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

2014; Oxford University Press; Volume: 58; Issue: 8 Linguagem: Inglês

10.1093/cid/ciu027

1537-6591

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, G. Choutas, T. Rantis, Stylianos Karatzas, Margarita Balla, Metaxia Papanikolaou, Pavlos Myrianthefs, Alexandra Gavala, G. Fildisis, Antonia 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, C. Chaintoutis, Kostoula Arvaniti, Dimitris Matamis, C. Chaintoutis, C. Kydona, N. Gritsi-Gerogianni, T. Giasnetsova, M. Giannakou, Ioanna Soultati, Ilias Chytas, E Antoniadou, E. Antipa, Dimitrios Lathyris, Triantafyllia Koukoubani, Theoniki Paraforou, K. Spiropoulou, Vasileios Bekos, Alexander M. Spring, T. Kalatzi, H. Nikolaou, M Laskou, Ioannis Strouvalis, Stavros Aloizos, S. Kapogiannis, O. Soldatou, Matteo Bassetti, Chiara Adembri, Gianluca Villa, Antonino Giarratano, Santi Maurizio Raineri, Andrea Cortegiani, Francesca Montalto, Maria Teresa Strano, V. Marco Ranieri, Claudio Sandroni, Gennaro De Pascale, Alexandre Molin, Paolo Pelosi, L. Montagnani, Rosario Urbino, Ilaria Mastromauro, Francesco Giuseppe De Rosa, V. Marco Ranieri, Teresa Cardoso, Susana Afonso, João Gonçalves-Pereira, J. P. Baptista, Murat Akova, Ahmet Özveren,

Pneumonia and Respiratory Infections

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.