DALI: Defining antibiotic levels in intensive care unit patients: Are current ß-lactam antibiotic doses sufficient for critically ill patients?

Jason A. Roberts, Sanjoy K. Paul, Murat Akova, Matteo Bassetti, Jan J. De Waele, George Dimopoulos, Kirsi Maija Kaukonen, Despoina Koulenti, Claude Martin, Philippe Montravers, Jordi Rello, Andrew Rhodes, Therese Starr, Steven C. Wallis, Jeffrey Lipman, Antonio Margarit Ribas, Luc De Crop, Herbert Spapen, Joost Wauters, Thierry DugernierPhilippe Jorens, Ilse Dapper, Daniel De Backer, Fabio S. Taccone, Laura Ruano, Elsa Afonso, Francisco Alvarez-Lerma, Maria Pilar Gracia-Arnillas, Francisco Fernández, Neus Feijoo, Neus Bardolet, Assumpta Rovira, Pau Garro, Diana Colon, Carlos Castillo, Juan Fernado, Maria Jesus Lopez, Jose Luis Fernandez, Ana Maria Arribas, Jose Luis Teja, Elsa Ots, Juan Carlos Montejo, Mercedes Catalan, Isidro Prieto, Gloria Gonzalo, Beatriz Galvan, Miguel Angel Blasco, Estibaliz Meyer, Frutos Del Nogal, Loreto Vidaur, Rosa Sebastian, Pila Marco Garde, Maria Del Mar Martin Velasco, Rafael Zaragoza Crespo, Mariano Esperatti, Antoni Torres, Olivier Baldesi, Herve Dupont, Yazine Mahjoub, Sigismond Lasocki, Jean Michel Constantin, Jean François Payen, Jacques Albanese, Yannick Malledant, Julien Pottecher, Jean Yves Lefrant, Samir Jaber, Olivier Joannes-Boyau, Christophe Orban, Marlies Ostermann, Cathrine McKenzie, William Berry, John Smith, Katie Lei, Francesca Rubulotta, Anthony Gordon, Stephen Brett, Martin Stotz, Maie Templeton, Claudia Ebm, Carl Moran, Ville Pettilä, Aglaia Xristodoulou, Vassiliki Theodorou, Georgios Kouliatsis, Eleni Sertaridou, Georgios Anthopoulos, George Choutas, Thanos Rantis, Stylianos Karatzas, Margarita Balla, Metaxia Papanikolaou, Pavlos Myrianthefs, Alexandra Gavala, Georgios Fildisis, Antonia Koutsoukou, Magdalini Kyriakopoulou, Kalomoira Petrochilou, Maria Kompoti, Martha Michalia, Fillis Maria Clouva-Molyvdas, Georgios Gkiokas, Fotios Nikolakopoulos, Vasiliki Psychogiou, Polychronis Malliotakis, Evangelia Akoumianaki, Emmanouil Lilitsis, Vassilios Koulouras, George Nakos, Mihalis Kalogirou, Apostolos Komnos, Tilemachos Zafeiridis, Christos Chaintoutis, Kostoula Arvaniti, Dimitrios Matamis, Christina Kydona, Nikoleta Gritsi-Gerogianni, Tatiana Giasnetsova, Maria Giannakou, Ioanna Soultati, Ilias Chytas, Eleni Antoniadou, Elli Antipa, Dimitrios Lathyris, Triantafyllia Koukoubani, Theoniki Paraforou, Kyriaki Spiropoulou, Vasileios Bekos, Anna Spring, Theodora Kalatzi, Hara Nikolaou, Maria Laskou, Ioannis Strouvalis, Stavros Aloizos, Spyridon Kapogiannis, Ourania Soldatou, Chiara Adembri, Gianluca Villa, Antonio Giarratano, Santi Maurizio Raineri, Andrea Cortegiani, Francesca Montalto, Maria Teresa Strano, V. Marco Ranieri, Claudio Sandroni, Gennaro De Pascale, Alexandre Molin, Paolo Pelosi, Luca Montagnani, Rosario Urbino, Ilaria Mastromauro, Francesco G. De Rosa, Teresa Cardoso, Susana Afonso, João Gonçalves-Pereira, João Pedro Baptista, Arife Özveren

Research output: Contribution to journalArticle

Abstract

Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether α-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 α-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% f TMIC) and 100% (100% f T 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 TMIC 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% f TMIC and 100% f TMIC ratios (OR, 1.02 and 1.56, respectively; P

Original languageEnglish (US)
Pages (from-to)1072-1083
Number of pages12
JournalClinical Infectious Diseases
Volume58
Issue number8
DOIs
StatePublished - Apr 15 2014
Externally publishedYes

Fingerprint

Lactams
Critical Illness
Intensive Care Units
Anti-Bacterial Agents
Microbial Sensitivity Tests
Pharmacokinetics
Odds Ratio
APACHE
Infection
Cross-Sectional Studies
Logistic Models
Morbidity
Delivery of Health Care

Keywords

  • adverse events
  • continuous infusion
  • extended infusion
  • pharmacodynamics
  • pharmacokinetics

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)
  • Medicine(all)

Cite this

DALI : Defining antibiotic levels in intensive care unit patients: Are current ß-lactam antibiotic doses sufficient for critically ill patients? / Roberts, Jason A.; Paul, Sanjoy K.; Akova, Murat; Bassetti, Matteo; De Waele, Jan J.; Dimopoulos, George; Kaukonen, Kirsi Maija; Koulenti, Despoina; Martin, Claude; Montravers, Philippe; Rello, Jordi; Rhodes, Andrew; Starr, Therese; Wallis, Steven C.; Lipman, Jeffrey; Margarit Ribas, Antonio; De Crop, Luc; Spapen, Herbert; Wauters, Joost; Dugernier, Thierry; Jorens, Philippe; Dapper, Ilse; De Backer, Daniel; Taccone, Fabio S.; Ruano, Laura; Afonso, Elsa; Alvarez-Lerma, Francisco; Gracia-Arnillas, Maria Pilar; Fernández, Francisco; Feijoo, Neus; Bardolet, Neus; Rovira, Assumpta; Garro, Pau; Colon, Diana; Castillo, Carlos; Fernado, Juan; Lopez, Maria Jesus; Fernandez, Jose Luis; Arribas, Ana Maria; Teja, Jose Luis; Ots, Elsa; Carlos Montejo, Juan; Catalan, Mercedes; Prieto, Isidro; Gonzalo, Gloria; Galvan, Beatriz; Blasco, Miguel Angel; Meyer, Estibaliz; Del Nogal, Frutos; Vidaur, Loreto; Sebastian, Rosa; Garde, Pila Marco; Martin Velasco, Maria Del Mar; Zaragoza Crespo, Rafael; Esperatti, Mariano; Torres, Antoni; Baldesi, Olivier; Dupont, Herve; Mahjoub, Yazine; Lasocki, Sigismond; Constantin, Jean Michel; Payen, Jean François; Albanese, Jacques; Malledant, Yannick; Pottecher, Julien; Lefrant, Jean Yves; Jaber, Samir; Joannes-Boyau, Olivier; Orban, Christophe; Ostermann, Marlies; McKenzie, Cathrine; Berry, William; Smith, John; Lei, Katie; Rubulotta, Francesca; Gordon, Anthony; Brett, Stephen; Stotz, Martin; Templeton, Maie; Ebm, Claudia; Moran, Carl; Pettilä, Ville; Xristodoulou, Aglaia; Theodorou, Vassiliki; Kouliatsis, Georgios; Sertaridou, Eleni; Anthopoulos, Georgios; Choutas, George; Rantis, Thanos; Karatzas, Stylianos; Balla, Margarita; Papanikolaou, Metaxia; Myrianthefs, Pavlos; Gavala, Alexandra; Fildisis, Georgios; Koutsoukou, Antonia; Kyriakopoulou, Magdalini; Petrochilou, Kalomoira; Kompoti, Maria; Michalia, Martha; Clouva-Molyvdas, Fillis Maria; Gkiokas, Georgios; Nikolakopoulos, Fotios; Psychogiou, Vasiliki; Malliotakis, Polychronis; Akoumianaki, Evangelia; Lilitsis, Emmanouil; Koulouras, Vassilios; Nakos, George; Kalogirou, Mihalis; Komnos, Apostolos; Zafeiridis, Tilemachos; Chaintoutis, Christos; Arvaniti, Kostoula; Matamis, Dimitrios; Kydona, Christina; Gritsi-Gerogianni, Nikoleta; Giasnetsova, Tatiana; Giannakou, Maria; Soultati, Ioanna; Chytas, Ilias; Antoniadou, Eleni; Antipa, Elli; Lathyris, Dimitrios; Koukoubani, Triantafyllia; Paraforou, Theoniki; Spiropoulou, Kyriaki; Bekos, Vasileios; Spring, Anna; Kalatzi, Theodora; Nikolaou, Hara; Laskou, Maria; Strouvalis, Ioannis; Aloizos, Stavros; Kapogiannis, Spyridon; Soldatou, Ourania; Adembri, Chiara; Villa, Gianluca; Giarratano, Antonio; Maurizio Raineri, Santi; Cortegiani, Andrea; Montalto, Francesca; Strano, Maria Teresa; Ranieri, V. Marco; Sandroni, Claudio; De Pascale, Gennaro; Molin, Alexandre; Pelosi, Paolo; Montagnani, Luca; Urbino, Rosario; Mastromauro, Ilaria; De Rosa, Francesco G.; Cardoso, Teresa; Afonso, Susana; Gonçalves-Pereira, João; Baptista, João Pedro; Özveren, Arife.

In: Clinical Infectious Diseases, Vol. 58, No. 8, 15.04.2014, p. 1072-1083.

Research output: Contribution to journalArticle

Roberts, JA, Paul, SK, Akova, M, Bassetti, M, De Waele, JJ, Dimopoulos, G, Kaukonen, KM, Koulenti, D, Martin, C, Montravers, P, Rello, J, Rhodes, A, Starr, T, Wallis, SC, Lipman, J, Margarit Ribas, A, De Crop, L, Spapen, H, Wauters, J, Dugernier, T, Jorens, P, Dapper, I, De Backer, D, Taccone, FS, Ruano, L, Afonso, E, Alvarez-Lerma, F, Gracia-Arnillas, MP, Fernández, F, Feijoo, N, Bardolet, N, Rovira, A, Garro, P, Colon, D, Castillo, C, Fernado, J, Lopez, MJ, Fernandez, JL, Arribas, AM, Teja, JL, Ots, E, Carlos Montejo, J, Catalan, M, Prieto, I, Gonzalo, G, Galvan, B, Blasco, MA, Meyer, E, Del Nogal, F, Vidaur, L, Sebastian, R, Garde, PM, Martin Velasco, MDM, Zaragoza Crespo, R, Esperatti, M, Torres, A, Baldesi, O, Dupont, H, Mahjoub, Y, Lasocki, S, Constantin, JM, Payen, JF, Albanese, J, Malledant, Y, Pottecher, J, Lefrant, JY, Jaber, S, Joannes-Boyau, O, Orban, C, Ostermann, M, McKenzie, C, Berry, W, Smith, J, Lei, K, Rubulotta, F, Gordon, A, Brett, S, Stotz, M, Templeton, M, Ebm, C, Moran, C, Pettilä, V, Xristodoulou, A, Theodorou, V, Kouliatsis, G, Sertaridou, E, Anthopoulos, G, Choutas, G, Rantis, T, Karatzas, S, Balla, M, Papanikolaou, M, Myrianthefs, P, Gavala, A, Fildisis, G, Koutsoukou, A, Kyriakopoulou, M, Petrochilou, K, Kompoti, M, Michalia, M, Clouva-Molyvdas, FM, Gkiokas, G, Nikolakopoulos, F, Psychogiou, V, Malliotakis, P, Akoumianaki, E, Lilitsis, E, Koulouras, V, Nakos, G, Kalogirou, M, Komnos, A, Zafeiridis, T, Chaintoutis, C, Arvaniti, K, Matamis, D, Kydona, C, Gritsi-Gerogianni, N, Giasnetsova, T, Giannakou, M, Soultati, I, Chytas, I, Antoniadou, E, Antipa, E, Lathyris, D, Koukoubani, T, Paraforou, T, Spiropoulou, K, Bekos, V, Spring, A, Kalatzi, T, Nikolaou, H, Laskou, M, Strouvalis, I, Aloizos, S, Kapogiannis, S, Soldatou, O, Adembri, C, Villa, G, Giarratano, A, Maurizio Raineri, S, Cortegiani, A, Montalto, F, Strano, MT, Ranieri, VM, Sandroni, C, De Pascale, G, Molin, A, Pelosi, P, Montagnani, L, Urbino, R, Mastromauro, I, De Rosa, FG, Cardoso, T, Afonso, S, Gonçalves-Pereira, J, Baptista, JP & Özveren, A 2014, 'DALI: Defining antibiotic levels in intensive care unit patients: Are current ß-lactam antibiotic doses sufficient for critically ill patients?', Clinical Infectious Diseases, vol. 58, no. 8, pp. 1072-1083. https://doi.org/10.1093/cid/ciu027
Roberts, Jason A. ; Paul, Sanjoy K. ; Akova, Murat ; Bassetti, Matteo ; De Waele, Jan J. ; Dimopoulos, George ; Kaukonen, Kirsi Maija ; Koulenti, Despoina ; Martin, Claude ; Montravers, Philippe ; Rello, Jordi ; Rhodes, Andrew ; Starr, Therese ; Wallis, Steven C. ; Lipman, Jeffrey ; Margarit Ribas, Antonio ; De Crop, Luc ; Spapen, Herbert ; Wauters, Joost ; Dugernier, Thierry ; Jorens, Philippe ; Dapper, Ilse ; De Backer, Daniel ; Taccone, Fabio S. ; Ruano, Laura ; Afonso, Elsa ; Alvarez-Lerma, Francisco ; Gracia-Arnillas, Maria Pilar ; Fernández, Francisco ; Feijoo, Neus ; Bardolet, Neus ; Rovira, Assumpta ; Garro, Pau ; Colon, Diana ; Castillo, Carlos ; Fernado, Juan ; Lopez, Maria Jesus ; Fernandez, Jose Luis ; Arribas, Ana Maria ; Teja, Jose Luis ; Ots, Elsa ; Carlos Montejo, Juan ; Catalan, Mercedes ; Prieto, Isidro ; Gonzalo, Gloria ; Galvan, Beatriz ; Blasco, Miguel Angel ; Meyer, Estibaliz ; Del Nogal, Frutos ; Vidaur, Loreto ; Sebastian, Rosa ; Garde, Pila Marco ; Martin Velasco, Maria Del Mar ; Zaragoza Crespo, Rafael ; Esperatti, Mariano ; Torres, Antoni ; Baldesi, Olivier ; Dupont, Herve ; Mahjoub, Yazine ; Lasocki, Sigismond ; Constantin, Jean Michel ; Payen, Jean François ; Albanese, Jacques ; Malledant, Yannick ; Pottecher, Julien ; Lefrant, Jean Yves ; Jaber, Samir ; Joannes-Boyau, Olivier ; Orban, Christophe ; Ostermann, Marlies ; McKenzie, Cathrine ; Berry, William ; Smith, John ; Lei, Katie ; Rubulotta, Francesca ; Gordon, Anthony ; Brett, Stephen ; Stotz, Martin ; Templeton, Maie ; Ebm, Claudia ; Moran, Carl ; Pettilä, Ville ; Xristodoulou, Aglaia ; Theodorou, Vassiliki ; Kouliatsis, Georgios ; Sertaridou, Eleni ; Anthopoulos, Georgios ; Choutas, George ; Rantis, Thanos ; Karatzas, Stylianos ; Balla, Margarita ; Papanikolaou, Metaxia ; Myrianthefs, Pavlos ; Gavala, Alexandra ; Fildisis, Georgios ; Koutsoukou, Antonia ; Kyriakopoulou, Magdalini ; Petrochilou, Kalomoira ; Kompoti, Maria ; Michalia, Martha ; Clouva-Molyvdas, Fillis Maria ; Gkiokas, Georgios ; Nikolakopoulos, Fotios ; Psychogiou, Vasiliki ; Malliotakis, Polychronis ; Akoumianaki, Evangelia ; Lilitsis, Emmanouil ; Koulouras, Vassilios ; Nakos, George ; Kalogirou, Mihalis ; Komnos, Apostolos ; Zafeiridis, Tilemachos ; Chaintoutis, Christos ; Arvaniti, Kostoula ; Matamis, Dimitrios ; Kydona, Christina ; Gritsi-Gerogianni, Nikoleta ; Giasnetsova, Tatiana ; Giannakou, Maria ; Soultati, Ioanna ; Chytas, Ilias ; Antoniadou, Eleni ; Antipa, Elli ; Lathyris, Dimitrios ; Koukoubani, Triantafyllia ; Paraforou, Theoniki ; Spiropoulou, Kyriaki ; Bekos, Vasileios ; Spring, Anna ; Kalatzi, Theodora ; Nikolaou, Hara ; Laskou, Maria ; Strouvalis, Ioannis ; Aloizos, Stavros ; Kapogiannis, Spyridon ; Soldatou, Ourania ; Adembri, Chiara ; Villa, Gianluca ; Giarratano, Antonio ; Maurizio Raineri, Santi ; Cortegiani, Andrea ; Montalto, Francesca ; Strano, Maria Teresa ; Ranieri, V. Marco ; Sandroni, Claudio ; De Pascale, Gennaro ; Molin, Alexandre ; Pelosi, Paolo ; Montagnani, Luca ; Urbino, Rosario ; Mastromauro, Ilaria ; De Rosa, Francesco G. ; Cardoso, Teresa ; Afonso, Susana ; Gonçalves-Pereira, João ; Baptista, João Pedro ; Özveren, Arife. / DALI : Defining antibiotic levels in intensive care unit patients: Are current ß-lactam antibiotic doses sufficient for critically ill patients?. In: Clinical Infectious Diseases. 2014 ; Vol. 58, No. 8. pp. 1072-1083.
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title = "DALI: Defining antibiotic levels in intensive care unit patients: Are current {\ss}-lactam antibiotic doses sufficient for critically ill patients?",
abstract = "Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether α-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 α-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{\%} f TMIC) and 100{\%} (100{\%} f T 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 TMIC 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{\%} f TMIC and 100{\%} f TMIC ratios (OR, 1.02 and 1.56, respectively; P",
keywords = "adverse events, continuous infusion, extended infusion, pharmacodynamics, pharmacokinetics",
author = "Roberts, {Jason A.} and Paul, {Sanjoy K.} and Murat Akova and Matteo Bassetti and {De Waele}, {Jan J.} and George Dimopoulos and Kaukonen, {Kirsi Maija} and Despoina Koulenti and Claude Martin and Philippe Montravers and Jordi Rello and Andrew Rhodes and Therese Starr and Wallis, {Steven C.} and Jeffrey Lipman and {Margarit Ribas}, Antonio and {De Crop}, Luc and Herbert Spapen and Joost Wauters and Thierry Dugernier and Philippe Jorens and Ilse Dapper and {De Backer}, Daniel and Taccone, {Fabio S.} and Laura Ruano and Elsa Afonso and Francisco Alvarez-Lerma and Gracia-Arnillas, {Maria Pilar} and Francisco Fern{\'a}ndez and Neus Feijoo and Neus Bardolet and Assumpta Rovira and Pau Garro and Diana Colon and Carlos Castillo and Juan Fernado and Lopez, {Maria Jesus} and Fernandez, {Jose Luis} and Arribas, {Ana Maria} and Teja, {Jose Luis} and Elsa Ots and {Carlos Montejo}, Juan and Mercedes Catalan and Isidro Prieto and Gloria Gonzalo and Beatriz Galvan and Blasco, {Miguel Angel} and Estibaliz Meyer and {Del Nogal}, Frutos and Loreto Vidaur and Rosa Sebastian and Garde, {Pila Marco} and {Martin Velasco}, {Maria Del Mar} and {Zaragoza Crespo}, Rafael and Mariano Esperatti and Antoni Torres and Olivier Baldesi and Herve Dupont and Yazine Mahjoub and Sigismond Lasocki and Constantin, {Jean Michel} and Payen, {Jean Fran{\cc}ois} and Jacques Albanese and Yannick Malledant and Julien Pottecher and Lefrant, {Jean Yves} and Samir Jaber and Olivier Joannes-Boyau and Christophe Orban and Marlies Ostermann and Cathrine McKenzie and William Berry and John Smith and Katie Lei and Francesca Rubulotta and Anthony Gordon and Stephen Brett and Martin Stotz and Maie Templeton and Claudia Ebm and Carl Moran and Ville Pettil{\"a} and Aglaia Xristodoulou and Vassiliki Theodorou and Georgios Kouliatsis and Eleni Sertaridou and Georgios Anthopoulos and George Choutas and Thanos Rantis and Stylianos Karatzas and Margarita Balla and Metaxia Papanikolaou and Pavlos Myrianthefs and Alexandra Gavala and Georgios Fildisis and Antonia Koutsoukou and Magdalini Kyriakopoulou and Kalomoira Petrochilou and Maria Kompoti and Martha Michalia and Clouva-Molyvdas, {Fillis Maria} and Georgios Gkiokas and Fotios Nikolakopoulos and Vasiliki Psychogiou and Polychronis Malliotakis and Evangelia Akoumianaki and Emmanouil Lilitsis and Vassilios Koulouras and George Nakos and Mihalis Kalogirou and Apostolos Komnos and Tilemachos Zafeiridis and Christos Chaintoutis and Kostoula Arvaniti and Dimitrios Matamis and Christina Kydona and Nikoleta Gritsi-Gerogianni and Tatiana Giasnetsova and Maria Giannakou and Ioanna Soultati and Ilias Chytas and Eleni Antoniadou and Elli Antipa and Dimitrios Lathyris and Triantafyllia Koukoubani and Theoniki Paraforou and Kyriaki Spiropoulou and Vasileios Bekos and Anna Spring and Theodora Kalatzi and Hara Nikolaou and Maria Laskou and Ioannis Strouvalis and Stavros Aloizos and Spyridon Kapogiannis and Ourania Soldatou and Chiara Adembri and Gianluca Villa and Antonio Giarratano and {Maurizio Raineri}, Santi and Andrea Cortegiani and Francesca Montalto and Strano, {Maria Teresa} and Ranieri, {V. Marco} and Claudio Sandroni and {De Pascale}, Gennaro and Alexandre Molin and Paolo Pelosi and Luca Montagnani and Rosario Urbino and Ilaria Mastromauro and {De Rosa}, {Francesco G.} and Teresa Cardoso and Susana Afonso and Jo{\~a}o Gon{\cc}alves-Pereira and Baptista, {Jo{\~a}o Pedro} and Arife {\"O}zveren",
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month = "4",
day = "15",
doi = "10.1093/cid/ciu027",
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volume = "58",
pages = "1072--1083",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "8",

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TY - JOUR

T1 - DALI

T2 - Defining antibiotic levels in intensive care unit patients: Are current ß-lactam antibiotic doses sufficient for critically ill patients?

AU - Roberts, Jason A.

AU - Paul, Sanjoy K.

AU - Akova, Murat

AU - Bassetti, Matteo

AU - De Waele, Jan J.

AU - Dimopoulos, George

AU - Kaukonen, Kirsi Maija

AU - Koulenti, Despoina

AU - Martin, Claude

AU - Montravers, Philippe

AU - Rello, Jordi

AU - Rhodes, Andrew

AU - Starr, Therese

AU - Wallis, Steven C.

AU - Lipman, Jeffrey

AU - Margarit Ribas, Antonio

AU - De Crop, Luc

AU - Spapen, Herbert

AU - Wauters, Joost

AU - Dugernier, Thierry

AU - Jorens, Philippe

AU - Dapper, Ilse

AU - De Backer, Daniel

AU - Taccone, Fabio S.

AU - Ruano, Laura

AU - Afonso, Elsa

AU - Alvarez-Lerma, Francisco

AU - Gracia-Arnillas, Maria Pilar

AU - Fernández, Francisco

AU - Feijoo, Neus

AU - Bardolet, Neus

AU - Rovira, Assumpta

AU - Garro, Pau

AU - Colon, Diana

AU - Castillo, Carlos

AU - Fernado, Juan

AU - Lopez, Maria Jesus

AU - Fernandez, Jose Luis

AU - Arribas, Ana Maria

AU - Teja, Jose Luis

AU - Ots, Elsa

AU - Carlos Montejo, Juan

AU - Catalan, Mercedes

AU - Prieto, Isidro

AU - Gonzalo, Gloria

AU - Galvan, Beatriz

AU - Blasco, Miguel Angel

AU - Meyer, Estibaliz

AU - Del Nogal, Frutos

AU - Vidaur, Loreto

AU - Sebastian, Rosa

AU - Garde, Pila Marco

AU - Martin Velasco, Maria Del Mar

AU - Zaragoza Crespo, Rafael

AU - Esperatti, Mariano

AU - Torres, Antoni

AU - Baldesi, Olivier

AU - Dupont, Herve

AU - Mahjoub, Yazine

AU - Lasocki, Sigismond

AU - Constantin, Jean Michel

AU - Payen, Jean François

AU - Albanese, Jacques

AU - Malledant, Yannick

AU - Pottecher, Julien

AU - Lefrant, Jean Yves

AU - Jaber, Samir

AU - Joannes-Boyau, Olivier

AU - Orban, Christophe

AU - Ostermann, Marlies

AU - McKenzie, Cathrine

AU - Berry, William

AU - Smith, John

AU - Lei, Katie

AU - Rubulotta, Francesca

AU - Gordon, Anthony

AU - Brett, Stephen

AU - Stotz, Martin

AU - Templeton, Maie

AU - Ebm, Claudia

AU - Moran, Carl

AU - Pettilä, Ville

AU - Xristodoulou, Aglaia

AU - Theodorou, Vassiliki

AU - Kouliatsis, Georgios

AU - Sertaridou, Eleni

AU - Anthopoulos, Georgios

AU - Choutas, George

AU - Rantis, Thanos

AU - Karatzas, Stylianos

AU - Balla, Margarita

AU - Papanikolaou, Metaxia

AU - Myrianthefs, Pavlos

AU - Gavala, Alexandra

AU - Fildisis, Georgios

AU - Koutsoukou, Antonia

AU - Kyriakopoulou, Magdalini

AU - Petrochilou, Kalomoira

AU - Kompoti, Maria

AU - Michalia, Martha

AU - Clouva-Molyvdas, Fillis Maria

AU - Gkiokas, Georgios

AU - Nikolakopoulos, Fotios

AU - Psychogiou, Vasiliki

AU - Malliotakis, Polychronis

AU - Akoumianaki, Evangelia

AU - Lilitsis, Emmanouil

AU - Koulouras, Vassilios

AU - Nakos, George

AU - Kalogirou, Mihalis

AU - Komnos, Apostolos

AU - Zafeiridis, Tilemachos

AU - Chaintoutis, Christos

AU - Arvaniti, Kostoula

AU - Matamis, Dimitrios

AU - Kydona, Christina

AU - Gritsi-Gerogianni, Nikoleta

AU - Giasnetsova, Tatiana

AU - Giannakou, Maria

AU - Soultati, Ioanna

AU - Chytas, Ilias

AU - Antoniadou, Eleni

AU - Antipa, Elli

AU - Lathyris, Dimitrios

AU - Koukoubani, Triantafyllia

AU - Paraforou, Theoniki

AU - Spiropoulou, Kyriaki

AU - Bekos, Vasileios

AU - Spring, Anna

AU - Kalatzi, Theodora

AU - Nikolaou, Hara

AU - Laskou, Maria

AU - Strouvalis, Ioannis

AU - Aloizos, Stavros

AU - Kapogiannis, Spyridon

AU - Soldatou, Ourania

AU - Adembri, Chiara

AU - Villa, Gianluca

AU - Giarratano, Antonio

AU - Maurizio Raineri, Santi

AU - Cortegiani, Andrea

AU - Montalto, Francesca

AU - Strano, Maria Teresa

AU - Ranieri, V. Marco

AU - Sandroni, Claudio

AU - De Pascale, Gennaro

AU - Molin, Alexandre

AU - Pelosi, Paolo

AU - Montagnani, Luca

AU - Urbino, Rosario

AU - Mastromauro, Ilaria

AU - De Rosa, Francesco G.

AU - Cardoso, Teresa

AU - Afonso, Susana

AU - Gonçalves-Pereira, João

AU - Baptista, João Pedro

AU - Özveren, Arife

PY - 2014/4/15

Y1 - 2014/4/15

N2 - Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether α-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 α-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% f TMIC) and 100% (100% f T 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 TMIC 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% f TMIC and 100% f TMIC ratios (OR, 1.02 and 1.56, respectively; P

AB - Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether α-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 α-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% f TMIC) and 100% (100% f T 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 TMIC 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% f TMIC and 100% f TMIC ratios (OR, 1.02 and 1.56, respectively; P

KW - adverse events

KW - continuous infusion

KW - extended infusion

KW - pharmacodynamics

KW - pharmacokinetics

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U2 - 10.1093/cid/ciu027

DO - 10.1093/cid/ciu027

M3 - Article

C2 - 24429437

AN - SCOPUS:84897414453

VL - 58

SP - 1072

EP - 1083

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 8

ER -