Intensive Care Medicine

, Volume 43, Issue 7, pp 1021–1032 | Cite as

The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections

  • T. Tängdén
  • V. Ramos Martín
  • T. W. Felton
  • E. I. Nielsen
  • S. Marchand
  • R. J. Brüggemann
  • J. B. Bulitta
  • M. Bassetti
  • U. Theuretzbacher
  • B. T. Tsuji
  • D. W. Wareham
  • L. E. Friberg
  • J. J. De Waele
  • V. H. Tam
  • Jason A. RobertsEmail author
  • on behalf of the Infection Section for the European Society of Intensive Care Medicine, the Pharmacokinetics and Pharmacodynamics Study Group of the European Society of Clinical Microbiology and Infectious Diseases, the International Society of Anti-Infective Pharmacology and the Critically Ill Patients Study Group of European Society of Clinical Microbiology and Infectious Diseases


Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed. Use of such regimens often results in inadequate antimicrobial concentrations at the site of infection and is associated with poor patient outcomes. In this article, we describe the potential of in vitro and in vivo infection models, clinical pharmacokinetic data and pharmacokinetic/pharmacodynamic models to guide the design of more effective antimicrobial dosing regimens. Individualised dosing, based on population PK models and patient factors (e.g. renal function and weight) known to influence antimicrobial PK, increases the probability of achieving therapeutic drug exposures while at the same time avoiding toxic concentrations. When therapeutic drug monitoring (TDM) is applied, early dose adaptation to the needs of the individual patient is possible. TDM is likely to be of particular importance for infected critically ill patients, where profound PK changes are present and prompt appropriate antibiotic therapy is crucial. In the light of the continued high mortality rates in critically ill patients with severe infections, a paradigm shift to refined dosing strategies for antimicrobials is warranted to enhance the probability of achieving drug concentrations that increase the likelihood of clinical success.


Individualised dosing Antibiotics Pharmacokinetics Pharmacodynamics Mathematical modelling 



Jason A. Roberts is funded by a Practitioner Fellowship from the National Health and Medical Research Council of Australia (APP1117065) and would like to acknowledge funding from the Australian National Health and Medical Research Council for Centre of Research Excellence (APP1099452).

Compliance with ethical standards

Conflicts of interest

JA Roberts has received grants from MSD and Cardeas Pharma; JAR has consulted for Astellas, bioMerieux, MSD and Infectopharm.


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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2017

Authors and Affiliations

  • T. Tängdén
    • 1
  • V. Ramos Martín
    • 2
  • T. W. Felton
    • 3
  • E. I. Nielsen
    • 4
  • S. Marchand
    • 5
    • 6
  • R. J. Brüggemann
    • 7
  • J. B. Bulitta
    • 8
  • M. Bassetti
    • 9
  • U. Theuretzbacher
    • 10
  • B. T. Tsuji
    • 11
  • D. W. Wareham
    • 12
  • L. E. Friberg
    • 4
  • J. J. De Waele
    • 13
  • V. H. Tam
    • 14
  • Jason A. Roberts
    • 15
    • 16
    Email author
  • on behalf of the Infection Section for the European Society of Intensive Care Medicine, the Pharmacokinetics and Pharmacodynamics Study Group of the European Society of Clinical Microbiology and Infectious Diseases, the International Society of Anti-Infective Pharmacology and the Critically Ill Patients Study Group of European Society of Clinical Microbiology and Infectious Diseases
  1. 1.Department of Medical Sciences, Section of Infectious DiseasesUppsala UniversityUppsalaSweden
  2. 2.Department of Molecular and Clinical PharmacologyUniversity of LiverpoolLiverpoolUK
  3. 3.Intensive Care UnitUniversity Hospital of South ManchesterManchesterUK
  4. 4.Department of Pharmaceutical BiosciencesUppsala UniversityUppsalaSweden
  5. 5.Inserm U1070Pole Biologie SantéPoitiersFrance
  6. 6.UFR Médecine-PharmacieUniversité de PoitiersPoitiersFrance
  7. 7.Department of PharmacyRadboud University Medical CenterNijmegenThe Netherlands
  8. 8.Center for Pharmacometrics and Systems Pharmacology, College of PharmacyUniversity of FloridaOrlandoUSA
  9. 9.Infectious Diseases DivisionSanta Maria della Misericordia University Hospital and University of UdineUdineItaly
  10. 10.Center for Anti-Infective AgentsViennaAustria
  11. 11.School of Pharmacy and Pharmaceutical SciencesUniversity at Buffalo, State University of New YorkBuffaloUSA
  12. 12.Antimicrobial Research Group, Barts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUK
  13. 13.Department of Critical Care MedicineGhent University HospitalGhentBelgium
  14. 14.Department of Pharmacy Practice and Translational ResearchUniversity of Houston College of PharmacyHoustonUSA
  15. 15.Burns, Trauma and Critical Care Research Centre and Centre for Translational Anti-infective PharmacodynamicsThe University of QueenslandBrisbaneAustralia
  16. 16.Departments of Intensive Care Medicine and PharmacyRoyal Brisbane and Women’s HospitalBrisbaneAustralia

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