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

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 si...

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Published in:European Journal of Clinical Pharmacology Vol. 75; no. 9; pp. 1219 - 1227
Main Authors: Heffernan, A. J., Germano, A., Sime, F. B., Roberts, Jason A., Kimura, E.
Format: equations & formulas research tables/charts Journal Article
Published: Springer Nature Sep2019
Online Access:View this record in EBSCOhost
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      issn: 00316970
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      dt: Sep2019
      vid: 75
      iid: 9
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      pub: Springer Nature
      place: New York, New York
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        138111093
        10.1007/s00228-019-02694-1
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        atl: Vancomycin population pharmacokinetics for adult patients with sepsis or septic shock: are current dosing regimens sufficient?
      aug:
        au:
          Heffernan, A. J.
          Germano, A.
          Sime, F. B.
          Roberts, Jason A.
          Kimura, E.
        affil: Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia
      sug:
        subj:
          Vancomycin Pharmacokinetics
          Sepsis Drug Therapy
          Human
          Shock, Septic Drug Therapy
          Nonexperimental Studies
          Retrospective Design
          Drug Monitoring
          Blood Specimen Collection
          Vancomycin Administration and Dosage
          Intensive Care Units
          Creatinine
          Body Surface Area
          Computer Simulation
          Adult
          Systems Analysis
          Critically Ill Patients
          Dosage Calculation
          Models, Statistical
          Adult: 19-44 years
      ab: 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.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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