Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: lessons from the DALI Study.
Identifieur interne : 001863 ( Ncbi/Merge ); précédent : 001862; suivant : 001864Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: lessons from the DALI Study.
Auteurs : J A Roberts [Australie] ; V. Stove [Belgique] ; J J De Waele [Belgique] ; B. Sipinkoski [Australie] ; B. Mcwhinney [Australie] ; J P J. Ungerer [Australie] ; M. Akova [Turquie] ; M. Bassetti [Italie] ; G. Dimopoulos [Grèce] ; K-M Kaukonen [Australie] ; D. Koulenti [Grèce] ; C. Martin [France] ; P. Montravers [France] ; J. Rello [Espagne] ; A. Rhodes [Royaume-Uni] ; T. Starr [Australie] ; S C Wallis [Australie] ; J. Lipman [Australie]Source :
- International journal of antimicrobial agents [ 1872-7913 ] ; 2014.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Antibactériens (administration et posologie), Antibactériens (métabolisme), Antibactériens (pharmacocinétique), Chromatographie, Coopération internationale, Femelle, Humains, Jeune adulte, Liaison aux protéines, Maladie grave, Mâle, Plasma sanguin (), Sujet âgé, Surveillance pharmacologique, Téicoplanine (administration et posologie), Téicoplanine (métabolisme), Téicoplanine (pharmacocinétique).
- MESH :
- administration et posologie : Antibactériens, Téicoplanine.
- métabolisme : Antibactériens, Téicoplanine.
- pharmacocinétique : Antibactériens, Téicoplanine.
- Adulte, Adulte d'âge moyen, Chromatographie, Coopération internationale, Femelle, Humains, Jeune adulte, Liaison aux protéines, Maladie grave, Mâle, Plasma sanguin, Sujet âgé, Surveillance pharmacologique.
English descriptors
- KwdEn :
- Adult, Aged, Anti-Bacterial Agents (administration & dosage), Anti-Bacterial Agents (metabolism), Anti-Bacterial Agents (pharmacokinetics), Chromatography, Critical Illness, Drug Monitoring, Female, Humans, International Cooperation, Male, Middle Aged, Plasma (chemistry), Protein Binding, Teicoplanin (administration & dosage), Teicoplanin (metabolism), Teicoplanin (pharmacokinetics), Young Adult.
- MESH :
- chemical , administration & dosage : Anti-Bacterial Agents, Teicoplanin.
- chemical , metabolism : Anti-Bacterial Agents, Teicoplanin.
- chemical , pharmacokinetics : Anti-Bacterial Agents, Teicoplanin.
- chemistry : Plasma.
- Adult, Aged, Chromatography, Critical Illness, Drug Monitoring, Female, Humans, International Cooperation, Male, Middle Aged, Protein Binding, Young Adult.
Abstract
The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2-26.0) and free 1.5 (0.7-2.5); trough, total 11.9 (10.2-22.7) and free 1.8 (0.6-2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5-15.6%) and 8.2% (5.5-16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (ρ = 0.79, P = 0.0021) and trough (ρ = 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.
DOI: 10.1016/j.ijantimicag.2014.01.023
PubMed: 24630304
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Bassetti</name><affiliation wicri:level="1"><nlm:affiliation>Azienda Ospedaliera-Universitaria 'Santa Maria della Misericordia', Udine, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Azienda Ospedaliera-Universitaria 'Santa Maria della Misericordia', Udine</wicri:regionArea><wicri:noRegion>Udine</wicri:noRegion></affiliation></author><author><name sortKey="Dimopoulos, G" sort="Dimopoulos, G" uniqKey="Dimopoulos G" first="G" last="Dimopoulos">G. Dimopoulos</name><affiliation wicri:level="3"><nlm:affiliation>'Attikon' University Hospital, Athens, Greece.</nlm:affiliation><country xml:lang="fr">Grèce</country><wicri:regionArea>'Attikon' University Hospital, Athens</wicri:regionArea><placeName><settlement type="city">Athènes</settlement><region nuts="2" type="region">Attique (région)</region></placeName></affiliation></author><author><name sortKey="Kaukonen, K M" sort="Kaukonen, K M" uniqKey="Kaukonen K" first="K-M" last="Kaukonen">K-M Kaukonen</name><affiliation wicri:level="3"><nlm:affiliation>Helsinki University Central Hospital, Helsinki, Finland; Australian and New Zealand Intensive Care Research Centre (ANZIC RC), Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Helsinki University Central Hospital, Helsinki, Finland; Australian and New Zealand Intensive Care Research Centre (ANZIC RC), Department of Epidemiology and Preventive Medicine, Monash University, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Koulenti, D" sort="Koulenti, D" uniqKey="Koulenti D" first="D" last="Koulenti">D. Koulenti</name><affiliation wicri:level="3"><nlm:affiliation>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; 'Attikon' University Hospital, Athens, Greece.</nlm:affiliation><country xml:lang="fr">Grèce</country><wicri:regionArea>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; 'Attikon' University Hospital, Athens</wicri:regionArea><placeName><settlement type="city">Athènes</settlement><region nuts="2" type="region">Attique (région)</region></placeName></affiliation></author><author><name sortKey="Martin, C" sort="Martin, C" uniqKey="Martin C" first="C" last="Martin">C. Martin</name><affiliation wicri:level="1"><nlm:affiliation>Hôpital Nord, Marseille, France; AzuRea Group, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Hôpital Nord, Marseille, France; AzuRea Group</wicri:regionArea><wicri:noRegion>France; AzuRea Group</wicri:noRegion><wicri:noRegion>France; AzuRea Group</wicri:noRegion></affiliation></author><author><name sortKey="Montravers, P" sort="Montravers, P" uniqKey="Montravers P" first="P" last="Montravers">P. Montravers</name><affiliation wicri:level="3"><nlm:affiliation>Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Université Paris VII, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Université Paris VII, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Rello, J" sort="Rello, J" uniqKey="Rello J" first="J" last="Rello">J. Rello</name><affiliation wicri:level="4"><nlm:affiliation>CIBERES, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>CIBERES, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region><settlement type="city">Barcelone</settlement></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author><author><name sortKey="Rhodes, A" sort="Rhodes, A" uniqKey="Rhodes A" first="A" last="Rhodes">A. Rhodes</name><affiliation wicri:level="4"><nlm:affiliation>St George's Healthcare NHS Trust and St George's University of London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>St George's Healthcare NHS Trust and St George's 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="Starr, T" sort="Starr, T" uniqKey="Starr T" first="T" last="Starr">T. 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Lipman</name><affiliation wicri:level="1"><nlm:affiliation>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Royal Brisbane and Women's Hospital, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24630304</idno><idno type="pmid">24630304</idno><idno type="doi">10.1016/j.ijantimicag.2014.01.023</idno><idno type="wicri:Area/PubMed/Corpus">003784</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003784</idno><idno type="wicri:Area/PubMed/Curation">003670</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">003670</idno><idno type="wicri:Area/PubMed/Checkpoint">003670</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">003670</idno><idno type="wicri:Area/Ncbi/Merge">001863</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: lessons from the DALI Study.</title><author><name sortKey="Roberts, J A" sort="Roberts, J A" uniqKey="Roberts J" first="J A" last="Roberts">J A Roberts</name><affiliation wicri:level="1"><nlm:affiliation>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. Electronic address: j.roberts2@uq.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Royal Brisbane and Women's Hospital, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Stove, V" sort="Stove, V" uniqKey="Stove V" first="V" last="Stove">V. Stove</name><affiliation wicri:level="1"><nlm:affiliation>Ghent University Hospital, Ghent, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Ghent University Hospital, Ghent</wicri:regionArea><wicri:noRegion>Ghent</wicri:noRegion></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>Ghent University Hospital, Ghent, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Ghent University Hospital, Ghent</wicri:regionArea><wicri:noRegion>Ghent</wicri:noRegion></affiliation></author><author><name sortKey="Sipinkoski, B" sort="Sipinkoski, B" uniqKey="Sipinkoski B" first="B" last="Sipinkoski">B. Sipinkoski</name><affiliation wicri:level="1"><nlm:affiliation>Queensland Pathology, Brisbane, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Queensland Pathology, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Mcwhinney, B" sort="Mcwhinney, B" uniqKey="Mcwhinney B" first="B" last="Mcwhinney">B. Mcwhinney</name><affiliation wicri:level="1"><nlm:affiliation>Queensland Pathology, Brisbane, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Queensland Pathology, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Ungerer, J P J" sort="Ungerer, J P J" uniqKey="Ungerer J" first="J P J" last="Ungerer">J P J. Ungerer</name><affiliation wicri:level="1"><nlm:affiliation>Queensland Pathology, Brisbane, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Queensland Pathology, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Akova, M" sort="Akova, M" uniqKey="Akova M" first="M" last="Akova">M. Akova</name><affiliation wicri:level="1"><nlm:affiliation>Hacettepe University, School of Medicine, Ankara, Turkey.</nlm:affiliation><country xml:lang="fr">Turquie</country><wicri:regionArea>Hacettepe University, School of Medicine, Ankara</wicri:regionArea><wicri:noRegion>Ankara</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>Azienda Ospedaliera-Universitaria 'Santa Maria della Misericordia', Udine, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Azienda Ospedaliera-Universitaria 'Santa Maria della Misericordia', Udine</wicri:regionArea><wicri:noRegion>Udine</wicri:noRegion></affiliation></author><author><name sortKey="Dimopoulos, G" sort="Dimopoulos, G" uniqKey="Dimopoulos G" first="G" last="Dimopoulos">G. Dimopoulos</name><affiliation wicri:level="3"><nlm:affiliation>'Attikon' University Hospital, Athens, Greece.</nlm:affiliation><country xml:lang="fr">Grèce</country><wicri:regionArea>'Attikon' University Hospital, Athens</wicri:regionArea><placeName><settlement type="city">Athènes</settlement><region nuts="2" type="region">Attique (région)</region></placeName></affiliation></author><author><name sortKey="Kaukonen, K M" sort="Kaukonen, K M" uniqKey="Kaukonen K" first="K-M" last="Kaukonen">K-M Kaukonen</name><affiliation wicri:level="3"><nlm:affiliation>Helsinki University Central Hospital, Helsinki, Finland; Australian and New Zealand Intensive Care Research Centre (ANZIC RC), Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Helsinki University Central Hospital, Helsinki, Finland; Australian and New Zealand Intensive Care Research Centre (ANZIC RC), Department of Epidemiology and Preventive Medicine, Monash University, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Koulenti, D" sort="Koulenti, D" uniqKey="Koulenti D" first="D" last="Koulenti">D. Koulenti</name><affiliation wicri:level="3"><nlm:affiliation>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; 'Attikon' University Hospital, Athens, Greece.</nlm:affiliation><country xml:lang="fr">Grèce</country><wicri:regionArea>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; 'Attikon' University Hospital, Athens</wicri:regionArea><placeName><settlement type="city">Athènes</settlement><region nuts="2" type="region">Attique (région)</region></placeName></affiliation></author><author><name sortKey="Martin, C" sort="Martin, C" uniqKey="Martin C" first="C" last="Martin">C. Martin</name><affiliation wicri:level="1"><nlm:affiliation>Hôpital Nord, Marseille, France; AzuRea Group, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Hôpital Nord, Marseille, France; AzuRea Group</wicri:regionArea><wicri:noRegion>France; AzuRea Group</wicri:noRegion><wicri:noRegion>France; AzuRea Group</wicri:noRegion></affiliation></author><author><name sortKey="Montravers, P" sort="Montravers, P" uniqKey="Montravers P" first="P" last="Montravers">P. Montravers</name><affiliation wicri:level="3"><nlm:affiliation>Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Université Paris VII, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Université Paris VII, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Rello, J" sort="Rello, J" uniqKey="Rello J" first="J" last="Rello">J. Rello</name><affiliation wicri:level="4"><nlm:affiliation>CIBERES, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>CIBERES, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region><settlement type="city">Barcelone</settlement></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author><author><name sortKey="Rhodes, A" sort="Rhodes, A" uniqKey="Rhodes A" first="A" last="Rhodes">A. Rhodes</name><affiliation wicri:level="4"><nlm:affiliation>St George's Healthcare NHS Trust and St George's University of London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>St George's Healthcare NHS Trust and St George's 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="Starr, T" sort="Starr, T" uniqKey="Starr T" first="T" last="Starr">T. Starr</name><affiliation wicri:level="1"><nlm:affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Royal Brisbane and Women's Hospital, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Wallis, S C" sort="Wallis, S C" uniqKey="Wallis S" first="S C" last="Wallis">S C Wallis</name><affiliation wicri:level="1"><nlm:affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Royal Brisbane and Women's Hospital, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Lipman, J" sort="Lipman, J" uniqKey="Lipman J" first="J" last="Lipman">J. Lipman</name><affiliation wicri:level="1"><nlm:affiliation>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Royal Brisbane and Women's Hospital, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author></analytic><series><title level="j">International journal of antimicrobial agents</title><idno type="eISSN">1872-7913</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Anti-Bacterial Agents (administration & dosage)</term><term>Anti-Bacterial Agents (metabolism)</term><term>Anti-Bacterial Agents (pharmacokinetics)</term><term>Chromatography</term><term>Critical Illness</term><term>Drug Monitoring</term><term>Female</term><term>Humans</term><term>International Cooperation</term><term>Male</term><term>Middle Aged</term><term>Plasma (chemistry)</term><term>Protein Binding</term><term>Teicoplanin (administration & dosage)</term><term>Teicoplanin (metabolism)</term><term>Teicoplanin (pharmacokinetics)</term><term>Young Adult</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Antibactériens (administration et posologie)</term><term>Antibactériens (métabolisme)</term><term>Antibactériens (pharmacocinétique)</term><term>Chromatographie</term><term>Coopération internationale</term><term>Femelle</term><term>Humains</term><term>Jeune adulte</term><term>Liaison aux protéines</term><term>Maladie grave</term><term>Mâle</term><term>Plasma sanguin ()</term><term>Sujet âgé</term><term>Surveillance pharmacologique</term><term>Téicoplanine (administration et posologie)</term><term>Téicoplanine (métabolisme)</term><term>Téicoplanine (pharmacocinétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Teicoplanin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Teicoplanin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Teicoplanin</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Antibactériens</term><term>Téicoplanine</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Plasma</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antibactériens</term><term>Téicoplanine</term></keywords><keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Antibactériens</term><term>Téicoplanine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Chromatography</term><term>Critical Illness</term><term>Drug Monitoring</term><term>Female</term><term>Humans</term><term>International Cooperation</term><term>Male</term><term>Middle Aged</term><term>Protein Binding</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Chromatographie</term><term>Coopération internationale</term><term>Femelle</term><term>Humains</term><term>Jeune adulte</term><term>Liaison aux protéines</term><term>Maladie grave</term><term>Mâle</term><term>Plasma sanguin</term><term>Sujet âgé</term><term>Surveillance pharmacologique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2-26.0) and free 1.5 (0.7-2.5); trough, total 11.9 (10.2-22.7) and free 1.8 (0.6-2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5-15.6%) and 8.2% (5.5-16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (ρ = 0.79, P = 0.0021) and trough (ρ = 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24630304</PMID><DateCreated><Year>2014</Year><Month>04</Month><Day>28</Day></DateCreated><DateCompleted><Year>2014</Year><Month>12</Month><Day>09</Day></DateCompleted><DateRevised><Year>2014</Year><Month>04</Month><Day>28</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1872-7913</ISSN><JournalIssue CitedMedium="Internet"><Volume>43</Volume><Issue>5</Issue><PubDate><Year>2014</Year><Month>May</Month></PubDate></JournalIssue><Title>International journal of antimicrobial agents</Title><ISOAbbreviation>Int. J. Antimicrob. Agents</ISOAbbreviation></Journal><ArticleTitle>Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: lessons from the DALI Study.</ArticleTitle><Pagination><MedlinePgn>423-30</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ijantimicag.2014.01.023</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0924-8579(14)00048-X</ELocationID><Abstract><AbstractText>The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2-26.0) and free 1.5 (0.7-2.5); trough, total 11.9 (10.2-22.7) and free 1.8 (0.6-2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5-15.6%) and 8.2% (5.5-16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (ρ = 0.79, P = 0.0021) and trough (ρ = 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.</AbstractText><CopyrightInformation>Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Roberts</LastName><ForeName>J A</ForeName><Initials>JA</Initials><AffiliationInfo><Affiliation>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. Electronic address: j.roberts2@uq.edu.au.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stove</LastName><ForeName>V</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Ghent University Hospital, Ghent, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>De Waele</LastName><ForeName>J J</ForeName><Initials>JJ</Initials><AffiliationInfo><Affiliation>Ghent University Hospital, Ghent, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sipinkoski</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Queensland Pathology, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McWhinney</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Queensland Pathology, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ungerer</LastName><ForeName>J P J</ForeName><Initials>JP</Initials><AffiliationInfo><Affiliation>Queensland Pathology, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Akova</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Hacettepe University, School of Medicine, Ankara, Turkey.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bassetti</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Azienda Ospedaliera-Universitaria 'Santa Maria della Misericordia', Udine, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dimopoulos</LastName><ForeName>G</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>'Attikon' University Hospital, Athens, Greece.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kaukonen</LastName><ForeName>K-M</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>Helsinki University Central Hospital, Helsinki, Finland; Australian and New Zealand Intensive Care Research Centre (ANZIC RC), Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Koulenti</LastName><ForeName>D</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; 'Attikon' University Hospital, Athens, Greece.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Martin</LastName><ForeName>C</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Hôpital Nord, Marseille, France; AzuRea Group, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Montravers</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Université Paris VII, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rello</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>CIBERES, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rhodes</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>St George's Healthcare NHS Trust and St George's University of London, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Starr</LastName><ForeName>T</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wallis</LastName><ForeName>S C</ForeName><Initials>SC</Initials><AffiliationInfo><Affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lipman</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>DALI Study Authors</CollectiveName></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016448">Multicenter Study</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>02</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Int J Antimicrob Agents</MedlineTA><NlmUniqueID>9111860</NlmUniqueID><ISSNLinking>0924-8579</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000900">Anti-Bacterial Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>61036-62-2</RegistryNumber><NameOfSubstance UI="D017334">Teicoplanin</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000900" MajorTopicYN="N">Anti-Bacterial Agents</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002845" MajorTopicYN="N">Chromatography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016638" MajorTopicYN="N">Critical Illness</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016903" MajorTopicYN="Y">Drug Monitoring</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007391" MajorTopicYN="N">International Cooperation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010949" MajorTopicYN="N">Plasma</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017334" MajorTopicYN="N">Teicoplanin</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Antibiotics</Keyword><Keyword MajorTopicYN="N">Critically ill patients</Keyword><Keyword MajorTopicYN="N">Glycopeptides</Keyword><Keyword MajorTopicYN="N">Hypoalbuminaemia</Keyword><Keyword MajorTopicYN="N">ICU</Keyword><Keyword MajorTopicYN="N">Pharmacokinetics</Keyword></KeywordList><InvestigatorList><Investigator ValidYN="Y"><LastName>Roberts</LastName><ForeName>Jason A</ForeName><Initials>JA</Initials></Investigator><Investigator ValidYN="Y"><LastName>Lipman</LastName><ForeName>Jeffrey</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Starr</LastName><ForeName>Therese</ForeName><Initials>T</Initials></Investigator><Investigator ValidYN="Y"><LastName>Wallis</LastName><ForeName>Steven C</ForeName><Initials>SC</Initials></Investigator><Investigator ValidYN="Y"><LastName>Paul</LastName><ForeName>Sanjoy</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ribas</LastName><ForeName>Antonio Margarit</ForeName><Initials>AM</Initials></Investigator><Investigator ValidYN="Y"><LastName>De Waele</LastName><ForeName>Jan J</ForeName><Initials>JJ</Initials></Investigator><Investigator ValidYN="Y"><LastName>DeCrop</LastName><ForeName>Luc</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Spapen</LastName><ForeName>Herbert</ForeName><Initials>H</Initials></Investigator><Investigator ValidYN="Y"><LastName>Wauters</LastName><ForeName>Joost</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dugernier</LastName><ForeName>Thierry</ForeName><Initials>T</Initials></Investigator><Investigator ValidYN="Y"><LastName>Jorens</LastName><ForeName>Philippe</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dapper</LastName><ForeName>Ilse</ForeName><Initials>I</Initials></Investigator><Investigator ValidYN="Y"><LastName>De Backer</LastName><ForeName>Daniel</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Taccone</LastName><ForeName>Fabio S</ForeName><Initials>FS</Initials></Investigator><Investigator ValidYN="Y"><LastName>Rello</LastName><ForeName>Jordi</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ruano</LastName><ForeName>Laura</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Afonso</LastName><ForeName>Elsa</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Alvarez-Lerma</LastName><ForeName>Francisco</ForeName><Initials>F</Initials></Investigator><Investigator ValidYN="Y"><LastName>Gracia-Arnillas</LastName><ForeName>Maria Pilar</ForeName><Initials>MP</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fernández</LastName><ForeName>Francisco</ForeName><Initials>F</Initials></Investigator><Investigator ValidYN="Y"><LastName>Feijoo</LastName><ForeName>Neus</ForeName><Initials>N</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bardolet</LastName><ForeName>Neus</ForeName><Initials>N</Initials></Investigator><Investigator ValidYN="Y"><LastName>Rovira</LastName><ForeName>Assumpta</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Garro</LastName><ForeName>Pau</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Colon</LastName><ForeName>Diana</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Castillo</LastName><ForeName>Carlos</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fernado</LastName><ForeName>Juan</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Lopez</LastName><ForeName>Maria Jesus</ForeName><Initials>MJ</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fernandez</LastName><ForeName>Jose Luis</ForeName><Initials>JL</Initials></Investigator><Investigator ValidYN="Y"><LastName>Arribas</LastName><ForeName>Ana Maria</ForeName><Initials>AM</Initials></Investigator><Investigator ValidYN="Y"><LastName>Teja</LastName><ForeName>Jose Luis</ForeName><Initials>JL</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ots</LastName><ForeName>Elsa</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Montejo</LastName><ForeName>Juan Carlos</ForeName><Initials>JC</Initials></Investigator><Investigator ValidYN="Y"><LastName>Catalan</LastName><ForeName>Mercedes</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Prieto</LastName><ForeName>Isidro</ForeName><Initials>I</Initials></Investigator><Investigator ValidYN="Y"><LastName>Gonzalo</LastName><ForeName>Gloria</ForeName><Initials>G</Initials></Investigator><Investigator ValidYN="Y"><LastName>Galvan</LastName><ForeName>Beatriz</ForeName><Initials>B</Initials></Investigator><Investigator ValidYN="Y"><LastName>Blasco</LastName><ForeName>Miguel Angel</ForeName><Initials>MA</Initials></Investigator><Investigator ValidYN="Y"><LastName>Meyer</LastName><ForeName>Estibaliz</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Nogal</LastName><ForeName>Frutos Del</ForeName><Initials>FD</Initials></Investigator><Investigator ValidYN="Y"><LastName>Vidaur</LastName><ForeName>Loreto</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Sebastian</LastName><ForeName>Rosa</ForeName><Initials>R</Initials></Investigator><Investigator ValidYN="Y"><LastName>Garde</LastName><ForeName>Pila Marco</ForeName><Initials>PM</Initials></Investigator><Investigator ValidYN="Y"><LastName>Velasco</LastName><ForeName>Maria del Mar Martin</ForeName><Initials>Mdel M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Crespo</LastName><ForeName>Rafael Zaragoza</ForeName><Initials>RZ</Initials></Investigator><Investigator ValidYN="Y"><LastName>Esperatti</LastName><ForeName>Mariano</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Torres</LastName><ForeName>Antoni</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Montravers</LastName><ForeName>Philippe</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Baldesi</LastName><ForeName>Olivier</ForeName><Initials>O</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dupont</LastName><ForeName>Herve</ForeName><Initials>H</Initials></Investigator><Investigator ValidYN="Y"><LastName>Mahjoub</LastName><ForeName>Yazine</ForeName><Initials>Y</Initials></Investigator><Investigator ValidYN="Y"><LastName>Lasocki</LastName><ForeName>Sigismond</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Constantin</LastName><ForeName>Jean Michel</ForeName><Initials>JM</Initials></Investigator><Investigator ValidYN="Y"><LastName>Payen</LastName><ForeName>Jean François</ForeName><Initials>JF</Initials></Investigator><Investigator ValidYN="Y"><LastName>Martin</LastName><ForeName>Claude</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Albanese</LastName><ForeName>Jacques</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Malledant</LastName><ForeName>Yannick</ForeName><Initials>Y</Initials></Investigator><Investigator ValidYN="Y"><LastName>Pottecher</LastName><ForeName>Julien</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Lefrant</LastName><ForeName>Jean-Yves</ForeName><Initials>JY</Initials></Investigator><Investigator ValidYN="Y"><LastName>Jaber</LastName><ForeName>Samir</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Joannes-Boyau</LastName><ForeName>Olivier</ForeName><Initials>O</Initials></Investigator><Investigator ValidYN="Y"><LastName>Orban</LastName><ForeName>Christophe</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ostermann</LastName><ForeName>Marlies</ForeName><Initials>M</Initials></Investigator><Investigator 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IdType="doi">10.1016/j.ijantimicag.2014.01.023</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Australie</li><li>Belgique</li><li>Espagne</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>Catalogne</li><li>Grand Londres</li><li>Victoria (État)</li><li>Île-de-France</li></region><settlement><li>Athènes</li><li>Barcelone</li><li>Londres</li><li>Melbourne</li><li>Paris</li></settlement><orgName><li>Université autonome de Barcelone</li><li>Université de Londres</li></orgName></list><tree><country name="Australie"><noRegion><name sortKey="Roberts, J A" sort="Roberts, J A" uniqKey="Roberts J" first="J A" last="Roberts">J A Roberts</name></noRegion><name sortKey="Kaukonen, K M" sort="Kaukonen, K M" uniqKey="Kaukonen K" first="K-M" last="Kaukonen">K-M Kaukonen</name><name sortKey="Lipman, J" sort="Lipman, J" uniqKey="Lipman J" first="J" last="Lipman">J. 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Rello</name></region></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Rhodes, A" sort="Rhodes, A" uniqKey="Rhodes A" first="A" last="Rhodes">A. Rhodes</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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