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

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 o...

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Bibliographic Details
Published in:Clinical infectious diseases 2014-04, Vol.58 (8), p.1072-1083
Main Authors: Roberts, J. A., De Waele, J. J., Dimopoulos, G., Koulenti, D., Martin, C., Montravers, P., Rhodes, A., Starr, T., Wallis, S. C., Lipman, J., Margarit Ribas, A., Spapen, H., Dugernier, T., Jorens, P., Dapper, I., De Backer, D., Ruano, L., Afonso, E., Alvarez-Lerma, F., Fernandez, F., Bardolet, N., Garro, P., Colon, D., Castillo, C., Lopez, M. J., Ots, E., Catalan, M., Prieto, I., Gonzalo, G., Galvan, B., Meyer, E., Del Nogal, F., Vidaur, L., Sebastian, R., Garde, P. M., Esperatti, M., Mahjoub, Y., Payen, J. F., Albanese, J., Malledant, Y., Pottecher, J., Lefrant, J.-Y., Joannes-Boyau, O., Orban, C., Ostermann, M., McKenzie, C., Smith, J., Gordon, A., Brett, S., Stotz, M., Templeton, M., Moran, C., Xristodoulou, A., Theodorou, V., Kouliatsis, G., Sertaridou, E., Anthopoulos, G., Choutas, G., Balla, M., Papanikolaou, M., Gavala, A., Fildisis, G., Kyriakopoulou, M., Petrochilou, K., Kompoti, M., Clouva-Molyvdas, F.-M., Gkiokas, G., Psychogiou, V., Akoumianaki, E., Lilitsis, E., Nakos, G., Kalogirou, M., Zafeiridis, T., Chaintoutis, C., Arvaniti, K., Matamis, D., Giannakou, M., Antoniadou, E., Koukoubani, T., Paraforou, T., Spiropoulou, K., Spring, A., Kalatzi, T., Nikolaou, H., Strouvalis, I., Aloizos, S., Kapogiannis, S., Adembri, C., Villa, G., Giarratano, A., Maurizio Raineri, S., Cortegiani, A., Montalto, F., De Pascale, G., Molin, A., Pelosi, P., Urbino, R., Mastromauro, I., De Rosa, F. G., Cardoso, T.
Format: Article
Language:English
Subjects:
Antibiotics
Clinical outcomes
Drug dosages
Human health and pathology
Immunology
Infectious diseases
Intensive care
Life Sciences
Microbiology and Parasitology
Patients
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Summary: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 ...) and 100% (100% f ...) 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 ... 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 ... and 100% f ... 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. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:1058-4838
1537-6591
DOI:10.1093/cid/ciu027