The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections.
Identifieur interne : 000176 ( Main/Exploration ); précédent : 000175; suivant : 000177The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections.
Auteurs : T. T Ngdén [Suède] ; V. Ramos Martín [Royaume-Uni] ; T W Felton [Royaume-Uni] ; E I Nielsen [Suède] ; S. Marchand [France] ; R J Brüggemann [Pays-Bas] ; J B Bulitta [États-Unis] ; M. Bassetti [Italie] ; U. Theuretzbacher [Autriche] ; B T Tsuji [États-Unis] ; D W Wareham [Royaume-Uni] ; L E Friberg [Suède] ; J J De Waele [Belgique] ; V H Tam [États-Unis] ; Jason A. Roberts [Australie]Source :
- Intensive care medicine [ 1432-1238 ] ; 2017.
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.
DOI: 10.1007/s00134-017-4780-6
PubMed: 28409203
Affiliations:
- Australie, Autriche, Belgique, France, Italie, Pays-Bas, Royaume-Uni, Suède, États-Unis
- Angleterre, East Middle Sweden, Grand Londres, Grand Manchester, Gueldre, Nouvelle-Aquitaine, Poitou-Charentes, Svealand, Texas, Vienne (Autriche), État de New York
- Buffalo (New York), Houston, Londres, Manchester, Nimègue, Poitiers, Uppsala, Vienne (Autriche)
- Université d'Uppsala, Université d'État de New York à Buffalo, Université de Londres
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T Ngdén</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="Ramos Martin, V" sort="Ramos Martin, V" uniqKey="Ramos Martin V" first="V" last="Ramos Martín">V. Ramos Martín</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool</wicri:regionArea><wicri:noRegion>Liverpool</wicri:noRegion></affiliation></author><author><name sortKey="Felton, T W" sort="Felton, T W" uniqKey="Felton T" first="T W" last="Felton">T W Felton</name><affiliation wicri:level="3"><nlm:affiliation>Intensive Care Unit, University Hospital of South Manchester, Manchester, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Intensive Care Unit, University Hospital of South Manchester, Manchester</wicri:regionArea><placeName><settlement type="city">Manchester</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Nielsen, E I" sort="Nielsen, E I" uniqKey="Nielsen E" first="E I" last="Nielsen">E I Nielsen</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Pharmaceutical Biosciences, Uppsala University, Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="Marchand, S" sort="Marchand, S" uniqKey="Marchand S" first="S" last="Marchand">S. Marchand</name><affiliation wicri:level="3"><nlm:affiliation>Inserm U1070, Pole Biologie Santé, Poitiers, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm U1070, Pole Biologie Santé, Poitiers</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Poitou-Charentes</region><settlement type="city">Poitiers</settlement></placeName></affiliation></author><author><name sortKey="Bruggemann, R J" sort="Bruggemann, R J" uniqKey="Bruggemann R" first="R J" last="Brüggemann">R J Brüggemann</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pharmacy, Radboud University Medical Center, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Bulitta, J B" sort="Bulitta, J B" uniqKey="Bulitta J" first="J B" last="Bulitta">J B Bulitta</name><affiliation wicri:level="1"><nlm:affiliation>Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando</wicri:regionArea><wicri:noRegion>Orlando</wicri:noRegion></affiliation></author><author><name sortKey="Bassetti, M" sort="Bassetti, M" uniqKey="Bassetti M" first="M" last="Bassetti">M. Bassetti</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Division, Santa Maria della Misericordia University Hospital and University of Udine, Udine, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Infectious Diseases Division, Santa Maria della Misericordia University Hospital and University of Udine, Udine</wicri:regionArea><wicri:noRegion>Udine</wicri:noRegion></affiliation></author><author><name sortKey="Theuretzbacher, U" sort="Theuretzbacher, U" uniqKey="Theuretzbacher U" first="U" last="Theuretzbacher">U. Theuretzbacher</name><affiliation wicri:level="3"><nlm:affiliation>Center for Anti-Infective Agents, Vienna, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Center for Anti-Infective Agents, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Tsuji, B T" sort="Tsuji, B T" uniqKey="Tsuji B" first="B T" last="Tsuji">B T Tsuji</name><affiliation wicri:level="4"><nlm:affiliation>School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo</wicri:regionArea><orgName type="university">Université d'État de New York à Buffalo</orgName><placeName><settlement type="city">Buffalo (New York)</settlement><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Wareham, D W" sort="Wareham, D W" uniqKey="Wareham D" first="D W" last="Wareham">D W Wareham</name><affiliation wicri:level="4"><nlm:affiliation>Antimicrobial Research Group, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Antimicrobial Research Group, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region><settlement type="city">Londres</settlement></placeName><orgName type="university">Université de Londres</orgName></affiliation></author><author><name sortKey="Friberg, L E" sort="Friberg, L E" uniqKey="Friberg L" first="L E" last="Friberg">L E Friberg</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Pharmaceutical Biosciences, Uppsala University, Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="De Waele, J J" sort="De Waele, J J" uniqKey="De Waele J" first="J J" last="De Waele">J J De Waele</name><affiliation wicri:level="1"><nlm:affiliation>Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Department of Critical Care Medicine, Ghent University Hospital, Ghent</wicri:regionArea><wicri:noRegion>Ghent</wicri:noRegion></affiliation></author><author><name sortKey="Tam, V H" sort="Tam, V H" uniqKey="Tam V" first="V H" last="Tam">V H Tam</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston</wicri:regionArea><placeName><settlement type="city">Houston</settlement><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Roberts, Jason A" sort="Roberts, Jason A" uniqKey="Roberts J" first="Jason A" last="Roberts">Jason A. Roberts</name><affiliation wicri:level="1"><nlm:affiliation>Burns, Trauma and Critical Care Research Centre and Centre for Translational Anti-infective Pharmacodynamics, The University of Queensland, Brisbane, Australia. j.roberts2@uq.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Burns, Trauma and Critical Care Research Centre and Centre for Translational Anti-infective Pharmacodynamics, The University of Queensland, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author></analytic><series><title level="j">Intensive care medicine</title><idno type="eISSN">1432-1238</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Autriche</li><li>Belgique</li><li>France</li><li>Italie</li><li>Pays-Bas</li><li>Royaume-Uni</li><li>Suède</li><li>États-Unis</li></country><region><li>Angleterre</li><li>East Middle Sweden</li><li>Grand Londres</li><li>Grand Manchester</li><li>Gueldre</li><li>Nouvelle-Aquitaine</li><li>Poitou-Charentes</li><li>Svealand</li><li>Texas</li><li>Vienne (Autriche)</li><li>État de New York</li></region><settlement><li>Buffalo (New York)</li><li>Houston</li><li>Londres</li><li>Manchester</li><li>Nimègue</li><li>Poitiers</li><li>Uppsala</li><li>Vienne (Autriche)</li></settlement><orgName><li>Université d'Uppsala</li><li>Université d'État de New York à Buffalo</li><li>Université de Londres</li></orgName></list><tree><country name="Suède"><region name="Svealand"><name sortKey="T Ngden, T" sort="T Ngden, T" uniqKey="T Ngden T" first="T" last="T Ngdén">T. T Ngdén</name></region><name sortKey="Friberg, L E" sort="Friberg, L E" uniqKey="Friberg L" first="L E" last="Friberg">L E Friberg</name><name sortKey="Nielsen, E I" sort="Nielsen, E I" uniqKey="Nielsen E" first="E I" last="Nielsen">E I Nielsen</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Ramos Martin, V" sort="Ramos Martin, V" uniqKey="Ramos Martin V" first="V" last="Ramos Martín">V. Ramos Martín</name></noRegion><name sortKey="Felton, T W" sort="Felton, T W" uniqKey="Felton T" first="T W" last="Felton">T W Felton</name><name sortKey="Wareham, D W" sort="Wareham, D W" uniqKey="Wareham D" first="D W" last="Wareham">D W Wareham</name></country><country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Marchand, S" sort="Marchand, S" uniqKey="Marchand S" first="S" last="Marchand">S. Marchand</name></region></country><country name="Pays-Bas"><region name="Gueldre"><name sortKey="Bruggemann, R J" sort="Bruggemann, R J" uniqKey="Bruggemann R" first="R J" last="Brüggemann">R J Brüggemann</name></region></country><country name="États-Unis"><noRegion><name sortKey="Bulitta, J B" sort="Bulitta, J B" uniqKey="Bulitta J" first="J B" last="Bulitta">J B Bulitta</name></noRegion><name sortKey="Tam, V H" sort="Tam, V H" uniqKey="Tam V" first="V H" last="Tam">V H Tam</name><name sortKey="Tsuji, B T" sort="Tsuji, B T" uniqKey="Tsuji B" first="B T" last="Tsuji">B T Tsuji</name></country><country name="Italie"><noRegion><name sortKey="Bassetti, M" sort="Bassetti, M" uniqKey="Bassetti M" first="M" last="Bassetti">M. Bassetti</name></noRegion></country><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Theuretzbacher, U" sort="Theuretzbacher, U" uniqKey="Theuretzbacher U" first="U" last="Theuretzbacher">U. Theuretzbacher</name></region></country><country name="Belgique"><noRegion><name sortKey="De Waele, J J" sort="De Waele, J J" uniqKey="De Waele J" first="J J" last="De Waele">J J De Waele</name></noRegion></country><country name="Australie"><noRegion><name sortKey="Roberts, Jason A" sort="Roberts, Jason A" uniqKey="Roberts J" first="Jason A" last="Roberts">Jason A. Roberts</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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