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  • Vancomycin population pharmacokinetics for adult patients with sepsis or septic shock: are current dosing regimens sufficient?

    Author(s)
    Heffernan, AJ
    Germano, A
    Sime, FB
    Roberts, Jason A
    Kimura, E
    Griffith University Author(s)
    Heffernan, Aaron J.
    Year published
    2019
    Metadata
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    Abstract
    Purpose: Vancomycin is commonly used for the management of severe infections; however, vancomycin dosing may be challenging in critically ill patients. This observational study aims to describe the population pharmacokinetics of vancomycin in adult patients with sepsis or septic shock. Methods: A single-centre retrospective review of adult patients with sepsis or septic shock receiving vancomycin with therapeutic drug monitoring was undertaken. Blood samples taken 1 h after the vancomycin infusion cessation and 30 min prior to the next dose were assayed using the Vitros Crea Slide method. Vancomycin concentrations determined ...
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    Purpose: Vancomycin is commonly used for the management of severe infections; however, vancomycin dosing may be challenging in critically ill patients. This observational study aims to describe the population pharmacokinetics of vancomycin in adult patients with sepsis or septic shock. Methods: A single-centre retrospective review of adult patients with sepsis or septic shock receiving vancomycin with therapeutic drug monitoring was undertaken. Blood samples taken 1 h after the vancomycin infusion cessation and 30 min prior to the next dose were assayed using the Vitros Crea Slide method. Vancomycin concentrations determined on different days were included. A pharmacokinetic model was developed using Pmetrics for R. Monte Carlo dosing simulations were performed using the final model. Results: Vancomycin concentrations were available for 27 adult patients admitted to the intensive care unit with sepsis or septic shock. A one-compartment pharmacokinetic model with inter-occasion variability of clearance and volume of distribution before and after 72 h adequately described the data. Creatinine clearance normalized to body surface area was included as a covariate on vancomycin clearance. The clearance and volume of distribution within 72 h of admission were 7.29 L/h and 54.20 L, respectively. Monte Carlo simulations suggested that for patients with a creatinine clearance of ≥ 80 mL/min/1.73 m2, vancomycin doses of ≥ 2 g every 8 h are required to consistently achieve key therapeutic targets. Conclusions: Vancomycin doses ≥ 2 g every 8 h in adult patients with sepsis or septic shock with a creatinine clearance ≥ 80 mL/min/1.73 m2 are likely needed to achieve an optimal therapeutic exposure.
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    Journal Title
    European Journal of Clinical Pharmacology
    Volume
    75
    Issue
    9
    DOI
    https://doi.org/10.1007/s00228-019-02694-1
    Subject
    Pharmacology and pharmaceutical sciences
    Pharmacokinetics
    Sepsis
    Septic shock
    Therapeutic drug monitoring
    Vancomycin
    Publication URI
    http://hdl.handle.net/10072/386833
    Collection
    • Journal articles

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