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DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current -Lactam Antibiotic Doses Sufficient for Critically Ill Patients?

Authors
Jason Roberts,Sanjoy Paul
Murat Akova,Matteo Bassetti,Jan Waele,George Dimοpoulos,K.-M. Kaukonen,Despoina Koulenti,Claudio Martin,P. Montravers,Jordi Rello,Andrew Rhodes,T. Starr,S. Wallis,Jeffrey Lipman,Steven Wallis,J. Ribas,Luc Crop,Herbert Spapen,Joost Wauters,Thierry Dugernier,Nina Hermans,I. Dapper,Daniel Backer,Fabio Taccone,Laura Ruano,Elsa Afonso,José Lorente,M.P. Gracia-Arnillas,Francisco Arnalich,Nícolas Feijóo,N. Bardolet,A Rovira,Pau Garro,Diego Colón,C. Castillo,J. Fernado,María López,José Fernández,Alfredo Arribas,J. Teja,Elsa Ots,Juan Montejo,M. Catalán,I. Prieto,G. Gonzalo,Beatriz Galván,María Blasco,EC Meyer,F. Nogal,Loreto Santa‐Marina,Rafael Sebastián,P. Garde,María Velasco,Rafael Zaragoza,M. Esperatti,A. Torres,Olivier Baldési,Rob Wilde,Yazine Mahjoub,Sigismond Lasocki,Jean-Michel Constantin,Jean‐François Payen,Jacques Albanèse,Yannick Mallédant,Julien Pottecher,Jean Lefrant,Martin Scharffenberg,Hervé Quintard,Carmen Orban,Marlies Ostermann,Deborah Cook,W. Berry,Julie Smith,Katie Lei,F. Rubulotta,Adrienne Gordon,Stephen Brett,Martin Stotz,Maie Templeton,Claudia Ebm,Cristiane Moran,Ville Pettilä,A. Xristodoulou,Vasiliki Theodorou,George Kouliatsis,Eleni Sertaridou,George Anthopoulos,G. Choutas,T. Rantis,Stylianos Karatzas,Margarita Balla,Metaxia Papanikolaou,Pavlos Myrianthefs,Alexandra Gavala,Antigoni Martika,A. Koutsoukou,Magdalini Kyriakopoulou,Kalomira Petrochilou,Maria Kompoti,Martha Michalia,F.-M. Clouva-Molyvdas,George Gkiokas,F. Nikolakopoulos,V. Psychogiou,Polychronis Malliotakis,E. Akoumianaki,Emmanuel Lilitsis,Vasilios Koulouras,George Nakos,Maria Kalogirou,Apostolos Komnos,Tilemachos Zafeiridis,David Carpio,Kostoula Arvaniti,D. Matamis,C. Kydona,N. Gritsi-Gerogianni,T. Giasnetsova,Savvoula Savvidou,Ioanna Soultati,Ilias Chytas,E Antoniadou,E. Antipa,Dimitrios Lathyris,Triantafyllia Koukoubani,Theoniki Paraforou,K. Spiropoulou,Vasileios Bekos,Alexander Spring,T. Kalatzi,H Nikolaou,M Laskou,Ioannis Strouvalis,Stavros Aloizos,S. Kapogiannis,O. Soldatou,Chiara Adembri,Giovanni Villa,Antonino Giarratano,Santi Raineri,Andrea Cortegiani,Francesca Montalto,Maria Strano,Marco Maggiorini,Claudio Sandroni,Gennaro Pascale,Pierpaolo Terragni,Paolo Pelosi,Goffredina Spanò,Rosario Urbino,Ilaria Mastromauro,Francesco Rosa,Teresa Cardoso,Susana Afonso,João Gonçalves-Pereira,Parjam Zolfaghari,Ahmet Özveren,E. Meyer
+157 authors
,Alain Rudiger
Published
Jan 14, 2014
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Abstract

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.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% f T>MIC) 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.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% f T>MIC and 100% f T>MIC ratios (OR, 1.02 and 1.56, respectively; P < .03), with significant interaction with sickness severity status.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.

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