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Author(s): Giacomo Grasselli [sup.1] [sup.2], Carolyn S. Calfee [sup.3], Luigi Camporota [sup.4] [sup.5], Daniele Poole [sup.6], Marcelo B. P. Amato [sup.7], Massimo Antonelli [sup.8] [sup.9], Yaseen M. Arabi [sup.10] [sup.11] [...], The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.

Author(s): Ignacio Martin-Loeches [sup.1] [sup.2] [sup.3] [sup.4], Antoni Torres [sup.3] [sup.4], Blin Nagavci [sup.5], Stefano Aliberti [sup.6] [sup.7], Massimo Antonelli [sup.8], Matteo Bassetti [sup.9], Lieuwe D. Bos [sup.10], James D. [...], Purpose Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and whilst European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP. Methods The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations. Results Recommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions. Conclusions In these international guidelines, ERS, ESICM, ESCMID, and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment, and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.

Author(s): Yaseen M. Arabi [sup.1], Bhakti K. Patel [sup.2], Massimo Antonelli [sup.3] [sup.4] Author Affiliations: (1) grid.412149.b, 0000 0004 0608 0662, Intensive Care Department, Ministry of National Guard-Health Affairs, King [...]

Author(s): Gennaro De Pascale [sup.1] [sup.2], Massimo Antonelli [sup.1] [sup.2], Mieke Deschepper [sup.3], Kostoula Arvaniti [sup.4], Koen Blot [sup.5] [sup.6], Ben Creagh Brown [sup.7] [sup.8], Dylan de Lange [sup.9], Jan [...], Purpose To describe data on epidemiology, microbiology, clinical characteristics and outcome of adult patients admitted in the intensive care unit (ICU) with secondary peritonitis, with special emphasis on antimicrobial therapy and source control. Methods Post hoc analysis of a multicenter observational study (Abdominal Sepsis Study, AbSeS) including 2621 adult ICU patients with intra-abdominal infection in 306 ICUs from 42 countries. Time-till-source control intervention was calculated as from time of diagnosis and classified into 'emergency' ( 6 h). Relationships were assessed by logistic regression analysis and reported as odds ratios (OR) and 95% confidence interval (CI). Results The cohort included 1077 cases of microbiologically confirmed secondary peritonitis. Mortality was 29.7%. The rate of appropriate empiric therapy showed no difference between survivors and non-survivors (66.4% vs. 61.3%, p = 0.1). A stepwise increase in mortality was observed with increasing Sequential Organ Failure Assessment (SOFA) scores (19.6% for a value [less than or equal to] 4-55.4% for a value > 12, p < 0.001). The highest odds of death were associated with septic shock (OR 3.08 [1.42-7.00]), late-onset hospital-acquired peritonitis (OR 1.71 [1.16-2.52]) and failed source control evidenced by persistent inflammation at day 7 (OR 5.71 [3.99-8.18]). Compared with 'emergency' source control intervention (< 2 h of diagnosis), 'urgent' source control was the only modifiable covariate associated with lower odds of mortality (OR 0.50 [0.34-0.73]). Conclusion 'Urgent' and successful source control was associated with improved odds of survival. Appropriateness of empirical antimicrobial treatment did not significantly affect survival suggesting that source control is more determinative for outcome.

Author(s): Domenico Luca Grieco [sup.1] [sup.2], Bhakti K. Patel [sup.3], Massimo Antonelli [sup.1] [sup.2] Author Affiliations: (1) grid.414603.4, Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. [...]

Author(s): Massimiliano Greco [sup.1] [sup.2], Thomas De Corte [sup.3] [sup.4], Ari Ercole [sup.5] [sup.6], Massimo Antonelli [sup.7] [sup.8], Elie Azoulay [sup.9] [sup.10], Giuseppe Citerio [sup.11] [sup.12], Andy Conway Morris [sup.13] [...], Purpose To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Methods Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. Results 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%-50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. Conclusions ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality.

ObjectiveTo identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock.DesignA consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations.MethodsEach committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 - supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science.ResultsThe Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction?ConclusionsWhile the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

Author(s): Alexander P. J. Vlaar [sup.1], Joanna C. Dionne [sup.2] [sup.3] [sup.4] [sup.21], Sanne de Bruin [sup.1], Marije Wijnberge [sup.1] [sup.5], S. Jorinde Raasveld [sup.1], Frank E. H. P. van [...], Purpose To develop evidence-based clinical practice recommendations regarding transfusion practices and transfusion in bleeding critically ill adults. Methods A taskforce involving 15 international experts and 2 methodologists used the GRADE approach to guideline development. The taskforce addressed three main topics: transfusion support in massively and non-massively bleeding critically ill patients (transfusion ratios, blood products, and point of care testing) and the use of tranexamic acid. The panel developed and answered structured guideline questions using population, intervention, comparison, and outcomes (PICO) format. Results The taskforce generated 26 clinical practice recommendations (2 strong recommendations, 13 conditional recommendations, 11 no recommendation), and identified 10 PICOs with insufficient evidence to make a recommendation. Conclusions This clinical practice guideline provides evidence-based recommendations for the management of massively and non-massively bleeding critically ill adult patients and identifies areas where further research is needed.

Author(s): Laura Evans [sup.1], Andrew Rhodes [sup.2], Waleed Alhazzani [sup.3], Massimo Antonelli [sup.4], Craig M. Coopersmith [sup.5], Craig French [sup.6], Flávia R. Machado [sup.7], Lauralyn Mcintyre [sup.8], Marlies Ostermann [sup.9], [...]

Author(s): Alberto Zanella [sup.1] [sup.2], Gaetano Florio [sup.1], Massimo Antonelli [sup.3] [sup.4], Giacomo Bellani [sup.5] [sup.6], Angela Berselli [sup.7], Tiziana Bove [sup.8] [sup.9], Luca Cabrini [sup.10], Eleonora Carlesso [sup.1], Gian [...], Purpose To evaluate the daily values and trends over time of relevant clinical, ventilatory and laboratory parameters during the intensive care unit (ICU) stay and their association with outcome in critically ill patients with coronavirus disease 19 (COVID-19). Methods In this retrospective-prospective multicentric study, we enrolled COVID-19 patients admitted to Italian ICUs from February 22 to May 31, 2020. Clinical data were daily recorded. The time course of 18 clinical parameters was evaluated by a polynomial maximum likelihood multilevel linear regression model, while a full joint modeling was fit to study the association with ICU outcome. Results 1260 consecutive critically ill patients with COVID-19 admitted in 24 ICUs were enrolled. 78% were male with a median age of 63 [55-69] years. At ICU admission, the median ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO.sub.2/FiO.sub.2) was 122 [89-175] mmHg. 79% of patients underwent invasive mechanical ventilation. The overall mortality was 34%. Both the daily values and trends of respiratory system compliance, PaO.sub.2/FiO.sub.2, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil-lymphocyte ratio, and platelets were associated with survival, while for lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with survival. The trends of PaO.sub.2/FiO.sub.2, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with survival compared to the daily values. Conclusion Daily values or trends over time of parameters associated with acute organ dysfunction, acid-base derangement, coagulation impairment, or systemic inflammation were associated with patient survival.

Author(s): Alexander P. Vlaar [sup.1] [sup.18], Simon Oczkowski [sup.2] [sup.3] [sup.4], Sanne de Bruin [sup.1], Marije Wijnberge [sup.1] [sup.5], Massimo Antonelli [sup.6] [sup.7], Cecile Aubron [sup.8], Philippe Aries [sup.8], Jacques [...], Objective To develop evidence-based clinical practice recommendations regarding transfusion practices in non-bleeding, critically ill adults. Design A task force involving 13 international experts and three methodologists used the GRADE approach for guideline development. Methods The task force identified four main topics: red blood cell transfusion thresholds, red blood cell transfusion avoidance strategies, platelet transfusion, and plasma transfusion. The panel developed structured guideline questions using population, intervention, comparison, and outcomes (PICO) format. Results The task force generated 16 clinical practice recommendations (3 strong recommendations, 13 conditional recommendations), and identified five PICOs with insufficient evidence to make any recommendation. Conclusions This clinical practice guideline provides evidence-based recommendations and identifies areas where further research is needed regarding transfusion practices and transfusion avoidance in non-bleeding, critically ill adults.

This document summarizes a study conducted by the UNITE-COVID investigators group on co-infection and secondary infection among critically ill COVID-19 patients. The study compared the rates of bacterial co-infection and secondary infections in COVID-19 patients with those in patients with other severe respiratory viral infections. The researchers found that COVID-19 patients had a lower rate of bacterial co-infection on presentation but higher rates of secondary infections. Factors contributing to the high rates of secondary infections included the use of broad-spectrum antimicrobials, immunomodulation with glucocorticoids, and breakdowns in infection control procedures. The study also examined the differences in management and infections between 2020 and 2021, finding changes in adjunctive therapies and reduced use of certain medications. The text discusses the prevalence of secondary infections in COVID-19 patients in 2021, with bacterial pneumonia being the most common. There was also an increase in fungal pneumonia and multi-drug-resistant organisms. Despite changes in treatment practices, the risk of secondary infections increased. The study emphasizes the need for further research on the impact of secondary infections and the use of antimicrobials in COVID-19 patients. The document includes a list of medical professionals and hospitals from various countries involved in the study, as well as the funding source and ethical approval information. Supplementary information in the form of a graph is also provided. [Extracted from the article]

Author(s): Massimo Antonelli [sup.1] [sup.2], Ignacio Martin-Loeches [sup.3] [sup.4], George Dimopoulos [sup.5], Antonio Gasbarrini [sup.6] [sup.2], Maria Sole Vallecoccia [sup.1] [sup.2] Author Affiliations: (1) grid.414603.4, Department of Anesthesiology, Intensive Care [...], Clostridioides difficile (formerly Clostridium difficile) infection (CDI) represents a worrisome condition, often underestimated, with severe clinical presentations, frequently requiring intensive care unit (ICU) admission. The aim of the present expert statement was to give an overview of the management of CDI in critically ill patients, for whom CDI represents a redoubtable problem, in large part related to the use and abuse of antibiotics. The available knowledge about pathophysiology, risk factors, diagnosis and treatment concerning critical care patients affected by CDI has been reviewed, even though most of the existing information come from studies performed outside the ICU and the evidence on several issues in this specific context is scarce. The adoption of potential preventive and therapeutic strategies aimed to stem the phenomenon were discussed, including the faecal microbiota transplantation. This possibility could represent a highly interesting option in critically ill patients, but current evidence is limited and future well designed studies are needed. A special insight on the specific challenges that the ICU physicians may face caring for the critically ill patients with CDI was also proposed.

Author(s): Stijn Blot [sup.1], Massimo Antonelli [sup.2] [sup.3], Kostoula Arvaniti [sup.4], Koen Blot [sup.1], Ben Creagh-Brown [sup.5] [sup.6], Dylan de Lange [sup.7], Jan De Waele [sup.8], Mieke Deschepper [sup.9], Yalim [...], Purpose To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection.

Author(s): Ignacio Martin-Loeches [sup.1] [sup.2], Massimo Antonelli [sup.3], Manuel Cuenca-Estrella [sup.4], George Dimopoulos [sup.5], Sharon Einav [sup.6], Jan J. De Waele [sup.7], Jose Garnacho-Montero [sup.8] [sup.9], Souha S. Kanj [sup.10], [...], Introduction The term invasive candidiasis (IC) refers to both bloodstream and deep-seated invasive infections, such as peritonitis, caused by Candida species. Several guidelines on the management of candidemia and invasive infection due to Candida species have recently been published, but none of them focuses specifically on critically ill patients admitted to intensive care units (ICUs). Material and Methods In the absence of available scientific evidence, the resulting recommendations are based solely on epidemiological and clinical evidence in conjunction with expert opinion. The task force used the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to evaluate the recommendations and assign levels of evidence. The recommendations and their strength were decided by consensus and, if necessary, by vote (modified Delphi process). Descriptive statistics were used to analyze the results of the Delphi process. Statements obtaining > 80% agreement were considered to have achieved consensus. Conclusions The heterogeneity of this patient population necessitated the creation of a mixed working group comprising experts in clinical microbiology, infectious diseases and intensive care medicine, all chosen on the basis of their expertise in the management of IC and/or research methodology. The working group's main goal was to provide clinicians with clear and practical recommendations to optimize microbiological diagnosis and treatment of IC. The Systemic Inflammation and Sepsis and Infection sections of the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) therefore decided to develop a set of recommendations for application in non-immunocompromised critically ill patients.

Author(s): Maurizio Cecconi [sup.1] [sup.2], Glenn Hernandez [sup.3], Martin Dunser [sup.4], Massimo Antonelli [sup.5], Tim Baker [sup.6] [sup.7], Jan Bakker [sup.3] [sup.8] [sup.9] [sup.10] [sup.11], Jacques Duranteau [sup.12] [sup.13], Sharon [...], An international team of experts in the field of fluid resuscitation was invited by the ESICM to form a task force to systematically review the evidence concerning fluid administration using basic monitoring. The work included a particular emphasis on pre-ICU hospital settings and resource-limited settings. The work focused on four main questions: (1) What is the role of clinical assessment to guide fluid resuscitation in shock? (2) What basic monitoring is required to perform and interpret a fluid challenge? (3) What defines a fluid challenge in terms of fluid type, ranges of volume, and rate of administration? (4) What are the safety endpoints during a fluid challenge? The expert panel found insufficient evidence to provide recommendations according to the GRADE system, and was only able to make recommendations for basic interventions, based on the available evidence and expert opinion. The panel identified significant gaps in the scientific evidence on fluid administration outside the ICU (excluding the operating theater). Globally, scientific communities and health care systems should address these critical gaps in evidence through research on how basic fluid administration in resource-rich and resource-limited settings can be improved for the benefit of patients and societies worldwide.

Author(s): D. J. Klein [sup.1], D. Foster [sup.2], P. M. Walker [sup.2], S. M. Bagshaw [sup.3], H. Mekonnen [sup.4], M. Antonelli [sup.5] Author Affiliations: (1) 0000 0001 2157 2938, grid.17063.33, [...], Purpose The EUPHRATES trial examined the impact of polymyxin B hemoperfusion (PMX) on mortality in patients with septic shock and endotoxemia, defined as EAA [greater than or equal to] 0.60. No difference was found in 28-day all-cause mortality. However, the trial showed that in some patients with septic shock the burden of endotoxin activity was extreme (EAA [greater than or equal to] 0.9). In a post hoc analysis, we evaluated the impact of PMX use in patients with septic shock and endotoxin activity measured between 0.6-0.89. Methods Post-hoc analysis of the EUPHRATES trial for the 194 patients with EAA [greater than or equal to] 0.6-0.89 who completed two treatments (PMX or sham). The primary end point was mortality at 28 days adjusted for APACHE II score and baseline mean arterial pressure (MAP). Additional end points included changes in MAP, cumulative vasopressor index (CVI), median EAA reduction, ventilator-free days (VFD), dialysis-free days (DFD) and hospital length of stay. Subpopulations analyzed were site and type of infection and those with norepinephrine dose > 0.1 mcg/kg/min at baseline. Results At 28 days, 23 patients of 88 (26.1%) in the PMX group died versus 39 of 106 (36.8%) in the sham group [risk difference 10.7%, OR 0.52, 95% CI (0.27, 0.99), P = 0.047]. When unadjusted for baseline variables, P = 0.11. The 28-day survival time in the PMX group was longer than for the sham group [HR 0.56 (95% CI 0.33, 0.95) P = 0.03]. PMX treatment compared with sham showed greater change in MAP [median (IQR) 8 mmHg (- 0.5, 19.5) vs. 4 mmHg (- 4.0, 11) P = 0.04] and VFD [median (IQR) 20 days (0.5, 23.5) vs. 6 days (0, 20), P = 0.004]. There were no significant differences in other end points. There was a significant difference in mortality in PMX-treated patients with no bacterial growth on culture [PMX, 6/30 (20%) vs. sham, 13/31 (41.9%), P = 0.005]. The median EAA change in the population was - 12.9% (range: increase 49.2%-reduction 86.3%). The mortality in the above median EAA change group was PMX: 6/38 (15.7%) vs. sham 15/49 (30.6%), P = 0.08. Conclusions These hypothesis-generating results, based on an exploratory post hoc analysis of the EUPHRATES trial, suggest measurable responses in patients with septic shock and an EAA [greater than or equal to] 0.6 to 0.89 on changes in mean arterial pressure, ventilator-free days and mortality. Trial registration Clinicaltrials.gov Identifier: NCT01046669. Funding Spectral Medical Incorporated.

Author(s): Andrew Conway Morris [sup.1] [sup.2], Deepankar Datta [sup.2] [sup.3], Manu Shankar-Hari [sup.4], Jacqueline Stephen [sup.5], Christopher J. Weir [sup.5], Jillian Rennie [sup.2], Jean Antonelli [sup.5], Anthony Bateman [sup.6], Noel [...], Purpose Cellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients. Methods Multi-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (T.sub.regs)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections. Results A total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of T.sub.regs were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00-4.74), 3.44 (1.58-7.47) and 2.41 (1.14-5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9. Conclusions This study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies. Trial registration The study was registered with clinicaltrials.gov (NCT02186522).

Author(s): Jan J. De Waele [sup.1], Murat Akova [sup.2], Massimo Antonelli [sup.3], Rafael Canton [sup.4], Jean Carlet [sup.5], Daniel De Backer [sup.6], George Dimopoulos [sup.7], José Garnacho-Montero [sup.8], Jozef Kesecioglu [...], Antimicrobial resistance (AMR) is a clear and present danger to patients in any intensive care unit (ICU) around the world. Whereas AMR may affect any patient in the hospital, patients in the ICU are particularly at risk of acquiring AMR infections due to the intensity of the treatment, use of invasive devices, increased risk of transmission and exposure to antibiotics. AMR is present in every ICU, although prevalence is geographically different and AMR pathogens encountered are variable. Intensive care and infectious disease specialists from the European Society of Intensive Care Medicine, European Society of Microbiology and Infectious Diseases and World Alliance Against Antimicrobial Resistance, united in the ANTARCTICA (Antimicrobial Resistance in Critical Care) coalition, call for increased awareness and action among health care professionals to reduce AMR development in critically ill patients, to improve treatment of AMR infections and to coordinate scientific research in this high-risk patient population. Close collaboration with other specialties, and combining these and other interventions in antibiotic stewardship programmes should be a priority in every ICU. Considerate antibiotic use and adopting strict infection control practices to halt AMR remains a responsibility shared by all healthcare workers, from physicians to maintenance personnel, from nurses to physiotherapists, from consultants to medical students. Together, we can reduce AMR in our ICUs and continue to treat our patients effectively.

Author(s): Andrew Rhodes [sup.1], Laura E. Evans [sup.2], Waleed Alhazzani [sup.3], Mitchell M. Levy [sup.4], Massimo Antonelli [sup.5], Ricard Ferrer [sup.6], Anand Kumar [sup.7], Jonathan E. Sevransky [sup.8], Charles L. [...], Objective To provide an update to 'Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012'. Design A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. Results The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Conclusions Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Author(s): Claudio Sandroni [sup.1], Sonia D'Arrigo [sup.1], Clifton W. Callaway [sup.2], Alain Cariou [sup.3], Irina Dragancea [sup.4], Fabio Silvio Taccone [sup.5], Massimo Antonelli [sup.1] Author Affiliations: (1) grid.8142.f, 0000000109413192, Department [...], Background The occurrence of brain death in patients with hypoxic-ischaemic brain injury after resuscitation from cardiac arrest creates opportunities for organ donation. However, its prevalence is currently unknown. Methods Systematic review. MEDLINE via PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews were searched for eligible studies (2002-2016). The prevalence of brain death in adult patients resuscitated from cardiac arrest and the rate of organ donation among brain dead patients were summarised using a random effect model with double-arcsine transformation. The quality of evidence (QOE) was evaluated according to the GRADE guidelines. Results 26 studies [16 on conventional cardiopulmonary resuscitation (c-CPR), 10 on extracorporeal CPR (e-CPR)] included a total of 23,388 patients, 1830 of whom developed brain death at a mean time of 3.2 ± 0.4 days after recovery of circulation. The overall prevalence of brain death among patients who died before hospital discharge was 12.6 [10.2-15.2] %. Prevalence was significantly higher in e-CPR vs. c-CPR patients (27.9 [19.7-36.6] vs. 8.3 [6.5-10.4] %; p < 0.0001). The overall rate of organ donation among brain dead patients was 41.8 [20.2-51.0] % (9/26 studies, 1264 patients; range 0-100 %). The QOE was very low for both outcomes. Conclusions In patients with hypoxic-ischaemic brain injury following CPR, more than 10 % of deaths were due to brain death. More than 40 % of brain-dead patients could donate organs. Patients who are unconscious after resuscitation from cardiac arrest, especially when resuscitated using e-CPR, should be carefully screened for signs of brain death.

Author(s): Matteo Bassetti [sup.1], Elda Righi [sup.1], Filippo Ansaldi [sup.2], Maria Merelli [sup.1], Claudio Scarparo [sup.1], Massimo Antonelli [sup.3], Jose Garnacho-Montero [sup.4], Ana Diaz-Martin [sup.4], Inmaculada Palacios-Garcia [sup.4], Roberto Luzzati [...], Purpose Clinical data on patients with intra-abdominal candidiasis (IAC) is still scarce. Methods We collected data from 13 hospitals in Italy, Spain, Brazil, and Greece over a 3-year period (2011-2013) including patients from ICU, medical, and surgical wards. Results A total of 481 patients were included in the study. Of these, 27 % were hospitalized in ICU. Mean age was 63 years and 57 % of patients were male. IAC mainly consisted of secondary peritonitis (41 %) and abdominal abscesses (30 %); 68 (14 %) cases were also candidemic and 331 (69 %) had concomitant bacterial infections. The most commonly isolated Candida species were C. albicans (n = 308 isolates, 64 %) and C. glabrata (n = 76, 16 %). Antifungal treatment included echinocandins (64 %), azoles (32 %), and amphotericin B (4 %). Septic shock was documented in 40.5 % of patients. Overall 30-day hospital mortality was 27 % with 38.9 % mortality in ICU. Multivariate logistic regression showed that age (OR 1.05, 95 % CI 1.03-1.07, P < 0.001), increments in 1-point APACHE II scores (OR 1.05, 95 % CI 1.01-1.08, P = 0.028), secondary peritonitis (OR 1.72, 95 % CI 1.02-2.89, P = 0.019), septic shock (OR 3.29, 95 % CI 1.88-5.86, P < 0.001), and absence of adequate abdominal source control (OR 3.35, 95 % CI 2.01-5.63, P < 0.001) were associated with mortality. In patients with septic shock, absence of source control correlated with mortality rates above 60 % irrespective of administration of an adequate antifungal therapy. Conclusions Low percentages of concomitant candidemia and high mortality rates are documented in IAC. In patients presenting with septic shock, source control is fundamental.