DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current β-Lactam Antibiotic Doses Sufficient for Critically III Patients?
Identifieur interne : 004223 ( Main/Exploration ); précédent : 004222; suivant : 004224DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current β-Lactam Antibiotic Doses Sufficient for Critically III Patients?
Auteurs : Jason A. Roberts [Australie] ; Sanjoy K. Paul [Australie] ; Murat Akova [Turquie] ; Matteo Bassetti [Italie] ; Jan J. De Waele [Belgique] ; George Dimopoulos [Grèce] ; Kirsi-Maija Kaukonen [Finlande] ; Despoina Koulenti [Australie, Grèce] ; Claude Martin [France] ; Philippe Montravers [France] ; Jordi Rello [Espagne] ; Andrew Rhodes [Royaume-Uni] ; Therese Starr [Australie] ; Steven C. Wallis [Australie] ; Jeffrey Lipman [Australie]Source :
- Clinical infectious diseases [ 1058-4838 ] ; 2014.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Antibiotique, Homme.
English descriptors
- KwdEn :
Abstract
Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome. Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% fT>MIC) and 100% (100% fT>MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome. Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f T >MIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P = .009). Positive clinical outcome was associated with increasing 50% fT>MIC and 100% f T>MIC ratios (OR, 1.02 and 1.56, respectively; P < .03), with significant interaction with sickness severity status. Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.
Affiliations:
- Australie, Belgique, Espagne, Finlande, France, Grèce, Italie, Royaume-Uni, Turquie
- Angleterre, Attique (région), Grand Londres, Provence-Alpes-Côte d'Azur
- Athènes, Londres, Marseille
- Université de Londres
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current β-Lactam Antibiotic Doses Sufficient for Critically III Patients?</title><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"><inist:fA14 i1="01"><s1>Burns Trauma and Critical Care Research Centre, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Royal Brisbane and Women's Hospital, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Paul, Sanjoy K" sort="Paul, Sanjoy K" uniqKey="Paul S" first="Sanjoy K." last="Paul">Sanjoy K. Paul</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>2 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Queensland Clinical Trials and Biostatistics Centre, School of Population Health, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>2 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Akova, Murat" sort="Akova, Murat" uniqKey="Akova M" first="Murat" last="Akova">Murat Akova</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>School of Medicine, Hacettepe University</s1><s2>Ankara</s2><s3>TUR</s3><sZ>3 aut.</sZ></inist:fA14><country>Turquie</country><wicri:noRegion>Ankara</wicri:noRegion></affiliation></author><author><name sortKey="Bassetti, Matteo" sort="Bassetti, Matteo" uniqKey="Bassetti M" first="Matteo" last="Bassetti">Matteo Bassetti</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Azienda Ospedaliera Universitaria Santa Maria della Misericordia</s1><s2>Udine</s2><s3>ITA</s3><sZ>4 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Azienda Ospedaliera Universitaria Santa Maria della Misericordia</wicri:noRegion></affiliation></author><author><name sortKey="De Waele, Jan J" sort="De Waele, Jan J" uniqKey="De Waele J" first="Jan J." last="De Waele">Jan J. De Waele</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Ghent University Hospital</s1><s2>Ghent</s2><s3>BEL</s3><sZ>5 aut.</sZ></inist:fA14><country>Belgique</country><wicri:noRegion>Ghent University Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Dimopoulos, George" sort="Dimopoulos, George" uniqKey="Dimopoulos G" first="George" last="Dimopoulos">George Dimopoulos</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Attikon University Hospital</s1><s2>Athens</s2><s3>GRC</s3><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Grèce</country><placeName><settlement type="city">Athènes</settlement><region nuts="2" type="region">Attique (région)</region></placeName></affiliation></author><author><name sortKey="Kaukonen, Kirsi Maija" sort="Kaukonen, Kirsi Maija" uniqKey="Kaukonen K" first="Kirsi-Maija" last="Kaukonen">Kirsi-Maija Kaukonen</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Helsinki University Central Hospital</s1><s2>Helsinki</s2><s3>FIN</s3><sZ>7 aut.</sZ></inist:fA14><country>Finlande</country><wicri:noRegion>Helsinki University Central Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Koulenti, Despoina" sort="Koulenti, Despoina" uniqKey="Koulenti D" first="Despoina" last="Koulenti">Despoina Koulenti</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Burns Trauma and Critical Care Research Centre, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Attikon University Hospital</s1><s2>Athens</s2><s3>GRC</s3><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Grèce</country><placeName><settlement type="city">Athènes</settlement><region nuts="2" type="region">Attique (région)</region></placeName></affiliation></author><author><name sortKey="Martin, Claude" sort="Martin, Claude" uniqKey="Martin C" first="Claude" last="Martin">Claude Martin</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>Hospital Nord</s1><s2>Marseille</s2><s3>FRA</s3><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>AzuRea Group</s1><s3>FRA</s3><sZ>9 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>AzuRea Group</wicri:noRegion><wicri:noRegion>AzuRea Group</wicri:noRegion></affiliation></author><author><name sortKey="Montravers, Philippe" sort="Montravers, Philippe" uniqKey="Montravers P" first="Philippe" last="Montravers">Philippe Montravers</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Université Paris VII</s1><s3>FRA</s3><sZ>10 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Université Paris VII</wicri:noRegion><wicri:noRegion>Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Université Paris VII</wicri:noRegion></affiliation></author><author><name sortKey="Rello, Jordi" sort="Rello, Jordi" uniqKey="Rello J" first="Jordi" last="Rello">Jordi Rello</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>CIBERES, Vall d'Hebron Institut of Research, Universitat Autonoma de Barcelona</s1><s3>ESP</s3><sZ>11 aut.</sZ></inist:fA14><country>Espagne</country><wicri:noRegion>CIBERES, Vall d'Hebron Institut of Research, Universitat Autonoma de Barcelona</wicri:noRegion></affiliation></author><author><name sortKey="Rhodes, Andrew" sort="Rhodes, Andrew" uniqKey="Rhodes A" first="Andrew" last="Rhodes">Andrew Rhodes</name><affiliation wicri:level="4"><inist:fA14 i1="14"><s1>St George's Healthcare NHS Trust and St George's University of London</s1><s3>GBR</s3><sZ>12 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">Université de Londres</orgName></affiliation></author><author><name sortKey="Starr, Therese" sort="Starr, Therese" uniqKey="Starr T" first="Therese" last="Starr">Therese Starr</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Royal Brisbane and Women's Hospital, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Wallis, Steven C" sort="Wallis, Steven C" uniqKey="Wallis S" first="Steven C." last="Wallis">Steven C. Wallis</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Burns Trauma and Critical Care Research Centre, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Lipman, Jeffrey" sort="Lipman, Jeffrey" uniqKey="Lipman J" first="Jeffrey" last="Lipman">Jeffrey Lipman</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Burns Trauma and Critical Care Research Centre, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Royal Brisbane and Women's Hospital, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">14-0124071</idno><date when="2014">2014</date><idno type="stanalyst">PASCAL 14-0124071 INIST</idno><idno type="RBID">Pascal:14-0124071</idno><idno type="wicri:Area/PascalFrancis/Corpus">000453</idno><idno type="wicri:Area/PascalFrancis/Curation">005A09</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000369</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000369</idno><idno type="wicri:doubleKey">1058-4838:2014:Roberts J:dali:defining:antibiotic</idno><idno type="wicri:Area/Main/Merge">004293</idno><idno type="wicri:Area/Main/Curation">004223</idno><idno type="wicri:Area/Main/Exploration">004223</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current β-Lactam Antibiotic Doses Sufficient for Critically III Patients?</title><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"><inist:fA14 i1="01"><s1>Burns Trauma and Critical Care Research Centre, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Royal Brisbane and Women's Hospital, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Paul, Sanjoy K" sort="Paul, Sanjoy K" uniqKey="Paul S" first="Sanjoy K." last="Paul">Sanjoy K. Paul</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>2 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Queensland Clinical Trials and Biostatistics Centre, School of Population Health, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>2 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Akova, Murat" sort="Akova, Murat" uniqKey="Akova M" first="Murat" last="Akova">Murat Akova</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>School of Medicine, Hacettepe University</s1><s2>Ankara</s2><s3>TUR</s3><sZ>3 aut.</sZ></inist:fA14><country>Turquie</country><wicri:noRegion>Ankara</wicri:noRegion></affiliation></author><author><name sortKey="Bassetti, Matteo" sort="Bassetti, Matteo" uniqKey="Bassetti M" first="Matteo" last="Bassetti">Matteo Bassetti</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Azienda Ospedaliera Universitaria Santa Maria della Misericordia</s1><s2>Udine</s2><s3>ITA</s3><sZ>4 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Azienda Ospedaliera Universitaria Santa Maria della Misericordia</wicri:noRegion></affiliation></author><author><name sortKey="De Waele, Jan J" sort="De Waele, Jan J" uniqKey="De Waele J" first="Jan J." last="De Waele">Jan J. De Waele</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Ghent University Hospital</s1><s2>Ghent</s2><s3>BEL</s3><sZ>5 aut.</sZ></inist:fA14><country>Belgique</country><wicri:noRegion>Ghent University Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Dimopoulos, George" sort="Dimopoulos, George" uniqKey="Dimopoulos G" first="George" last="Dimopoulos">George Dimopoulos</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Attikon University Hospital</s1><s2>Athens</s2><s3>GRC</s3><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Grèce</country><placeName><settlement type="city">Athènes</settlement><region nuts="2" type="region">Attique (région)</region></placeName></affiliation></author><author><name sortKey="Kaukonen, Kirsi Maija" sort="Kaukonen, Kirsi Maija" uniqKey="Kaukonen K" first="Kirsi-Maija" last="Kaukonen">Kirsi-Maija Kaukonen</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Helsinki University Central Hospital</s1><s2>Helsinki</s2><s3>FIN</s3><sZ>7 aut.</sZ></inist:fA14><country>Finlande</country><wicri:noRegion>Helsinki University Central Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Koulenti, Despoina" sort="Koulenti, Despoina" uniqKey="Koulenti D" first="Despoina" last="Koulenti">Despoina Koulenti</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Burns Trauma and Critical Care Research Centre, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Attikon University Hospital</s1><s2>Athens</s2><s3>GRC</s3><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Grèce</country><placeName><settlement type="city">Athènes</settlement><region nuts="2" type="region">Attique (région)</region></placeName></affiliation></author><author><name sortKey="Martin, Claude" sort="Martin, Claude" uniqKey="Martin C" first="Claude" last="Martin">Claude Martin</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>Hospital Nord</s1><s2>Marseille</s2><s3>FRA</s3><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>AzuRea Group</s1><s3>FRA</s3><sZ>9 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>AzuRea Group</wicri:noRegion><wicri:noRegion>AzuRea Group</wicri:noRegion></affiliation></author><author><name sortKey="Montravers, Philippe" sort="Montravers, Philippe" uniqKey="Montravers P" first="Philippe" last="Montravers">Philippe Montravers</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Université Paris VII</s1><s3>FRA</s3><sZ>10 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Université Paris VII</wicri:noRegion><wicri:noRegion>Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Université Paris VII</wicri:noRegion></affiliation></author><author><name sortKey="Rello, Jordi" sort="Rello, Jordi" uniqKey="Rello J" first="Jordi" last="Rello">Jordi Rello</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>CIBERES, Vall d'Hebron Institut of Research, Universitat Autonoma de Barcelona</s1><s3>ESP</s3><sZ>11 aut.</sZ></inist:fA14><country>Espagne</country><wicri:noRegion>CIBERES, Vall d'Hebron Institut of Research, Universitat Autonoma de Barcelona</wicri:noRegion></affiliation></author><author><name sortKey="Rhodes, Andrew" sort="Rhodes, Andrew" uniqKey="Rhodes A" first="Andrew" last="Rhodes">Andrew Rhodes</name><affiliation wicri:level="4"><inist:fA14 i1="14"><s1>St George's Healthcare NHS Trust and St George's University of London</s1><s3>GBR</s3><sZ>12 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">Université de Londres</orgName></affiliation></author><author><name sortKey="Starr, Therese" sort="Starr, Therese" uniqKey="Starr T" first="Therese" last="Starr">Therese Starr</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Royal Brisbane and Women's Hospital, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Wallis, Steven C" sort="Wallis, Steven C" uniqKey="Wallis S" first="Steven C." last="Wallis">Steven C. Wallis</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Burns Trauma and Critical Care Research Centre, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Lipman, Jeffrey" sort="Lipman, Jeffrey" uniqKey="Lipman J" first="Jeffrey" last="Lipman">Jeffrey Lipman</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Burns Trauma and Critical Care Research Centre, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Royal Brisbane and Women's Hospital, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Clinical infectious diseases</title><title level="j" type="abbreviated">Clin. infect. dis.</title><idno type="ISSN">1058-4838</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Clinical infectious diseases</title><title level="j" type="abbreviated">Clin. infect. dis.</title><idno type="ISSN">1058-4838</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibacterial agent</term><term>Antibiotic</term><term>Dose</term><term>Human</term><term>Infection</term><term>Intensive care unit</term><term>β-Lactams</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Antibactérien</term><term>β-Lactamines</term><term>Antibiotique</term><term>Unité soin intensif</term><term>Dose</term><term>Homme</term><term>Infection</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Antibiotique</term><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome. Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% fT<sub>>MIC</sub>) and 100% (100% fT<sub>>MIC</sub>) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome. Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f T <sub>>MIC</sub> and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P = .009). Positive clinical outcome was associated with increasing 50% fT<sub>>MIC</sub> and 100% f T<sub>>MIC</sub> ratios (OR, 1.02 and 1.56, respectively; P < .03), with significant interaction with sickness severity status. Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Belgique</li><li>Espagne</li><li>Finlande</li><li>France</li><li>Grèce</li><li>Italie</li><li>Royaume-Uni</li><li>Turquie</li></country><region><li>Angleterre</li><li>Attique (région)</li><li>Grand Londres</li><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Athènes</li><li>Londres</li><li>Marseille</li></settlement><orgName><li>Université de Londres</li></orgName></list><tree><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><name sortKey="Koulenti, Despoina" sort="Koulenti, Despoina" uniqKey="Koulenti D" first="Despoina" last="Koulenti">Despoina Koulenti</name><name sortKey="Lipman, Jeffrey" sort="Lipman, Jeffrey" uniqKey="Lipman J" first="Jeffrey" last="Lipman">Jeffrey Lipman</name><name sortKey="Lipman, Jeffrey" sort="Lipman, Jeffrey" uniqKey="Lipman J" first="Jeffrey" last="Lipman">Jeffrey Lipman</name><name sortKey="Paul, Sanjoy K" sort="Paul, Sanjoy K" uniqKey="Paul S" first="Sanjoy K." last="Paul">Sanjoy K. Paul</name><name sortKey="Paul, Sanjoy K" sort="Paul, Sanjoy K" uniqKey="Paul S" first="Sanjoy K." last="Paul">Sanjoy K. Paul</name><name sortKey="Roberts, Jason A" sort="Roberts, Jason A" uniqKey="Roberts J" first="Jason A." last="Roberts">Jason A. Roberts</name><name sortKey="Starr, Therese" sort="Starr, Therese" uniqKey="Starr T" first="Therese" last="Starr">Therese Starr</name><name sortKey="Wallis, Steven C" sort="Wallis, Steven C" uniqKey="Wallis S" first="Steven C." last="Wallis">Steven C. Wallis</name></country><country name="Turquie"><noRegion><name sortKey="Akova, Murat" sort="Akova, Murat" uniqKey="Akova M" first="Murat" last="Akova">Murat Akova</name></noRegion></country><country name="Italie"><noRegion><name sortKey="Bassetti, Matteo" sort="Bassetti, Matteo" uniqKey="Bassetti M" first="Matteo" last="Bassetti">Matteo Bassetti</name></noRegion></country><country name="Belgique"><noRegion><name sortKey="De Waele, Jan J" sort="De Waele, Jan J" uniqKey="De Waele J" first="Jan J." last="De Waele">Jan J. De Waele</name></noRegion></country><country name="Grèce"><region name="Attique (région)"><name sortKey="Dimopoulos, George" sort="Dimopoulos, George" uniqKey="Dimopoulos G" first="George" last="Dimopoulos">George Dimopoulos</name></region><name sortKey="Koulenti, Despoina" sort="Koulenti, Despoina" uniqKey="Koulenti D" first="Despoina" last="Koulenti">Despoina Koulenti</name></country><country name="Finlande"><noRegion><name sortKey="Kaukonen, Kirsi Maija" sort="Kaukonen, Kirsi Maija" uniqKey="Kaukonen K" first="Kirsi-Maija" last="Kaukonen">Kirsi-Maija Kaukonen</name></noRegion></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Martin, Claude" sort="Martin, Claude" uniqKey="Martin C" first="Claude" last="Martin">Claude Martin</name></region><name sortKey="Martin, Claude" sort="Martin, Claude" uniqKey="Martin C" first="Claude" last="Martin">Claude Martin</name><name sortKey="Montravers, Philippe" sort="Montravers, Philippe" uniqKey="Montravers P" first="Philippe" last="Montravers">Philippe Montravers</name></country><country name="Espagne"><noRegion><name sortKey="Rello, Jordi" sort="Rello, Jordi" uniqKey="Rello J" first="Jordi" last="Rello">Jordi Rello</name></noRegion></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Rhodes, Andrew" sort="Rhodes, Andrew" uniqKey="Rhodes A" first="Andrew" last="Rhodes">Andrew Rhodes</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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