The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) present clinical criteria for the classification of patients with sepsis. We investigated incidence and long-term outcomes of patients diagnosed with these classifications, which are currently unknown.

The Sepsis-3 Criteria emphasized the value of a change of 2 or more points in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, introduced quick SOFA (qSOFA), and removed the systemic inflammatory response syndrome (SIRS) criteria from the sepsis definition.

Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.

Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition.

The Third International Consensus Definitions Task Force defined sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection." The performance of clinical criteria for this sepsis definition is unknown.

Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains.

Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain.

In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary.

Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established.

The Surviving Sepsis Campaign recommends targeting a mean arterial pressure of at least 65 mm Hg during initial resuscitation of patients with septic shock. However, whether this blood-pressure target is more or less effective than a higher target is unknown.

Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis.

In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were "to provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive injurious process that falls under the generalized term 'sepsis' and includes sepsis-associated organ dysfunction as well." The general definitions introduced as a result of that conference have been widely used in practice and have served as the foundation for inclusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes.

To define the terms "sepsis" and "organ failure" in a precise manner.

Joseph A. Hippensteel

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 8, Page 981-983, October 15, 2018.

Acute kidney injury is a frequent complication in patients hospitalized in the intensive care unit (ICU) for septic shock and is associated with high mortality. Acute kidney injury associated with sepsis is characterized by a distinct pathophysiology, and patients with acute kidney injury and……

Lai, Chih-Cheng; Wang, Ya-Hui; Wang, Cheng-Yi; Wang, Hao-Chien; Yu, Chong-Jen; Chen, Likwang; on the behalf of Taiwan Clinical Trial Consortium for Respiratory Diseases (TCORE)

Objectives: This study aimed to compare the effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk and outcomes of sepsis in patients with chronic obstructive pulmonary disease. Design: A retrospective study. Setting: Taiwan’s National Health Insurance Research Database. Patients: All patients with chronic obstructive pulmonary disease who received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for more than 90 days between 2000 and 2005 were recruited for this study. Pairwise matching (1:1) of the angiotensin-converting enzyme inhibitor and angiotensin receptor blocker groups resulted in two similar subgroups with 5,959 patients in each. Interventions: None. Measurements and Main Results: The primary outcome was sepsis, and the secondary outcome was death. The occurrence rate of sepsis was 3.67 per 100 person-years for the patients receiving angiotensin-converting enzyme inhibitors and 2.87 per 100 person-years for those receiving angiotensin receptor blockers. In addition, the patients receiving angiotensin-converting enzyme inhibitors had a higher risk of septic shock (adjusted hazard ratio, 1.45; 95% CI, 1.26–1.67) and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.22–1.40) than those receiving angiotensin receptor blockers. No matter whether the patients had prior severe exacerbation before the index date, those receiving angiotensin-converting enzyme inhibitors had a higher risk of sepsis, septic shock, and mortality than those receiving angiotensin receptor blockers (all p < 0.001). Conclusions: Angiotensin receptor blockers were associated with lower rates of sepsis and mortality than angiotensin-converting enzyme inhibitors in the patients with chronic obstructive pulmonary disease. The similar findings were also noted in subgroup analysis. Members of Taiwan Clinical Trial Consortium for Respiratory Diseases (TCORE) are listed in the acknowledgments. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by grants from National Science Council (104-2314-B-002-185-MY2, 101-2325-B-002-064, 102-2325-B-002-087, 103-2325-B-002-027, 104-2325-B-002-035, 105-2325-B-002-030, 104-2314-B-567-002, 105-2314-B-567-001), and from National Health Research Institutes (intramural funding). Dr. Cheng-Yi Wang disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: cywang@mospital.com Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Meihong Deng, Yiting Tang, Wenbo Li, Xiangyu Wang, Rui Zhang, Xianying Zhang, Xin Zhao, Jian Liu, Cheng Tang, Zhonghua Liu, Yongzhuo Huang, Huige Peng, Lehui Xiao, Daolin Tang, Melanie J. Scott, Qingde Wang, Jing Liu, Xianzhong Xiao, Simon Watkins, Jianhua Li, Huan Yang, Haichao Wang, Fangping Chen, Kevin J. Tracey, Timothy R. Billiar, Ben Lu

Caspase-11, a cytosolic LPS receptor, mediates endotoxic shock. Deng and colleagues demonstrate that hepatocyte-released HMGB1 mediates caspase-11-dependent pyroptosis and lethality in sepsis by delivering extracellular LPS into the cytosol of macrophages and endothelial cells, where LPS activates caspase-11.

Christopher W. Seymour

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 7, Page 832-833, October 1, 2018.

Russell R. Miller

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 7, Page 903-913, October 1, 2018.

Viriya Hantrakun, Ranjani Somayaji, Prapit Teparrukkul, Chaiyaporn Boonsri, Kristina Rudd, Nicholas P. J. Day, T. Eoin West, Direk Limmathurotsakul

by Viriya Hantrakun, Ranjani Somayaji, Prapit Teparrukkul, Chaiyaporn Boonsri, Kristina Rudd, Nicholas P. J. Day, T. Eoin West, Direk Limmathurotsakul Infection and sepsis are leading causes of death worldwide but the epidemiology and outcomes are not well understood in resource-limited settings. We conducted a four-year prospective observational study from March 2013 to February 2017 to examine the clinical epidemiology and outcomes of adults admitted with community-acquired infection in a resource-limited tertiary-care hospital in Ubon Ratchathani province, Northeast Thailand. Hospitalized patients with infection and accompanying systemic manifestations of infection within 24 hours of admission were enrolled. Subjects were classified as having sepsis if they had a modified sequential organ failure assessment (SOFA) score ≥2 at enrollment. This study was registered with ClinicalTrials.gov, number NCT02217592. A total of 4,989 patients were analyzed. Of the cohort, 2,659 (53%) were male and the median age was 57 years (range 18–101). Of these, 1,173 (24%) patients presented primarily to the study hospital, 3,524 (71%) were transferred from 25 district hospitals or 8 smaller hospitals in the province, and 292 (6%) were transferred from one of 30 hospitals in other provinces. Three thousand seven hundred and sixteen (74%) patients were classified as having sepsis. Patients with sepsis had an older age distribution and a greater prevalence of comorbidities compared to patients without sepsis. Twenty eight-day mortality was 21% (765/3,716) in sepsis and 4% (54/1,273) in non-sepsis patients (p

Paul E Marik

Glucocorticoids have been used as adjunctive therapy in patients with sepsis and septic shock for more than four decades. The rationale for the use of glucocorticoids is that this class of drugs downregulates the proinflammatory response and limits the anti-inflammatory response while preserving innate immunity. Between 1976 and 2017, 22 randomised placebo-controlled trials have been published evaluating the benefit of glucocorticoids in patients with community-acquired pneumonia, sepsis, and septic shock.

Ranzani, Otavio T.; Shankar-Hari, Manu; Harrison, David A.; Rabello, Lígia S.; Salluh, Jorge I. F.; Rowan, Kathryn M.; Soares, Marcio

Objectives: To test whether differences in both general and sepsis-specific patient characteristics explain the observed differences in sepsis mortality between countries, using two national critical care (ICU) databases. Design: Cohort study. Setting: We analyzed 62 and 164 ICUs in Brazil and England, respectively. Patients: Twenty-two–thousand four-hundred twenty-six adult ICU admissions from January 2013 to December 2013. Interventions: None. Measurements and Main Results: After harmonizing relevant variables, we merged the first ICU episode of adult medical admissions from Brazil (ORganizational CHaractEeriSTics in cRitical cAre study) and England (Intensive Care National Audit & Research Centre Case Mix Programme). Sepsis-3 definition was used, and the primary outcome was hospital mortality. We used multilevel logistic regression models to evaluate the impact of country (Brazil vs England) on mortality, after adjustment for general (age, sex, comorbidities, functional status, admission source, time to admission) and sepsis-specific (site of infection, organ dysfunction type and number) patient characteristics. Of medical ICU admissions, 13.2% (4,505/34,150) in Brazil and 30.7% (17,921/58,316) in England met the sepsis definition. The Brazil cohort was older, had greater prevalence of severe comorbidities and dependency compared with England. Respiratory was the most common infection site in both countries. The most common organ dysfunction was cardiovascular in Brazil (41.2%) and respiratory in England (85.8%). Crude hospital mortality was similar (Brazil 41.4% vs England 39.3%; odds ratio, 1.12 [0.98–1.30]). After adjusting for general patient characteristics, there was an important change in the point-estimate of the odds ratio (0.88 [0.75–1.02]). However, after adjusting for sepsis-specific patient characteristics, the direction of effect reversed again with Brazil having higher risk-adjusted mortality (odds ratio, 1.22 [1.05–1.43]). Conclusions: Patients with sepsis admitted to ICUs in Brazil and England have important differences in general and sepsis-specific characteristics, from source of admission to organ dysfunctions. We show that comparing crude mortality from sepsis patients admitted to the ICU between countries, as currently performed, is not reliable and that the adjustment for both general and sepsis-specific patient characteristics is essential for valid international comparisons of mortality amongst sepsis patients admitted to critical care units. Drs. Rowan and Soares are senior authors. † In memoriam. The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service, the National Institute for Health Research or the Department of Health. Drs. Ranzani and Shankar-Hari are equal contributors. Dr. Ranzani did data analyses. Drs. Ranzani and Shankar-Hari wrote the first draft of the article. Drs. Harrison, Rabello, Salluh, Rowan, and Soares led data collection. Dr. Rabello died during the peer-review process of this article. All authors unanimously agreed on her fundamental contribution for this study. All authors conceptualized and designed the study, interpreted data, and critically revised the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The original ORganizational CHaractEeriSTics in cRitical cAre study was supported by the National Council for Scientific and Technological Development (Grant number 304240/2014-1), Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro and by departmental funds from the D’Or Institute for Research and Education. The Case Mix Programme is a subscription-based, national quality assessment program. The current study was funded internally by Intensive Care National Audit & Research Centre. The funding sources had no role in the design, conduct or analyses of the study. Dr. Shankar-Hari is supported by the National Institute for Health Research Clinician Scientist Award (NIHR-CS-2016-16-011). Dr. Soares disclosed that he is founder and equity shareholder at Epimed Solutions. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: otavioranzani@usp.br Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Introduction Staphylococcus aureus frequently causes infections in outpatient and hospital settings and can present as a highly variable entity. Typical manifestations are endocarditis, osteoarticular infections or infection of implanted prostheses, intravascular devices or foreign bodies. A thorough diagnostic evaluation with early focus identification is mandatory to improve patient outcome. Case report We report a case of a 68-year old patient with a history of double allogeneic stem cell transplant for acute myeloid leukemia who developed a S. aureus bacteremia with dissemination, severe sepsis and lethal outcome due to nasal handkerchief packing after nose bleeding. Conclusion A thorough medical examination with further diagnostic work-up is most important in S. aureus blood stream infection to identify and eradicate the portal(s) of entry, to rule out endocarditis, to search for spinal abscesses, osteomyelitis or spondylodiscitis. Adherence to management guides for clinicians must be of major importance to achieve optimal quality of clinical care, and thus improve patient outcome.

The original version of this article unfortunately contained mistakes.

Kubra Aykac , Eda Karadag Oncel , Sevgen Tanir Basaranoglu , Alpaslan Alp , Ali Bulent Cengiz , Mehmet Ceyhan , Ates Kara

Abstract Background Knowledge of infections leading sepsis is needed to develop comprehensive infection prevention and sepsis early recognition and treatment strategies.The aim of this study was to investigate the etiology of sepsis and evaluate the proportion of respiratory viral pathogens in infants under two years of age with possible sepsis. Methods The prospective study was performed in two years. Multiplex RT‐PCR was performed to detect viral pathogens. All patients who were included in this study had sepsis symptoms as defined by the Surviving Sepsis Campaign. Results We compared 90 patients with sepsis into three groups as patients (n=33) had only viral positivity in nasopharyngeal swab and patients (17) had proven bacterial infection with or without viral infection and patients (40) without pathogen detection. Human rhinovirus (16.7%) and influenza (7.8%) were the most commonly seen viruses. Cough was more common in viral infection group than other groups (p=0.02) and median thrombocyte count was lower in bacterial infection group than the others (p=0.01). Patients had bacterial sepsis had the longest duration of hospitalization than the other groups (p=0.04). In winter and spring patients with sepsis mostly had viral infection however in summer and autumn patients were mostly that we could not prove an infection agents (p=0.02). Conclusions Our results suggest that respiratory tract viruses may play an important role in patients with sepsis and they should be kept in mind especially in winter and spring seasons. With an overall viral respiratory viruses as a single pathogen detection rate of 36.6% in sepsis etiology. This article is protected by copyright. All rights reserved.

Carter, G. P., Ussher, J. E., Goncalves Da Silva, A., Baines, S. L., Heffernan, H., Riley, T. V., Broadbent, R., van der Linden, A., Lee, J., Monk, I. R., Stinear, T. P., Howden, B. P., Williamson, D. A.

Coagulase-negative staphylococci (CoNS) such as Staphylococcus capitis, are major causes of bloodstream infections in neonatal intensive care units (NICUs). Recently a distinct clone of S. capitis (designated S. capitis NRCS-A) has emerged as an important pathogen in NICUs internationally. Here, 122 S. capitis isolates from New Zealand (NZ) underwent whole genome sequencing (WGS), and these data were supplemented with publicly available S. capitis sequence reads. Phylogenetic and comparative genomic analyses were performed, as were phenotypic assessments of antimicrobial resistance, biofilm formation and plasmid segregational stability on representative isolates. A distinct lineage of S. capitis was identified in NZ, associated with neonates and the NICU environment. Isolates from this lineage produced increased levels of biofilm, displayed higher levels of tolerance to chlorhexidine, and were multidrug-resistant. Although similar to globally circulating NICU-associated S. capitis at a core genome level, NZ NICU S. capitis isolates carried a novel, stably maintained multidrug-resistant plasmid that was not present in non-NICU isolates. Neonatal blood culture isolates were indistinguishable to environmental S. capitis isolates found on fomites such as stethoscopes and neonatal incubators, but were generally distinct from those isolates carried by NICU staff. This work implicates the NICU environment as a potential reservoir for neonatal sepsis caused by S. capitis, and highlights the capacity of genomics-based tracking and surveillance to inform future hospital infection control practices aimed at containing the spread of this important neonatal pathogen.

Kievlan, Daniel R.; Zhang, Li A.; Chang, Chung-Chou H.; Angus, Derek C.; Seymour, Christopher W.

Objectives: Among patients with suspected infection, a single measurement of the quick Sepsis-related Organ Failure Assessment has good predictive validity for sepsis, yet the increase in validity from repeated measurements is unknown. We sought to determine the incremental predictive validity for sepsis of repeated quick Sepsis-related Organ Failure Assessment measurements over 48 hours compared with the initial measurement. Design: Retrospective cohort study. Setting: Twelve hospitals in southwestern Pennsylvania in 2012. Patients: All adult medical and surgical encounters in the emergency department, hospital ward, postanesthesia care unit, and ICU. Interventions: None. Measurements and Main Results: Among 1.3 million adult encounters, we identified those with a first episode of suspected infection. Using the maximum quick Sepsis-related Organ Failure Assessment score in each 6-hour epoch from onset of suspected infection until 48 hours later, we characterized repeated quick Sepsis-related Organ Failure Assessment with: 1) summary measures (e.g., mean over 48 hr), 2) crude trajectory groups, and 3) group-based trajectory modeling. We measured the predictive validity of repeated quick Sepsis-related Organ Failure Assessment using incremental changes in the area under the receiver operating characteristic curve for in-hospital mortality beyond that of baseline risk (age, sex, race/ethnicity, and comorbidity). Of 37,591 encounters with suspected infection, 1,769 (4.7%) died before discharge. Both the mean quick Sepsis-related Organ Failure Assessment at 48 hours (area under the receiver operating characteristic, 0.86 [95% CI, 0.85–0.86]) and crude trajectory groups (area under the receiver operating characteristic, 0.83 [95% CI, 0.83–0.83]) improved predictive validity compared with initial quick Sepsis-related Organ Failure Assessment (area under the receiver operating characteristic, 0.79 [95% CI, 0.78–0.80]) (p < 0.001 for both). Group-based trajectory modeling found five trajectories (quick Sepsis-related Organ Failure Assessment always low, increasing, decreasing, moderate, and always high) with greater predictive validity than the initial measurement (area under the receiver operating characteristic, 0.85 [95% CI, 0.84–0.85]; p < 0.001). Conclusions: Repeated measurements of quick Sepsis-related Organ Failure Assessment improve predictive validity for sepsis using in-hospital mortality compared with a single measurement of quick Sepsis-related Organ Failure Assessment at the time a clinician suspects infection. This work was performed at the University of Pittsburgh School of Medicine. Drs. Kievlan, Angus, and Seymour contributed to study concept and design; Drs. Kievlan and Seymour contributed to acquisition of data; Drs. Kievlan, Zhang, Chang, Angus, and Seymour contributed to analysis and interpretation of data; Dr. Kievlan contributed to first drafting of the article; Drs. Kievlan, Zhang, Chang, Angus, and Seymour contributed to critical revision of the article for important intellectual content; Drs. Kievlan, Chang, and Seymour contributed to statistical analysis; Drs. Kievlan and Seymour contributed to sdministrative, technical, and material support; Dr. Seymour contributed to study supervision: Drs. Kievlan and Seymour contributed to data access and responsibility and they had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals/.lww.com/ccmjournal). Supported, in part, by the National Institutes of Health, T32HL007820 (to Dr. Kievlan) and R35GM119519 (to Drs. Chang, Angus, and Seymour). Dr. Kievlan’s institution received funding from National Heart, Lung, and Blood Institute, and he disclosed that Drs. Chang, Angus, and Seymour received support from the National Institute of General Medical Services. Drs. Kievlan, Zhang, Chang, and Seymour received support for article research from the National Institutes of Health (NIH). Drs. Zhang’s and Seymour’s institutions received funding from the NIH. Dr. Seymour received funding from Beckman Coulter. For information regarding this article, E-mail: daniel.kievlan@gmail.com Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Kuehn B.

Clinicians are being urged to monitor patients after platelet transfusion for signs of bacterial infection after 2 separate US outbreaks linked to these blood products led to serious illnesses and deaths.

Abstract Purpose Pre-clinical animal studies precede the majority of clinical trials. While the clinical sepsis definitions and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May, 2017. The conference goal was to identify limitations of pre-clinical sepsis models and to propose a set of guidelines, defined as the “Minimum Quality Threshold in Pre-Clinical Sepsis Studies” (MQTiPSS), to enhance translational value of these models. Methods 31 experts from 13 countries participated and were divided into 6 thematic Working Groups (WG): (1) Study Design, (2) Humane modeling, (3) Infection types, (4) Organ failure/dysfunction, (5) Fluid resuscitation and (6) Antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002–2013). Results Overall, the participants reached consensus on 29 points; 20 at “recommendation” (R) and 9 at “consideration” (C) strength. This Executive Summary provides a synopsis of the MQTiPSS consensus (Tables 1–3). Conclusions We believe that these recommendations and considerations will serve to bring a level of standardization to pre-clinical models of sepsis and ultimately improve translation of pre-clinical findings. These guideline points are proposed as “best practices” that should be implemented for animal sepsis models. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection and Intensive Care Medicine Experimental.

Kidson, Kristen M.; Henderson, William R.; Hutcheon, Jennifer A.

Objectives: Case fatality in pregnancy-associated severe sepsis or septic shock appears reduced compared with nonpregnant women with severe sepsis or septic shock. It remains unclear if this difference is due to pregnancy or better baseline health status, among others. Our study compared adverse outcomes of pregnancy-associated severe sepsis or septic shock with nonpregnant women with severe sepsis or septic shock while controlling for age and chronic comorbidities. Design: Retrospective cohort study. Setting: Nationwide Inpatient Sample, a stratified sample of 20% acute care hospital admissions in the United States. Each entry includes patient and hospital characteristics as well as International Classification of Diseases, 9th revision, Clinical Modification, diagnoses and procedures. Subjects: Women of childbearing age (15–44 yr) with severe sepsis or septic shock–related hospitalizations during 1998–2012 identified using International Classification of Diseases, 9th revision, Clinical Modification, codes. Outcomes: Case fatality, hospital length of stay, length of stay until death, number of organ failures, rates of mechanical ventilation, and hemodialysis were compared in women according to pregnancy status, controlling for age, and chronic comorbidities. Measurements and Main Results: We identified 5,968 pregnancy-associated severe sepsis or septic shock and 85,240 nonpregnant women with severe sepsis or septic shock hospitalizations. Crude case fatality of pregnancy-associated severe sepsis or septic shock (9.6%) was lower than nonpregnant women with severe sepsis or septic shock (16.8%). The rate ratio for case fatality adjusted for socioeconomic status and race was 0.57 (95% CI, 0.52–0.62) while sequential adjustments for age and chronic comorbidities did not eliminate the association (rate ratio, 0.62 [95% CI, 0.57–0.68]) and 0.63 [95% CI, 0.57–0.68], respectively). Pregnancy-associated severe sepsis or septic shock was associated with shorter hospital length of stay (–0.83 d [95% CI, –1.32 to –0.34 d]), longer length of stay until death (2.61 d; [95% CI, 1.28–3.94 d]), and fewer organ failures (rate ratio, 0.95 [95% CI, 0.94–0.97]). Conclusions: Case fatality and adverse outcomes are reduced in women with pregnancy-associated severe sepsis or septic shock compared with nonpregnant women with severe sepsis or septic shock, and this is not explained by differences in age or chronic comorbidities alone. A less severe presentation of sepsis or protective effect of pregnancy may account for the difference observed with pregnancy-associated severe sepsis or septic shock. This work was performed at University of British Columbia. Ethics: This study was exempt from review by the University of British Columbia/British Columbia Children’s and Women’s Hospital Research Ethic Board as it used deidentified, publicly available data. Dr. Kidson was involved in the study concept, design, analysis, and interpretation of data, drafting the article, and critical review of the article. Dr. Henderson was responsible for study design, interpretation of data, and critical review of the article. Dr. Hutcheon was responsible for study design, data acquisition, analysis and interpretation of data, and critical review of the article. All authors approved the final version submitted for publication. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: kmsokalski@alumni.ubc.ca Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Irving, Sharon Y.; Daly, Bridget; Verger, Judy; Typpo, Katri V.; Brown, Ann-Marie; Hanlon, Alexandra; Weiss, Scott L.; Fitzgerald, Julie C.; Nadkarni, Vinay M.; Thomas, Neal J.; Srinivasan, Vijay; for the Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Netw

Objectives: The impact of nutrition status on outcomes in pediatric severe sepsis is unclear. We studied the association of nutrition status (expressed as body mass index z score) with outcomes in pediatric severe sepsis. Design: Secondary analysis of the Sepsis Prevalence, Outcomes, and Therapies study. Patient characteristics, ICU interventions, and outcomes were compared across nutrition status categories (expressed as age- and sex-adjusted body mass index z scores using World Health Organization standards). Multivariable regression models were developed to determine adjusted differences in all-cause ICU mortality and ICU length of stay by nutrition status. Setting: One-hundred twenty-eight PICUs across 26 countries. Patients: Children less than 18 years with severe sepsis enrolled in the Sepsis Prevalence, Outcomes, and Therapies study (n = 567). Interventions: None. Measurements and Main Results: Nutrition status data were available for 417 patients. Severe undernutrition was seen in Europe (25%), Asia (20%), South Africa (17%), and South America (10%), with severe overnutrition seen in Australia/New Zealand (17%) and North America (14%). Severe undernutrition was independently associated with all-cause ICU mortality (adjusted odds ratio, 3.0; 95% CI, 1.2–7.7; p = 0.02), whereas severe overnutrition in survivors was independently associated with longer ICU length of stay (1.6 d; p = 0.01). Conclusions: There is considerable variation in nutrition status for children with severe sepsis treated across this selected network of PICUs from different geographic regions. Severe undernutrition was independently associated with higher all-cause ICU mortality in children with severe sepsis. Severe overnutrition was independently associated with greater ICU length of stay in childhood survivors of severe sepsis. Members of the Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study Investigators are listed in Appendix 1. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by the Endowed Chair, Department of Anesthesia and Critical Care, University of Pennsylvania Perelman School of Medicine, and the Center for Pediatric Clinical Effectiveness at the Children’s Hospital of Philadelphia. Dr. Weiss is also supported by National Institute of General Medical Sciences K23GM110496. Financial support for data collection in all U.K. centers was provided by the U.K. National Institute of Health (NIHR) Clinical Research Network and in Southampton by the Southampton NIHR Wellcome Trust Clinical Research Facility. None of the funders participated in the design and conduct of study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the article. Dr. Daly received funding from the Biostatistics Consulting Unit at the University of Pennsylvania School of Nursing. Dr. Typpo’s institution received funding from the National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases, and Baxter. Dr. Brown received funding from Akron Children’s Hospital Foundation for a different research project, but none related to this project. Dr. Hanlon’s institution received funding from the Children’s Hospital of Philadelphia (CHOP). Dr. Weiss’s institution received funding from Center for Pediatric Clinical Effectiveness at CHOP and National Institute of General Medical Sciences K23GM110496; he received funding from ThemoFisher Scientific (honoraria for lectures unrelated to current topic), Medscape via an unrestricted grant from Roche, and Bristol-Myers Squibb Company (Member of Advisory Panel); and he received support for article research from the NIH. Dr. Fitzgerald’s institution received funding from CHOP Center for Pediatric Clinical Effectiveness. Dr. Thomas received funding from Therabron, CareFusion, and Gene Fluidics. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: srinivasan@email.chop.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Background The emergence and spread of antibiotic resistant micro-organisms is a global concern, which is largely attributable to inaccurate prescribing of antibiotics to patients presenting with non-bacterial infections. The use of ‘omics’ technologies for discovery of novel infection related biomarkers combined with novel treatment algorithms offers possibilities for rapidly distinguishing between bacterial and viral infections. This distinction can be particularly important for patients suffering from lower respiratory tract infections (LRTI) and/or sepsis as they represent a significant burden to healthcare systems. Here we present the study details of the TAILORED-Treatment study, an observational, prospective, multi-centre study aiming to generate a multi-parametric model, combining host and pathogen data, for distinguishing between bacterial and viral aetiologies in children and adults with LRTI and/or sepsis. Methods A total number of 1200 paediatric and adult patients aged 1 month and older with LRTI and/or sepsis or a non-infectious disease are recruited from Emergency Departments and hospital wards of seven Dutch and Israeli medical centres. A panel of three experienced physicians adjudicate a reference standard diagnosis for all patients (i.e., bacterial or viral infection) using all available clinical and laboratory information, including a 28-day follow-up assessment. Nasal swabs and blood samples are collected for multi-omics investigations including host RNA and protein biomarkers, nasal microbiota profiling, host genomic profiling and bacterial proteomics. Simplified data is entered into a custom-built database in order to develop a multi-parametric model and diagnostic tools for differentiating between bacterial and viral infections. The predictions from the model will be compared with the consensus diagnosis in order to determine its accuracy. Discussion The TAILORED-Treatment study will provide new insights into the interplay between the host and micro-organisms. New host- or pathogen-related biomarkers will be used to generate a multi-parametric model for distinguishing between bacterial and viral infections. This model will be helpful to better guide antimicrobial therapy for patients with LRTI and sepsis. This study has the potential to improve patient care, reduce unnecessary antibiotic prescribing and will contribute positively to institutional, national and international healthcare economics. Trial Registration NCT02025699. Registration Date: January, 1, 2014.