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      Characteristics and outcomes of culture-negative versus culture-positive severe sepsis

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          Abstract

          Introduction

          Culture-negative sepsis is a common but relatively understudied condition. The aim of this study was to compare the characteristics and outcomes of culture-negative versus culture-positive severe sepsis.

          Methods

          This was a prospective observational cohort study of 1001 patients who were admitted to the medical intensive care unit (ICU) of a university hospital from 2004 to 2009 with severe sepsis. Patients with documented fungal, viral, and parasitic infections were excluded.

          Results

          There were 415 culture-negative patients (41.5%) and 586 culture-positive patients (58.5%). Gram-positive bacteria were isolated in 257 patients, and gram-negative bacteria in 390 patients. Culture-negative patients were more often women and had fewer comorbidities, less tachycardia, higher blood pressure, lower procalcitonin levels, lower Acute Physiology and Chronic Health Evaluation II (median 25.0 (interquartile range 19.0 to 32.0) versus 27.0 (21.0 to 33.0), P = 0.001) and Sequential Organ Failure Assessment scores, less cardiovascular, central nervous system, and coagulation failures, and less need for vasoactive agents than culture-positive patients. The lungs were a more common site of infection, while urinary tract, soft tissue and skin infections, infective endocarditis and primary bacteremia were less common in culture-negative than in culture-positive patients. Culture-negative patients had a shorter duration of hospital stay (12 days (7.0 to 21.0) versus 15.0 (7.0 to27.0), P = 0.02) and lower ICU mortality than culture-positive patients. Hospital mortality was lower in the culture-negative group (35.9%) than in the culture-positive group (44.0%, P = 0.01), the culture-positive subgroup, which received early appropriate antibiotics (41.9%, P = 0.11), and the culture-positive subgroup, which did not (55.5%, P < 0.001). After adjusting for covariates, culture positivity was not independently associated with mortality on multivariable analysis.

          Conclusions

          Significant differences between culture-negative and culture-positive sepsis are identified, with the former group having fewer comorbidities, milder severity of illness, shorter hospitalizations, and lower mortality.

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          Most cited references22

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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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            The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study.

            Define the epidemiology of the four recently classified syndromes describing the biologic response to infection: systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock. Prospective cohort study with a follow-up of 28 days or until discharge if earlier. Three intensive care units and three general wards in a tertiary health care institution. Patients were included if they met at least two of the criteria for SIRS: fever or hypothermia, tachycardia, tachypnea, or abnormal white blood cell count. Development of any stage of the biologic response to infection: sepsis, severe sepsis, septic shock, end-organ dysfunction, and death. During the study period 3708 patients were admitted to the survey units, and 2527 (68%) met the criteria for SIRS. The incidence density rates for SIRS in the surgical, medical, and cardiovascular intensive care units were 857, 804, and 542 episodes per 1000 patient-days, respectively, and 671, 495, and 320 per 1000 patient-days for the medical, cardiothoracic, and general surgery wards, respectively. Among patients with SIRS, 649 (26%) developed sepsis, 467 (18%) developed severe sepsis, and 110 (4%) developed septic shock. The median interval from SIRS to sepsis was inversely correlated with the number of SIRS criteria (two, three, or all four) that the patients met. As the population of patients progressed from SIRS to septic shock, increasing proportions had adult respiratory distress syndrome, disseminated intravascular coagulation, acute renal failure, and shock. Positive blood cultures were found in 17% of patients with sepsis, in 25% with severe sepsis, and in 69% with septic shock. There were also stepwise increases in mortality rates in the hierarchy from SIRS, sepsis, severe sepsis, and septic shock: 7%, 16%, 20%, and 46%, respectively. Of interest, we also observed equal numbers of patients who appeared to have sepsis, severe sepsis, and septic shock but who had negative cultures. They had been prescribed empirical antibiotics for a median of 3 days. The cause of the systemic inflammatory response in these culture-negative populations is unknown, but they had similar morbidity and mortality rates as the respective culture-positive populations. This prospective epidemiologic study of SIRS and related conditions provides, to our knowledge, the first evidence of a clinical progression from SIRS to sepsis to severe sepsis and septic shock.
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              Management of Sepsis

              New England Journal of Medicine, 355(16), 1699-1713
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                Author and article information

                Contributors
                Journal
                Crit Care
                Crit Care
                Critical Care
                BioMed Central
                1364-8535
                1466-609X
                2013
                12 September 2013
                : 17
                : 5
                : R202
                Affiliations
                [1 ]Division of Respiratory and Critical Care Medicine, University Medicine Cluster, National University Hospital, National University Health System Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228
                [2 ]Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228
                [3 ]Faculty of Medicine, Suite H 2743, 300 Prince Philip Drive, Memorial University of Newfoundland, St. John's NL, A1B 3V6, Canada
                [4 ]Department of Medicine, Alexandra Hospital (Jurong Health Services), 378 Alexandra Road, Singapore 159964
                [5 ]RIPAS Hospital, Jalan Putera Al-Muhtadee Billah, Bandar Seri Begawan, BA 1710, Brunei Darussalam
                [6 ]Asian Centre for Liver Diseases and Transplantation, Gleneagles Hospital, Annexe Block, 02-37, 6A Napier Road, Singapore 258500
                Article
                cc12896
                10.1186/cc12896
                4057416
                24028771
                1ad3466f-66c4-44fd-8c58-600584010001
                Copyright © 2013 Phua et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 January 2013
                : 30 April 2013
                : 12 September 2013
                Categories
                Research

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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