DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current -Lactam Antibiotic Doses Sufficient for Critically Ill Patients?
Jason A. Roberts(The University of Queensland), Sanjoy K. Paul(The University of Queensland), Murat Akova(Hacettepe University), Matteo Bassetti(Ospedale Santa Maria della Misericordia di Udine), Jan J. De Waele(Ghent University Hospital), G. Dimopoulos(University General Hospital Attikon), Kirsi-Maija Kaukonen(Helsinki University Hospital), Despoina Koulenti(The University of Queensland), Claudio M. Martin(Capital Group (United States)), P. Montravers(Université Claude Bernard Lyon 1), Jordi Rello(Universitat Autònoma de Barcelona), Andrew Rhodes(St George's, University of London), T. Starr(Royal Brisbane and Women's Hospital), S. C. Wallis(The University of Queensland), Jeffrey Lipman(The University of Queensland), DALI Study(The University of Queensland), Jason A. Roberts(The University of Queensland), Jeffrey Lipman(The University of Queensland), T. Starr(The University of Queensland), Steven C. Wallis(The University of Queensland), Sanjoy K. Paul, A. Margarit Ribas(Ghent University Hospital), Jan J. De Waele(Ghent University Hospital), Luc De Crop(The University of Queensland), Herbert Spapen(The University of Queensland), Joost Wauters(Centre Hospitalier Universitaire de Nîmes), Thierry Dugernier(The University of Queensland), Philippe G. Jorens(Centre Hospitalier Universitaire de Nîmes), I. Dapper(Centre Hospitalier Universitaire de Nîmes), Daniel De Backer, Fabio Silvio Taccone(Universitat Autònoma de Barcelona), J. Rello(Centro de Investigación en Red en Enfermedades Cardiovasculares), Laura Ruano(The University of Queensland), Elsa Afonso(The University of Queensland), Francisco Álvarez-Lerma, M.P. Gracia-Arnillas(The University of Queensland), F. Fernandez(The University of Queensland), Nícolas de Albuquerque Pereira Feijóo(The University of Queensland), N. Bardolet, A Rovira(The University of Queensland), Pau Garro(Centre Hospitalier Universitaire de Nîmes), Diego Colón(The University of Queensland), C. Castillo(The University of Queensland), J. Fernado, María José López, José Luís Fernández(The University of Queensland), Alfredo Arribas, J. L. Teja(The University of Queensland), Elsa Ots(The University of Queensland), Juan Carlos Montejo(The University of Queensland), M. S. Catalán(Centre Hospitalier Universitaire de Nîmes), I. Prieto(University General Hospital Attikon), G. Gonzalo, Beatriz Galván(The University of Queensland), M. A. Blasco(The University of Queensland), EC Meyer(The University of Queensland), F. Del Nogal(Centre Hospitalier Universitaire de Nîmes), Loreto Vidaur(The University of Queensland), Rafael Sebastián(The University of Queensland), P. M. Garde, M. d. M. Martin Velasco(The University of Queensland), Rafael Zaragoza(The University of Queensland), M. Esperatti, A. Torres(Délégation Paris 7), P. Montravers(Université Claude Bernard Lyon 1), Olivier Baldési(The University of Queensland), H. Dupont(Centre Hospitalier Universitaire de Nîmes), Yazine Mahjoub(Centre Hospitalier Universitaire de Nîmes), Sigismond Lasocki, Jean-Michel Constantin, Jean‐François Payen(Hôpital Nord), C. Martin(The University of Queensland), J. Albanèse(Centre Hospitalier Universitaire de Nîmes), Yannick Mallédant(The University of Queensland), Julien Pottecher(Centre Hospitalier Universitaire de Nîmes), Jean Yves Lefrant(Centre Hospitalier Universitaire de Nîmes), S. Jaber(St. George's University), O. Joannes-Boyau(The University of Queensland), Carmen Orban(The University of Queensland), Marlies Ostermann(The University of Queensland), Cathrine McKenzie(The University of Queensland), W. R. Berry(The University of Queensland), Julie Smith(The University of Queensland), K Lei(The University of Queensland), Francesca Rubulotta, Anthony Gordon(Centre Hospitalier Universitaire de Nîmes), Stephen J. Brett(The University of Queensland), M. Stotz(The University of Queensland), M. Templeton(St. George's University), Andrew Rhodes(The University of Queensland), Claudia Ebm(The University of Queensland), Cristiane Aparecida Moran, K.-M. Kaukonen(The University of Queensland), Ville Pettilä(University General Hospital Attikon), G. Dimopoulos(The University of Queensland), Despoina Koulenti(The University of Queensland), A. Xristodoulou(The University of Queensland), Vasiliki Theodorou(University General Hospital Attikon), Georgios Kouliatsis(The University of Queensland), Eleni Sertaridou(University General Hospital Attikon), George Anthopoulos(University General Hospital Attikon), G. Choutas(Centre Hospitalier Universitaire de Nîmes), T. Rantis(Centre Hospitalier Universitaire de Nîmes), Stylianos Karatzas(The University of Queensland), Margarita Balla(The University of Queensland), Metaxia Papanikolaou(The University of Queensland), Pavlos Myrianthefs, Alexandra Gavala(University General Hospital Attikon), G. Fildisis, Antonia Koutsoukou(The University of Queensland), Magdalini Kyriakopoulou(The University of Queensland), Kalomira Petrochilou(The University of Queensland), Maria Kompoti(The University of Queensland), Martha Michalia, F.-M. Clouva-Molyvdas(University General Hospital Attikon), George Gkiokas(The University of Queensland), F. Nikolakopoulos(The University of Queensland), V. Psychogiou(The University of Queensland), Polychronis Malliotakis(The University of Queensland), E. Akoumianaki(The University of Queensland), Emmanuel Lilitsis(The University of Queensland), Vasilios Koulouras(University General Hospital Attikon), George Nakos(The University of Queensland), Maria Kalogirou, Apostolos Komnos(Centre Hospitalier Universitaire de Nîmes), Tilemachos Zafeiridis(The University of Queensland), C. Chaintoutis(The University of Queensland), Kostoula Arvaniti(Centre Hospitalier Universitaire de Nîmes), Dimitris Matamis(The University of Queensland), C. Chaintoutis(The University of Queensland), C. Kydona(The University of Queensland), N. Gritsi-Gerogianni(Centre Hospitalier Universitaire de Nîmes), T. Giasnetsova(The University of Queensland), M. Giannakou(Centre Hospitalier Universitaire de Nîmes), Ioanna Soultati(Centre Hospitalier Universitaire de Nîmes), Ilias Chytas(The University of Queensland), E Antoniadou(The University of Queensland), E. Antipa(Centre Hospitalier Universitaire de Nîmes), Dimitrios Lathyris(Centre Hospitalier Universitaire de Nîmes), Triantafyllia Koukoubani(Centre Hospitalier Universitaire de Nîmes), Theoniki Paraforou(The University of Queensland), K. Spiropoulou(The University of Queensland), Vasileios Bekos, Alexander M. Spring(Centre Hospitalier Universitaire de Nîmes), T. Kalatzi(The University of Queensland), H. Nikolaou(The University of Queensland), M Laskou(Centre Hospitalier Universitaire de Nîmes), Ioannis Strouvalis(Centre Hospitalier Universitaire de Nîmes), Stavros Aloizos(Centre Hospitalier Universitaire de Nîmes), S. Kapogiannis(St. George's University), O. Soldatou, Matteo Bassetti(The University of Queensland), Chiara Adembri(University General Hospital Attikon), Gianluca Villa(Universitat Autònoma de Barcelona), Antonino Giarratano(Centre Hospitalier Universitaire de Nîmes), Santi Maurizio Raineri(Universitat Autònoma de Barcelona), Andrea Cortegiani(The University of Queensland), Francesca Montalto(Universitat Autònoma de Barcelona), Maria Teresa Strano, V. Marco Ranieri(The University of Queensland), Claudio Sandroni(University General Hospital Attikon), Gennaro De Pascale, Alexandre Molin(The University of Queensland), Paolo Pelosi(Centre Hospitalier Universitaire de Nîmes), L. Montagnani(The University of Queensland), Rosario Urbino(Centre Hospitalier Universitaire de Nîmes), Ilaria Mastromauro, Francesco Giuseppe De Rosa, V. Marco Ranieri(Centre Hospitalier Universitaire de Nîmes), Teresa Cardoso(Centre Hospitalier Universitaire de Nîmes), Susana Afonso(The University of Queensland), João Gonçalves-Pereira, J. P. Baptista(Hacettepe University), M. Akova(Hacettepe University), Ahmet Özveren
Cited by 1,075Open Access
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% 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. 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% 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. 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.