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 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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Acknowledgements
A.J.H. would like to acknowledge funding from a Griffith School of Medicine Research Higher degree scholarship. F.B.S. acknowledges funding from the University of Queensland Post-doctoral Fellowship. J.A.R. would like to recognize funding from the Australian National Health and Medical Research Council for a Centre of Research Excellence (APP1099452) and a Practitioner Fellowship (APP1117065).
Funding
E.K. and A.G. would like to acknowledge funding from the Science and Technology Secretariat of Paraná State, Brazil for this project.
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A.J.H.—conceptualisation, data analysis, writing—original draft.
A.G.—conceptualisation, data curation, project administration, writing—review and editing.
F.B.S.—data analysis, writing—review and editing.
J.A.R.—conceptualisation, data analysis, writing—review and editing.
E.K.—conceptualisation, data curation, funding acquisition, project administration, writing—review and editing.
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Heffernan, A.J., Germano, A., Sime, F.B. et al. Vancomycin population pharmacokinetics for adult patients with sepsis or septic shock: are current dosing regimens sufficient?. Eur J Clin Pharmacol 75, 1219–1226 (2019). https://doi.org/10.1007/s00228-019-02694-1
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DOI: https://doi.org/10.1007/s00228-019-02694-1