA to this drug. It is important to optimize vancomycin dosing in patients who are undergoing hemodialysis to attain a pre-hemodialysis serum concentration sufficient to eradicate MRSA, in accordance with recent guideline recommendations. Objectives: To establish the optimal strategy for vancomycin loading dose in patients undergoing hemodialysis and to explore the determinants of pre-hemodialysis serum concentration of vancomycin measured in these patients. Methods: A prospective observational cohort study was conducted between January and June 2010. Eligible participants were adults with established stage 5 chronic kidney disease who were undergoing inpatient hemodialysis. Data were collected on loading dose administered, body weight, serum concentration of vancomycin before the subsequent hemodialysis session (pre-hemodialysis concentration), and time between end of vancomycin infusion and measurement of pre-hemodialysis serum concentration. Multivariate stepwise linear regression was performed to examine independent associations between variables and measured pre-hemodialysis serum concentration of vancomycin. Results: Eighty-one patients were included in the study. Of 24 patients who achieved the recommended pre-hemodialysis serum concentration of vancomycin (15-20 mg/L), 14 had a loading dose between 15 and 20 mg/kg. Further analysis suggested that the pre-hemodialysis serum concentration of vancomycin was independently associated with weight-based loading dose (mg/kg) (β = 0.293, p = 0.003), age (β = -0.358, p < 0.001), and time between administration of the loading dose and initiation of hemodialysis (β = -0.247, p = 0.011). Conclusions: The findings of this study indicate that a loading dose of 15-20 mg/kg (actual body weight) is likely to yield an optimal pre-hemodialysis serum concentration at a median elapsed time of 24 h. In addition to loading dose, patient age and time between administration of the loading dose and initiation of hemodialysis also influenced the pre-hemodialysis serum concentration of the drug.