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European Journal of Clinical Pharmacology

, Volume 75, Issue 9, pp 1219–1226 | Cite as

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

  • A. J. Heffernan
  • A. Germano
  • F. B. Sime
  • Jason A. RobertsEmail author
  • E. Kimura
Pharmacokinetics and Disposition

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.

Keywords

Vancomycin Pharmacokinetics Therapeutic drug monitoring Sepsis Septic shock 

Notes

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).

Authors’ individual contributions

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.

Funding information

E.K. and A.G. would like to acknowledge funding from the Science and Technology Secretariat of Paraná State, Brazil for this project.

Compliance with ethical standards

Conflict of interest

No authors report any relevant conflicts of interest to declare.

Ethics

Waiver of informed consent was granted by the local ethics committee (CAAE 62009816.9.0000.0104).

Supplementary material

228_2019_2694_MOESM1_ESM.docx (27 kb)
ESM 1 (DOCX 26 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Centre for Translational Anti-Infective Pharmacodynamics, School of PharmacyThe University of QueenslandBrisbaneAustralia
  2. 2.School of MedicineGriffith UniversityGold CoastAustralia
  3. 3.Department of Intensive Care MedicineUniversidade Estadual de Maringá HospitalMaringáBrazil
  4. 4.University of Queensland Centre for Clinical Research, Faculty of MedicineThe University of QueenslandHerstonAustralia
  5. 5.Pharmacy Department and Department of Intensive Care MedicineRoyal Brisbane and Women’s HospitalBrisbaneAustralia

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