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

Tangden, T., Ramos Martin, V., Felton, T. W., Nielsen, E. I., Marchand, S., Bruggemann, R. J., Bulitta, J. B., Bassetti, M., Theuretzbacher, U., Tsuji, B. T., Wareham, D. W., Friberg, L. E., de Waele, J. J., Tam, V. H. and Roberts, J. A. (2017) The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections. Intensive Care Medicine, 43 7: 1021-1032. doi:10.1007/s00134-017-4780-6

Author Tangden, T.
Ramos Martin, V.
Felton, T. W.
Nielsen, E. I.
Marchand, S.
Bruggemann, R. J.
Bulitta, J. B.
Bassetti, M.
Theuretzbacher, U.
Tsuji, B. T.
Wareham, D. W.
Friberg, L. E.
de Waele, J. J.
Tam, V. H.
Roberts, J. A.
Title The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections
Journal name Intensive Care Medicine   Check publisher's open access policy
ISSN 1432-1238
Publication date 2017-04-13
Year available 2017
Sub-type Article (original research)
DOI 10.1007/s00134-017-4780-6
Open Access Status Not yet assessed
Volume 43
Issue 7
Start page 1021
End page 1032
Total pages 12
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Subject 2706 Critical Care and Intensive Care Medicine
Abstract 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.
Keyword Antibiotics
Individualised dosing
Mathematical modelling
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1117065
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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