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      Advances in antibiotic therapy in the critically ill

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          Abstract

          Infections occur frequently in critically ill patients and their management can be challenging for various reasons, including delayed diagnosis, difficulties identifying causative microorganisms, and the high prevalence of antibiotic-resistant strains. In this review, we briefly discuss the importance of early infection diagnosis, before considering in more detail some of the key issues related to antibiotic management in these patients, including controversies surrounding use of combination or monotherapy, duration of therapy, and de-escalation. Antibiotic pharmacodynamics and pharmacokinetics, notably volumes of distribution and clearance, can be altered by critical illness and can influence dosing regimens. Dosing decisions in different subgroups of patients, e.g., the obese, are also covered. We also briefly consider ventilator-associated pneumonia and the role of inhaled antibiotics. Finally, we mention antibiotics that are currently being developed and show promise for the future.

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          DALI: defining antibiotic levels in intensive care unit patients: are current β-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 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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            Guidelines for the management of adult lower respiratory tract infections - Full version

            This document is an update of Guidelines published in 2005 and now includes scientific publications through to May 2010. It provides evidence-based recommendations for the most common management questions occurring in routine clinical practice in the management of adult patients with LRTI. Topics include management outside hospital, management inside hospital (including community-acquired pneumonia (CAP), acute exacerbations of COPD (AECOPD), acute exacerbations of bronchiectasis) and prevention. Background sections and graded evidence tables are also included. The target audience for the Guideline is thus all those whose routine practice includes the management of adult LRTI.
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              Trial of short-course antimicrobial therapy for intraabdominal infection.

              The successful treatment of intraabdominal infection requires a combination of anatomical source control and antibiotics. The appropriate duration of antimicrobial therapy remains unclear.
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                Author and article information

                Contributors
                jlvincent@intensive.org
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                17 May 2016
                17 May 2016
                2016
                : 20
                : 133
                Affiliations
                [ ]Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, 1070 Brussels, Belgium
                [ ]Infectious Diseases Division, Santa Maria Misericordia University Hospital, 33100 Udine, Italy
                [ ]Service de Réanimation Polyvalente, CHU de Dupuytren, 87042 Limoges, France
                [ ]Infectious Disease Section, Louisiana State University School of Medicine, 70112 New Orleans, LA USA
                [ ]Réanimation Médicale, Groupe Hospitalier Pitié-Salpêtrière, 75013 Paris, France
                [ ]Department of Pulmonary Medicine, Hospital Clinic of Barcelona, IDIBAPS-Ciberes, 08036 Barcelona, Spain
                [ ]Burns, Trauma and Critical Care Research Centre, The University of Queensland, Royal Brisbane and Women’s Hospital, 4029 Herston, Brisbane, Australia
                [ ]Department of Intensive care, CIBERES, Vall d’Hebron University Hospital, Universitat Autonoma de Barcelona, 08035 Barcelona, Spain
                [ ]Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland
                [ ]Department of Intensive Care, CHIREC Hospital, Université Libre de Bruxelles, 1420 Braine L’Alleud, Belgium
                [ ]Department of Respiratory Medicine, Medizinische Hochschule, 30625 Hannover, Germany
                [ ]Department of Anesthesiology and Intensive Care Medicine, Catholic University of Rome, A. Gemelli University Hospital, Rome, Italy
                Article
                1285
                10.1186/s13054-016-1285-6
                4869332
                27184564
                c8a2e7a9-c612-483f-a249-d5d72baaaf82
                © Vincent et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Funding
                Funded by: National Health and Medical Research Council of Australia
                Award ID: APP1048652, APP1099452
                Award Recipient :
                Categories
                Review
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                © The Author(s) 2016

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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