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

作者：Jason A. Roberts, J.A. Roberts, S. K. Paul, M. Akova, M. Bassetti, J.J. De Waele, G Dimopoulos, K.-M. Kaukonen, Despoina Koulenti, C. Martin, P. Montravers, J. Rello, A. Rhodes, T. Starr, S.C. Wallis, J. Lipman, DALI Study, J.A. Roberts, J.A. Roberts, J. Lipman, T. Starr, S.C. Wallis, S. K. Paul, A. Margarit Ribas, J.J. De Waele, L. De Crop, H. Spapen, J. Wauters, T. Dugernier, P. Jorens, I. Dapper, D. De Backer, F. S. Taccone, J. Rello, L. Ruano, E. Afonso, F. Álvarez-Lerma, M. P. Gracia-Arnillas, F. Fernandez, N. Feijoo, N. Bardolet, A. Rovira, P. Garro, D. Colon, C. Castillo, J. Fernado, M.J. López, J. L. Fernandez, A. M. Arribas, J.L. Teja, E. Ots, J.C. Montejo, M. Catalan, I. Prieto, G. Gonzalo, B. Galvan, M. A. Blasco, E. Meyer, F. Del Nogal, L. Vidaur, R. Sebastian, P. M. Garde, M. d. M. Martin Velasco, R. Zaragoza Crespo, M. Esperatti, A. Torres, P. Montravers, O. Baldesi, H. Dupont, Y Mahjoub, S. Lasocki, J.-M. Constantin, J. F. Payen, C. Martin, J. Albanese, Y. Mallédant, J. Pottecher, J.-Y. Lefrant, S. Jaber, O. Joannes-Boyau, C. Orban, M. Ostermann, C. McKenzie, W. Berry, J. Smith, K. Lei, F. Rubulotta, A. Gordon, S. Brett, M. Stotz, M. Templeton, A. Rhodes, C. Ebm, C Moran, K.-M. Kaukonen, V. Pettila, G Dimopoulos, Despoina Koulenti, A. Xristodoulou, V. Theodorou, G. Kouliatsis, E. Sertaridou, G. Anthopoulos, G. Choutas, T. Rantis, S. Karatzas, M. Balla, M. Papanikolaou, P. Myrianthefs, A. Gavala, G. Fildisis, A. Koutsoukou, M. Kyriakopoulou, K. Petrochilou, M. Kompoti, M. Michalia, F.-M. Clouva-Molyvdas, G. Gkiokas, F. Nikolakopoulos, Vasiliki Psychogiou, P. Malliotakis, E. Akoumianaki, E. Lilitsis, V. Koulouras, G. Nakos, Mihalis Kalogirou, A. Komnos, T. Zafeiridis, C. Chaintoutis, K. Arvaniti, D. Matamis, C. Chaintoutis, C. Kydona, N. Gritsi-Gerogianni, T. Giasnetsova, M. Giannakou, I. Soultati, I. Chytas, E. Antoniadou, E. Antipa, D. Lathyris, T. Koukoubani, T. Paraforou, K. Spiropoulou, V. Bekos, A. Spring, T. Kalatzi, H. Nikolaou, M. Laskou, I. Strouvalis, S. Aloizos, S. Kapogiannis, O. Soldatou, M. Bassetti, C. Adembri, G. Villa, A. Giarratano, S. Maurizio Raineri, Andrea Cortegiani, F. Montalto, M. T. Strano, V. M. Ranieri, C. SANDRONI, G. De Pascale, A. Molin, P. Pelosi, L. Montagnani, R. Urbino, Ilaria Mastromauro, F. G. De Rosa, V. M. Ranieri, T Cardoso, S. Afonso, João Gonçalves-Pereira, J. P. Baptista, Murat Akova, Ahmet Özveren · 发表于：Clinical Infectious Diseases · 年份：2014 · DOI：10.1093/cid/ciu027 · 被引用次数：1110 · 研究领域：Antibiotics Pharmacokinetics and Efficacy、Antibiotic Use and Resistance、Antibiotic Resistance in Bacteria

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. CONCLU...