DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current -Lactam Antibiotic Doses Sufficient for Critically Ill Patients?
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ID: 299758
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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| Authors | Jason A. Roberts, Sanjoy K. Paul, Murat Akova, Matteo Bassetti, Jan J. De Waele, George Dimοpoulos, Kirsi-Maija Kaukonen, Despoina Koulenti, Claudio M. Martin, P. Montravers, Jordi Rello, Andrew Rhodes, T. Starr, S. C. Wallis, Jeffrey Lipman, Jason A. Roberts, Jeffrey Lipman, T. Starr, Steven C. Wallis, Sanjoy K. Paul, A. S. Margarit, Jan J. De Waele, Luc De Crop, Herbert Spapen, Joost Wauters, Thierry Dugernier, Philippe G. Jorens, I. Dapper, Daniel De Backer, Fabio Silvio Taccone, Jordi Rello, Laura Ruano, Elsa Afonso, Francisco Álvarez-Lerma, M.P. Gracia-Arnillas, Francisco Arnalich, Nícolas de Albuquerque Pereira Feijóo, N. Bardolet, A Rovira, Pau Garro, Diego Colón, C. Castillo, J. Fernado, María José López, José Luís Fernández, Alfredo Arribas, J. L. Teja, Elsa Ots, Juan Carlos Montejo, M. S. Catalán, I. Prieto, G. Gonzalo, Beatriz Galván, M. A. Blasco, EC Meyer, F. Del Nogal, Loreto Vidaur, Rafael Sebastián, P. M. Garde, M. d. M. Martin Velasco, Rafael Zaragoza, M. Esperatti, A. Torres, P. Montravers, Olivier Baldési, H. Dupont, Yazine Mahjoub, Sigismond Lasocki, Jean-Michel Constantin, Jean‐François Payen, Claudio M. Martin, J. Albanèse, Yannick Mallédant, Julien Pottecher, Jean Yves Lefrant, S. Jaber, O. Joannes-Boyau, Carmen Orban, Marlies Ostermann, Cathrine McKenzie, W. R. Berry, Julie Smith, K Lei, Francesca Rubulotta, Anthony Gordon, Stephen J. Brett, M. Stotz, M. Templeton, Andrew Rhodes, Claudia Ebm, Cristiane Aparecida Moran, Kirsi-Maija Kaukonen, Ville Pettilä, George Dimοpoulos, Despoina Koulenti, A. Xristodoulou, Vasiliki Theodorou, Georgios Kouliatsis, Eleni Sertaridou, George Anthopoulos |
| Journal | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America |
| Year | 2014 |
| DOI |
10.1093/cid/ciu027
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| URL | |
| Keywords | Keywords not found |
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