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      Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study

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          Abstract

          Introduction

          A clinical suspicion of infection is mandatory for diagnosing sepsis in patients with a systemic inflammatory response syndrome. Yet, the accuracy of categorizing critically ill patients presenting to the intensive care unit (ICU) as being infected or not is unknown. We therefore assessed the likelihood of infection in patients who were treated for sepsis upon admission to the ICU, and quantified the association between plausibility of infection and mortality.

          Methods

          We studied a cohort of critically ill patients admitted with clinically suspected sepsis to two tertiary ICUs in the Netherlands between January 2011 and December 2013. The likelihood of infection was categorized as none, possible, probable or definite by post-hoc assessment. We used multivariable competing risks survival analyses to determine the association of the plausibility of infection with mortality.

          Results

          Among 2579 patients treated for sepsis, 13% had a post-hoc infection likelihood of “none”, and an additional 30% of only “possible”. These percentages were largely similar for different suspected sites of infection. In crude analyses, the likelihood of infection was associated with increased length of stay and complications. In multivariable analysis, patients with an unlikely infection had a higher mortality rate compared to patients with a definite infection (subdistribution hazard ratio 1.23; 95% confidence interval 1.03-1.49).

          Conclusions

          This study is the first prospective analysis to show that the clinical diagnosis of sepsis upon ICU admission corresponds poorly with the presence of infection on post-hoc assessment. A higher likelihood of infection does not adversely influence outcome in this population.

          Trial registration

          ClinicalTrials.gov NCT01905033. Registered 11 July 2013.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13054-015-1035-1) contains supplementary material, which is available to authorized users.

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          Most cited references7

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          Septic shock.

          Septic shock, the most severe complication of sepsis, is a deadly disease. In recent years, exciting advances have been made in the understanding of its pathophysiology and treatment. Pathogens, via their microbial-associated molecular patterns, trigger sequential intracellular events in immune cells, epithelium, endothelium, and the neuroendocrine system. Proinflammatory mediators that contribute to eradication of invading microorganisms are produced, and anti-inflammatory mediators control this response. The inflammatory response leads to damage to host tissue, and the anti-inflammatory response causes leucocyte reprogramming and changes in immune status. The time-window for interventions is short, and treatment must promptly control the source of infection and restore haemodynamic homoeostasis. Further research is needed to establish which fluids and vasopressors are best. Some patients with septic shock might benefit from drugs such as corticosteroids or activated protein C. Other therapeutic strategies are under investigation, including those that target late proinflammatory mediators, endothelium, or the neuroendocrine system.
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            The international sepsis forum consensus conference on definitions of infection in the intensive care unit.

            To develop definitions of infection that can be used in clinical trials in patients with sepsis. Infection is a key component of the definition of sepsis, yet there is currently no agreement on the definitions that should be used to identify specific infections in patients with sepsis. Agreeing on a set of valid definitions that can be easily implemented as part of a clinical trial protocol would facilitate patient selection, help classify patients into prospectively defined infection categories, and therefore greatly reduce variability between treatment groups. Experts in infectious diseases, clinical microbiology, and critical care medicine were recruited and allocated specific infection sites. They carried out a systematic literature review and used this, and their own experience, to prepare a draft definition. At a subsequent consensus conference, rapporteurs presented the draft definitions, and these were then refined and improved during discussion. Modifications were circulated electronically and subsequently agreed upon as part of an iterative process until consensus was reached. Consensus definitions of infection were developed for the six most frequent causes of infections in septic patients: pneumonia, bloodstream infections (including infective endocarditis), intravascular catheter-related sepsis, intra-abdominal infections, urosepsis, and surgical wound infections. We have described standardized definitions of the common sites of infection associated with sepsis in critically ill patients. Use of these definitions in clinical trials should help improve the quality of clinical research in this field.
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              Rapid diagnosis of sepsis

              Fast and appropriate therapy is the cornerstone in the therapy of sepsis. However, the discrimination of sepsis from non-infectious causes of inflammation may be difficult. Biomarkers have been suggested to aid physicians in this decision. There is currently no biochemical technique available which alone allows a rapid and reliable discrimination between sepsis and non-infectious inflammation. Procalcitonin (PCT) is currently the most investigated biomarker for this purpose. C-reactive protein and interleukin 6 perform inferior to PCT in most studies and their value in diagnosing sepsis is not defined. All biomarkers including PCT are also released after various non-infectious inflammatory impacts. This shortcoming needs to be taken into account when biomarkers are used to aid the physician in the diagnosis of sepsis. Polymerase chain reaction (PCR) based pathogen detection may improve time to adequate therapy but cannot rule out the presence of infection when negative.
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                Author and article information

                Contributors
                +31 88 756 1116 , p.m.c.kleinklouwenberg@umcutrecht.nl
                o.l.cremer@umcutrecht.nl
                l.a.vanvught@amc.uva.nl
                d.s.y.ong@umcutrecht.nl
                j.f.frencken@umcutrecht.nl
                marcus.j.schultz@gmail.com
                m.j.m.bonten@umcutrecht.nl
                t.vanderpoll@amc.uva.nl
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                7 September 2015
                7 September 2015
                2015
                : 19
                : 1
                : 319
                Affiliations
                [ ]Department of Intensive Care Medicine, University Medical Center Utrecht, Room F06.149, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
                [ ]Department of Medical Microbiology, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
                [ ]Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
                [ ]Center for Experimental and Molecular Medicine and Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
                [ ]Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
                Article
                1035
                10.1186/s13054-015-1035-1
                4562354
                26346055
                90afaef5-7bea-4d21-829e-29a4b84b41aa
                © Klein Klouwenberg et al. 2015

                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
                : 30 May 2015
                : 15 August 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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