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

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486 Citations (Scopus)


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 <. 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. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Original languageEnglish
Pages (from-to)1072-1083
JournalClinical Infectious Diseases
Issue number8
Publication statusPublished - 15 Apr 2014


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


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