Alexis Tabah
email: a.tabah@uq.edu.au

Niccolò Buetti

Quentin Staiquly

Stéphane Ruckly

Murat Akova

Abdullah Tarik Aslan

Marc Leone

Andrew Conway Morris

Matteo Bassetti

Kostoula Arvaniti

Alexis Tabah1

Niccolo Buetti5

Quentin Staiquly7

Stephane Ruckly6

Murat Akova8

Abdullah Tarik Aslan9

Marc Leone10

Andrew Conway

Matteo Bassetti14

Kostoula Arvaniti15

Jeffrey Lipman4

Ricard Ferrer18

Haibo Qiu19

Jose Artur Paiva20

Pedro Povoa23

Liesbet De Bus26

Jan De Waele27

Farid Zand29

Mohan Gurjar30

Adel Alsisi31

Khalid Abidi33

Hendrik Bracht34

Yoshiro Hayashi35

Kyeongman Jeon36

Muhammed Elhadi37

Francois Barbier38

Jean-Francois Timsit39

Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study

Keywords: bloodstream infection, bacteremia, hospital-acquired, antibiotic resistance

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Introduction

Hospital-acquired bloodstream infections (HA-BSI) are the healthcare-associated infection causing the highest burden in disability-adjusted life years [START_REF] Cassini | Burden of six healthcare-associated infections on European population health: estimating incidence-based disability-adjusted life years through a population prevalence-based modelling study[END_REF]. They are relatively frequent in intensive care unit (ICU) patients and are associated with 36-42% mortality [START_REF] Tabah | Characteristics and determinants of outcome of hospitalacquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study[END_REF][START_REF] Vincent | Prevalence and outcomes of infection among patients in intensive care units in 2017[END_REF][START_REF] Adrie | Attributable mortality of ICU-acquired bloodstream infections: impact of the source, causative micro-organism, resistance profile and antimicrobial therapy[END_REF][START_REF] Prowle | Acquired bloodstream infection in the intensive care unit: incidence and attributable mortality[END_REF]. In 2012, the EUROBACT-1 international cohort study highlighted the prevalence of multidrug resistant organisms and its association with higher risk of death in ICU patients with HABSI.

In recent years, worrisome increases in antimicrobial resistance have been highlighted by agencies and scientific societies worldwide [START_REF] De Waele | Antimicrobial resistance and antibiotic stewardship programs in the ICU: insistence and persistence in the fight against resistance. A position statement from ESICM/ESCMID/WAAAR round table on multidrug resistance[END_REF][START_REF] Bezabih | Comparison of the global prevalence and trend of human intestinal carriage of ESBL-producing Escherichia coli between healthcare and community settings: a systematic review and meta-analysis[END_REF][START_REF]Global antimicrobial resistance and use surveillance system (GLASS) report[END_REF]. Indeed, antimicrobial resistance is associated with delays to adequate antimicrobial therapy, increased mortality, resource utilization and costs [START_REF] Tabah | Characteristics and determinants of outcome of hospitalacquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study[END_REF][START_REF] Murray | Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis[END_REF][START_REF] Cosgrove | The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs[END_REF]. It leads to considerable increases in the use of broad-spectrum antimicrobials which in turn exacerbates the problem by selecting antimicrobial resistant micro-organisms. Given the frequency of sepsis, septic shock, and the high mortality in ICU patients with HA-BSI, large international studies are essential to identify potentially modifiable factors of poor prognosis. These data may inform patient care, the development of guidelines, and the design of clinical trials.

The EUROBACT-2 study was designed to update the epidemiology and main factors associated with day-28 mortality in ICU patients with HA-BSI by prospectively collecting granular center, patient, pathogen, treatment, and outcome data from ICUs worldwide.

Methods

Study design

EUROBACT-2 was a prospective international cohort study, registered with ClinicalTrials.org (NCT03937245) and reported in accordance with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines [START_REF] Von Elm | The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies[END_REF]. The study was conducted across the first year of the pandemic caused by coronavirus disease 2019 (COVID-19). We reported the differences in the epidemiology of HABSI in patients with COVID-19 separately [START_REF] Buetti | Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study[END_REF]. Initial ethical approval as a low-risk research project with waiver of individual consent was granted by the Human Research Ethics Committee of the Royal Brisbane & Women's Hospital, Queensland, Australia (LNR/2019/ QRBW/48376). Each study site then obtained ethical and governance approvals according to national and/or local regulations.

Setting

Endorsement, financial, and logistical support were obtained from the European Society of Intensive Care Medicine (ESICM) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP). The operational committee (AT, NB, FB, SR, QS, CD, JFT) oversaw study operations under the responsibility of the primary investigator (AT). Logistics were provided by the OUTCOMEREA non-profit research group (Paris, France). National coordinators recruited participating ICUs, applied for ethical and regulatory approvals, and facilitated communication within their country.

Participants

We included adult (≥ 18 years of age) patients with a HABSI treated in the ICU. HA-BSI was defined as a positive blood culture sampled more than 48 h after hospital admission. Treatment in the ICU was defined as the blood culture having been either sampled in the ICU or the patient having been transferred to the ICU for the treatment of the HA-BSI. Detailed definitions are available in the electronic supplemental material (ESM).

For usually considered as common contaminants (list provided in the ESM), at least 2 blood cultures with the same antimicrobial susceptibility profile, or strong clinical grounds that it was not a contaminant (e.g., intravascular catheters or other infected material proven as a source for the HA-BSI) were mandatory. All possible contaminants were carefully reviewed for eligibility by the operational committee in collaboration with the local investigators and excluded if the above criteria were not met.

Data collection

Centers prospectively recruited patients between the 1 st of June 2019 and the 30th of January 2021, with a minimum of 10 consecutive patients or for a 3-month period, which on request could be extended. Hospital and ICU characteristics were recorded. Patient data were retrieved from the hospital charts without additional tests or interventions. Demographic data, the main diagnosis at ICU admission, and comorbidities were collected. Geographical regions and income categories were defined using the United Nations M49 standard [START_REF]Standard country and area codes for statistical use[END_REF]. Severity of illness was assessed at ICU admission by the Simplified Acute Physiology Score II (SAPS II) [START_REF] Gall | A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study[END_REF], and at HA-BSI diagnosis by the Sequential Organ Failure Assessment (SOFA) score [START_REF] Vincent | The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine[END_REF]. Given all included patients had an infection, sepsis was defined at HA-BSI diagnosis according to Sepsis III criteria by a SOFA score ≥ 2, and septic shock as sepsis plus v sopressor use plus lactate > 2 mmol/L [START_REF] Singer | The third international consensus definitions for sepsis and septic shock (sepsis-3)[END_REF]. We focused on each patient's first episode of HA-BSI, collected pathogen with antibiogram, date and time of blood culture sampling and followed patients for 28 days, until hospital discharge, or death. Blood culture sampling represented the time zero of the study from which all timings were calculated (e.g., time to adequate antimicrobial therapy). Sources of HA-BSI were recorded in order of clinical likelihood according to the treating clinician. Primary HA-BSI was defined as no clear portal of entry or source of infection. Antimicrobials were collected from 2 days prior to HA-BSI to ICU discharge or day-28 follow-up. Carbapenem resistance for Enterobacterales was defined as resistance to at least one carbapenem [START_REF]Carbapenem-resistant enterobacterales (CRE): CRE technical information[END_REF]. Difficult-to-treat resistance (DTR) was defined as resistance to all first line antimicrobials [START_REF] Kadri | Difficult-to-treat resistance in gram-negative bacteremia at 173 US hospitals: retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents[END_REF], and pan-drugresistance (PDR) as resistance to all tested antimicrobials. To avoid over-reporting DTR and PDR for pathogens with incompletely reported antibiograms, the assessment required availability of antimicrobial susceptibility testing for at least one fluoroquinolone, one cephalosporin, one carbapenem, plus polymyxins for PDR. DTR and PDR were assessed for Enterobacterales, Pseudomonas spp., and Acinetobacter spp. Adequate antimicrobial therapy was defined as receiving at least 1 antimicrobial with invitro activity for the pathogen at the considered timepoint, with adequacy of antimicrobial selection, dosing and administration manually reviewed for all infections and sources of HA-BSI. Time to adequate antimicrobial therapy was defined as the time between sampling of the first positive blood culture and receipt of at least one adequate antibiotic for each pathogen. Source control was reported according to the source and intervention, with adequacy assessed by the investigator.

Statistical analysis

As detailed in the ESM, and to ensure consistency, database lock was made on the 12/08/2021 after answering of all queries by the investigators, crosschecking with electronic controls, and careful reading of all the case-report forms by the operational committee. Linearity to the logit for continuous variables was checked with generalized additive models. Non-linear variables were discretised into categorical variables based on quartiles. Continuous variables were expressed as medians (interquartile range [IQR]) and categorical variables as absolute frequencies and percentage. Differences were tested by the Wilcoxon rank-sum test for continuous variables and Fisher's exact test for categorical variables.

To identify factors associated with day-28 death, we built a three-tiered hierarchical logistic mixed model and a subdistribution hazard frailty model that considered ICU discharge as a competing risk, as suggested by Fine and Gray [START_REF] Fine | A proportional hazards model for the subdistribution of a competing risk[END_REF]. Both are presented in the ESM as exploratory analyses, alongside sensitivity analysis excluding COVID-19 patients and investigating the role of carbapenem resistance in place of DTR. All analyses were two sided with p values less than 0.05 deemed statistically significant. Statistical analysis was done using SAS 9.4 statistical software (SAS Institute Inc., Cary, NC, USA) and R project version 4.04.

Results

Study population

We enrolled 2600 patients from 333 ICUs in 52 countries or territories (ESM eFigures 1-2, Table 1 and eTables 2-3). Most ICUs were in public (83.8%), teaching (82.6%) hospitals, with a mixed medical-surgical (79.5%) and general case mix (91.7%). Median [IQR] ICU size was 14 [10; 21] ventilator-equivalent beds with wide variability in infrastructure and factors related to antimicrobial stewardship.

ICUs recruited a median [IQR] of 6 [START_REF] Vincent | Prevalence and outcomes of infection among patients in intensive care units in 2017[END_REF][START_REF] Cosgrove | The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs[END_REF] [5; 11] at HA-BSI diagnosis, with 4% of the patients not meeting the criteria for sepsis, while 64.2% and 31.7% met the criteria for sepsis and septic shock, respectively (Table 3). Sources of infection were predominantly respiratory (pneumonia) (26.7%) and intravascular catheters (26.4%), followed by the abdomen (15.1%). While primary HA-BSI were common (16.3%), one third of the patients (32.8%) had more than one possible source of HA-BSI.

Pathogens

Most (88.8%) blood cultures were mono-microbial, with 10% containing two, and 1.2% more than two pathogens, resulting in a total of 2927 bacterial and fungal isolates.

Antimicrobial therapy and source control

Adequate antimicrobial therapy was received by 51.5% within 24 h of blood culture sampling. As shown in Fig. 1, time to adequate antimicrobial therapy increased with antimicrobial resistance (p < 0.0001). The 3 antimicrobials most frequently administered in the 24 h following HA-BSI diagnosis included meropenem 463/2600 (17.8%), piperacillin/ tazobactam 380/2600 (14.6%), and vancomycin 266/2600 (10.2%). They were deemed adequate in 275/463 (59.4%), 244/380 (64.2%), and 132/266 (49.6%) prescriptions, respectively. Source control was deemed to be required for 52.5% of the patients and was effectively achieved in 81.8% of these, after a median of 24.5 [IQR 1;72] hours.

Mortality

By day-28, 966 (37.1%) patients had died, 91% in the ICU and 9% after ICU discharge. Death was preceded by a decision to withhold or withdraw life-sustaining treatment for 268 (27.7%). At that time point, 38.7% of the survivors were still in the ICU, 35.7% had been discharged from the ICU, and 25.6% had been discharged from the hospital, which represents 16.1% of the total cohort. Multiple factors were associated with day-28 mortality in the univariable analysis (Tables 1,2,3). At center level these included medical ICUs, lower availability of clinical pharmacists and of therapeutic drug monitoring (TDM) for aminoglycosides or vancomycin. Mortality was higher in patients with co-morbidities, medical and COVID-19 admissions, and those with higher severity of illness, including requirements for organ supportive therapy. Higher mortality was found in early ICU-acquired HA-BSI, respiratory sources, DTR Gram-negative bacteria or fungus, and patients who did not receive adequate antimicrobials or for whom source control was required but not achieved. There was no statistically significant association between time to adequate antimicrobial therapy and day-28 mortality.

Factors associated with death in the multivariable hierarchical logistic model and with an increased subdistribution hazard ratio (sHR) of death at day-28 in a competitive risk model are shown in eTable 5. In summary, factors that were statistically significant in both models included infrequent clinical pharmacist consultation, older age, severity of illness at HA-BSI, DTR Gram negative bacteria, and not achieving source control for patients who required an intervention. Conversely, achieving source control was protective in both analyses.

Discussion

EUROBACT-2 provides an update on the epidemiology and prognostic factors of HA-BSI in the ICU by including 2600 patients from 333 ICUs in 5 continents. We report substantial day-28 mortality, especially in HA-BSI caused by DTR pathogens, patients with septic shock, and those who never received adequate antibiotics or source control. There was a broad range of sources of infection and pathogens. Gram-negative bacteria were frequently carbapenem resistant or DTR. Antibiotic resistance was associated with longer delays to adequate antibiotics. Center data showed important variability of service availability including for the variables related to antimicrobial stewardship.

To our knowledge, the EUROBACT-2 study represents the largest international study of HA-BSI s in ICU patients. Few large international studies have investigated this population, which limits possibilities for direct comparisons with our data. We conducted the EUROBACT-1 study in 2010, with a similar methodology but a smaller group of ICUs [START_REF] Tabah | Characteristics and determinants of outcome of hospitalacquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study[END_REF]. The EPIC III point prevalence study investigated the prevalence and outcomes of ICU patients with infections in 2017 and was not limited to hospital-acquired or bloodstream infections [START_REF] Vincent | Prevalence and outcomes of infection among patients in intensive care units in 2017[END_REF]. As shown in Table 4, the two EUROBACT studies showed a predominance of Gram-negative bacteria. In comparison, bloodstream pathogens from the EPIC III cohort showed a higher proportion of Gram-positive bacteria, with more Staphylococcus spp. but less Enterococcus spp. The European Centre for Disease Prevention and Control (ECDC) epidemiological report of hospital-acquired infections in the ICU, computed from 2017 data, showed a predominance of Gram-positive pathogens in HA-BSI. There were 23.6% coagulase-negative staphylococci and 14.9% Enterococcus spp., followed by 12.4% Klebsiella spp. [START_REF]Healthcare-associated infections acquired in intensive care units[END_REF]. While some of these differences may be explained by the inclusion of community-acquired infections in EPIC III, the lower proportion coagulase-negative staphylococci in our study is probably secondary to the careful review of each case and discussion with the investigators, leading to the exclusion of all potential blood culture contaminants that did not meet the inclusion criteria. Between EUROBACT-1 and 2, the proportion of MRSA has decreased by 10%, and the proportion of vancomycin resistant Enterococcus (VRE) has remained stable. Interestingly, there has been an increase in the proportion of non-albicans Candida spp., which have now become dominant. Carbapenem resistance has substantially increased, especially for Enterobacter spp. and Acinetobacter spp., leading to a substantial proportion of DTR in Gram-negative pathogens, and up to 1.6% PDR for Pseudomonas spp. and 2.3% for Acinetobacter spp. In keeping with previous reports, and as shown in eTables 5 and 7, carbapenem resistance and DTR in Gram-negative bacteremia were associated with mortality, highlighting the importance of strategies aimed at preventing and treating infections caused by multidrug resistant pathogens [START_REF] Tabah | Characteristics and determinants of outcome of hospitalacquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study[END_REF][START_REF] Kadri | Difficult-to-treat resistance in gram-negative bacteremia at 173 US hospitals: retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents[END_REF][START_REF] Bonnet | Influence of bacterial resistance on mortality in intensive care units: a registry study from 2000 to 2013 (IICU Study)[END_REF][START_REF] Huh | Impact of difficult-totreat resistance in gram-negative bacteremia on mortality: retrospective analysis of nationwide surveillance data[END_REF]. A detailed description of the of the pathogens causing HA-BSI in the COVID-19 population is reported separately [START_REF] Buetti | Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study[END_REF].

Ten years after the first EUROBACT-2 study, we observed comparable delays to adequate antimicrobial therapy as around half of the patients received such within 24 h of blood culture sampling. Antimicrobial resistance was associated with delays. In the setting of widespread resistance to broad-spectrum antibiotics, molecular rapid diagnostic testing may be a key for earlier adequate antimicrobial treatment [START_REF] Giacobbe | Rapid microbiological tests for bloodstream infections due to multidrug resistant Gram-negative bacteria: therapeutic implications[END_REF][START_REF] Banerjee | Randomized trial of rapid multiplex polymerase chain reaction-based blood culture identification and susceptibility testing[END_REF]. That delays to adequate antimicrobial therapy were not associated with day-28 mortality may be subsequent to multiple confounders and should be interpreted with caution. Indeed, the relationship between time to antimicrobial therapy and mortality in observational research is complicated [START_REF] Weinberger | A critical analysis of the literature on time-toantibiotics in suspected sepsis[END_REF]. On the one hand, the clinical impression of severity may be a driver for earlier administration of broader spectrum antimicrobials to patients with an increased risk of death. Moreover, a non-negligible proportion of patients with sepsis may inexorably die, regardless of the antibiotic treatment. Others may have died before antibiogram results could be acted upon, eliminating an opportunity for antimicrobial adequacy. On the other hand, patients identified at lower risk may have been treated later, when positive microbiology was reported [START_REF] Hranjec | Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensivecare-unit-acquired infection: a quasi-experimental, before and after observational cohort study[END_REF]. Another source of immortal-time bias may be present as some patients with HA-BSI may have never been diagnosed or included in the study. Some may have died before they could be transferred to the ICU, underestimating mortality, while others may have rapidly improved, before ICU admission, overestimating mortality of HA-BSI. These findings do not challenge the recommendation for early adequate antimicrobial therapy for patients with sepsis or septic shock [START_REF] Evans | Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021[END_REF]. Indeed, while we need to avoid antibiotic overuse and its associated harms [START_REF] Curran | Estimating daily antibiotic harms: an umbrella review with individual study meta-analysis[END_REF], early adequate antimicrobial therapy is one of the most important interventions for HA-BSI [START_REF] Evans | Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021[END_REF].

How can these observations improve clinical practice? The exploratory analysis suggests a protective effect of source control and a possible detrimental effect of infrequent clinical pharmacist consultation. These highlight the importance of a multidisciplinary approach for managing critically ill patients with HA-BSI, and by extension, severe infections. Hospitals require integrated pathways, protocols, and educational programs targeting recognition, diagnosis, and treatment of sepsis, including prediction of antimicrobial resistance, antimicrobial prescription, and source control [START_REF] Evans | Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021[END_REF][START_REF] Goodman | A clinical decision tree to predict whether a bacteremic patient is infected with an extendedspectrum beta-lactamase-producing organism[END_REF][START_REF] Dellit | Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship[END_REF]. The optimisation of antimicrobial therapy in critically ill patients involves a multifaceted approach. Pharmacodynamic/ pharmacokinetic optimisation and adequate exposure at the source of infection requires optimal dosing and delivery, considering potential interactions, modified volume of distribution, and decreased or augmented renal clearance [START_REF] Heffernan | A personalised approach to antibiotic pharmacokinetics and pharmacodynamics in critically ill patients[END_REF]. Integrated antimicrobial stewardship programs may facilitate clinically relevant advice and recommendations for therapeutic drug monitoring, and a discussion on source control [START_REF] De Waele | Antimicrobial resistance and antibiotic stewardship programs in the ICU: insistence and persistence in the fight against resistance. A position statement from ESICM/ESCMID/WAAAR round table on multidrug resistance[END_REF][START_REF] Evans | Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021[END_REF][START_REF] Tabah | Use of antimicrobials for bloodstream infections in the intensive care unit, a clinically oriented review[END_REF].

There are important limitations to this study. Firstly, ICUs were predominantly from the Europe and Central Asia and the East Asia and Pacific regions, and from high-income and upper-middle-income countries, thus limiting the generalizability of our results. Second, we started data collection before and continued during the first year of the COVID-19 pandemic. This likely influenced the patient population, microorganism distribution, antimicrobial resistance and mortality [START_REF] Grasselli | Hospital-acquired infections in critically ill patients with COVID-19[END_REF][START_REF] Buetti | COVID-19 increased the risk of ICU-acquired bloodstream infections: a case-cohort study from the multicentric OUTCOMEREA network[END_REF]. Some ICUs were unable to start or complete the study, leading to multiple exclusions. However, we report similar patient severity, pathogen distribution, and mortality to the EUROBACT-1 study, validating the current report. Thirdly, pathogen identification and antimicrobial susceptibility testing relied on each laboratory, with possible differences in interpretation leading to inconsistencies. The patients at risk of late onset BSI had to stay in the ICU for more than 7 days to be exposed to this risk, leading to potential selection bias. The method used for the multivariable analysis led to poor calibration, which is now presented in the ESM. Moreover, data collection was performed by individual investigators in 330 ICUs, without on-site monitoring. We improved the risk of inconsistencies with online checks through the electronic case report file, and by closely monitoring data quality and coherence for each case-report.

Interpretation

HA-BSI in ICU patients was mainly caused by Gramnegative bacteria, with widespread carbapenem resistance and DTR. Antibiotic resistance was associated with longer delays to adequate antimicrobial therapy. HA-BSI was associated with 37.1% mortality, and by day-28 only 16.1% of the patients had been discharged alive from the hospital. Multifaceted programs to decrease multidrug resistance as well as prevent, recognize, and manage HABSI, with a focus on antimicrobial adequacy and source control are suggested to improve patient management and outcomes.

  patients. Most patients were males (63.7%), median [IQR] age was 64 [52;73] years, and 74.8% had at least one comorbidity (Table 2 and eTable 2). Most common ICU admission diagnoses were non-COVID-19-related respiratory failure (21.2%), sepsis or septic shock (20.4%), and COVID-19 (12.9%). Median [IQR] time from hospital admission to HABSI was 13 [8;25] days. Most HA-BSI (78.5%) were ICU acquired (median [IQR] time from ICU admission to diagnosis, 10 [5; 18] days). The median [IQR] SOFA score was 8

  Pathogens were most commonly Gram-negative (1726/2927; 59%), with a predominance of Klebsiella spp. (482/1726; 27.9%), Acinetobacter spp. (350/1726; 20.3%), Escherichia coli (272/1726; 15.8%) and Pseudomonas spp. (247/1726; 14.3%) (Table 4 and ESM eFigure 3). Carbapenem resistance was encountered in 37.8% (182/482) Klebsiella spp., 84.6% (296/350) Acinetobacter spp., 7.4% (20/272) Escherichia coli and 33.2% (82/247) Pseudomonas spp. When analysing Enterobacterales, Pseudomonas spp. and Acinetobacter spp., DTR was present in 23.5% (351/1492) and PDR in 1.5% (23/1492).

	Gram-positive
	pathogens (910/2972; 31.1%) were mainly Enterococcus spp. (314/910, 34.5%) and
	coagulase-negative staphylococci (273/910, 30%). Of the 27.6% (251/910) Staphylococcus
	aureus, 37.1% (93/251) were methicillin-resistant Staphylococcus aureus (MRSA). There
	were 2.1% (61/2927) strict anaerobe bacteria, and 7.9% (230/2927) fungi of which 39.6%
	(91/230) were Candida albicans, 57.8% (133/230) non-albicans Candida spp., and 6 (2.6%)
	other fungi.

Acknowledgements

The EUROBACT-2 study was endorsed by the European Society of Intensive Care Medicine (ESICM), the infection section of the ESCIM and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP), with scientific input of the OUTCOMEREA network. The members of the Eurobact 2 Study Group are: Alexis Tabah, Hamish Pollock, Ben Margetts, Meredith Young, Neeraj Bhadange, Steven Tyler, Anne Ledtischke, Mackenzie Finnis, Anne Ledtischke, Mackenzie Finnis, Jyotsna Dwivedi, Manoj Saxena, Vishwanath Biradar, Natalie Soar, Vineet Sarode, David Brewster, Adrian Regli, Elizabeth Weeda, Samiul Ahmed, Cheryl

MA reports honoraria paid to his university for educational activities by Pfizer, Sanofi, MSD and Astra Zeneca, ATA has nothing to disclose, ML reported consulting and lecture fees from Amomed Pharma, Aspen, LFB and Gilead, ACM has received payment for speaking on behalf of Boston Scientific and sits on the Scientific Advisory Board of Cambridge Infection Diagnostics, a start-up seeking to develop novel diagnostics for infectious diseases, MB received advisory board, speaker activities from Angelini, Bayer, Biomerieux, Cidara, Gilead, Menarini, MSD, Pfizer, Roche, MSD, Pfizer, Astra-Zeneca, Gilead, Jansen, for Gilead, Technophage and Sanofi, lectures fees from MSD, Gilead and Pfizer, and research grant from Abionic, LDB has nothing to disclose, JdW has consulted for Pfizer, MSD (honoraria paid to institution), lecture fees, conference invitation from MSD and lecture fees from BioMérieux, J-FT reported advisory boards participation for Merck, Gilead, Beckton-Dickinson, Pfizer, Shinogi, Medimune, Paratek, research grants from Merck, Pfizer, Thermofischer.

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Shahnaz Hasan, Muhamad Fadhil Hadi Jamaluddin, Lee See Pheng, Sheshendrasurian Visvalingam, Mun Thing Liew, Siong Ling Danny Wong, Kean Khang Fong, Hamizah Bt Abdul Rahman, Zuraini Md Noor, Lee Kok Tong, Abd. Hamid Azman, Mohd Zulfakar Mazlan, Saedah Ali, Kyeongman Jeon, Sang-Min Lee, Sunghoon Park, Seung Yong Park, Sung Yoon Lim, Qing Yuan Goh, Shin Yi Ng, Sui An Lie, Andrea Lay Hoon Kwa, Ken Junyang Goh, Andrew Yunkai Li, Caroline Yu Ming Ong, Jia Yan Lim, Jessica Lishan Quah, Kangqi Ng, Louis Xiang Long Ng, Yu Chang Yeh, Nai-Kuan Chou, Cong-Tat Cia, Ting-Yu Hu, Li-Kuo Kuo, Shih-Chi Ku, Phunsup Wongsurakiat, Yutthana Apichatbutr, Supattra Chiewroongroj, Rashid Nadeem, Ashraf El Houfi, Adel Alsisi, Amr Elhadidy, Mina Barsoum, Nermin Osman, Tarek Mostafa, Mohamed Elbahnasawy, Ahmed Saber, Amer Aldhalia, Omar Elmandouh, Ahmed Elsayed, Merihan A. Elbadawy, Ahmed K. Awad, Hanan M. Hemead, Farid Zand, Maryam Ouhadian, Seyed Hamid Borsi, Zahra Mehraban, Davood Kashipazha, Fatemeh Ahmadi, Mohsen Savaie, Farhad Soltani, Mahboobeh Rashidi, Reza Baghbanian, Fatemeh Javaherforoosh, Fereshteh Amiri, Arash Kiani, Mohammad Amin Zargar, Ata Mahmoodpoor, Fatemeh Aalinezhad, Gholamreza Dabiri, Golnar Sabetian, Hakimeh Sarshad, Mansoor Masjedi, Ramin Tajvidi, Seyed Mohammad Nasirodin Tabatabaei, Abdullah Khudhur Ahmed, Pierre Singer, Ilya Kagan, Merav Rigler, Daniel Belman, Phillip Levin, Belal Harara, Adei Diab, Fayez Abilama, Rebecca Ibrahim, Aya Fares, Ahmad Buimsaedah, Marwa Gamra, Ahmed Aqeelah, Almajdoub Ali Mohammed Ali, Ahmed Gaber Sadik Homaidan, Bushray Almiqlash, Hala Bilkhayr, Ahmad Bouhuwaish, Ahmed Sa Taher, Eman Abdulwahed, Fathi A. Abousnina, Aisha Khaled Hdada, Rania Jobran, Hayat Ben Hasan, Rabab Shaban Ben Hasan, Issam Serghini, Rachid Seddiki, Brahim Boukatta, Nabil Kanjaa, Doumiri Mouhssine, Maazouzi Ahmed Wajdi, Tarek Dendane, Amine Ali Zeggwagh, Brahim Housni, Oujidi Younes, Abdelhamid Hachimi, A. Ghannam, Z. Belkhadir, Sarah Amro, Mustafa Abu Jayyab, Ali Ait Hssain, Abdurahaman Elbuzidi, Edin Karic, Marcus Lance, Shaikh Nissar, Hend Sallam, Omar Elrabi, Ghaleb A. Almekhlafi, Maher Awad, Ahmed Aljabbary, Mohammad Karam Chaaban, Natalia Abu-Sayf, Mohammad Al-Jadaan, Lubna Bakr, Mounir Bouaziz, Olfa Turki, Walid Sellami, Pablo Centeno, Lic Natalia Morvillo, Jose Oscar Acevedo, Patricia Mabel Lopez, Ruben Fernandez, Matias Segura, Dra Marta Aparicio, Microbiologa Irene Alonzo, Yanina Nuccetelli, Pablo Montefiore, Luis Felipe Reyes, Luis Felipe Reyes, Silvio A. Namendys-Silva, Juan P. Romero-Gonzalez, Mariana Hermosillo, Roberto Alejandro Castillo, Jesus Nicolas Pantoja Leal, Candy Garcia Aguilar, Mara Ocotlan Gonzalez Herrera, Missael Vladimir Espinoza Villafuerte, Manuel Lomeli-Teran, Jose G. Dominguez-Cherit, Adrian Davalos-Alvarez, Silvio A. Namendys-Silva, Luis Sanchez-Hurtado, Brigitte Tejeda-Huezo, Orlando R. Perez-Nieto, Ernesto Deloya Tomas, Liesbet De Bus, Jan De Waele, Isabelle Hollevoet, Wouter Denys, Marc Bourgeois, Sofie F. M. Vanderhaeghen, Jean-Baptiste Mesland, Pierre Henin, Lionel Haentjens, Patrick Biston, Cinderella Noel, Nathalie Layos, Benoit Misset, Nicolas De Schryver, Nicolas Serck, Xavier Wittebole, Elisabeth De Waele, Godelive Opdenacker, Pedja Kovacevic, Biljana Zlojutro, Aida Custovic, Ina Filipovic-Grcic, Radovan Radonic, Ana Vujaklija Brajkovic, Jasminka Persec, Sanja Sakan, Mario Nikolic, Hrvoje Lasic, Marc Leone, Charlotte Arbelot, Jean-Francois Timsit, Juliette Patrier, N. Zappela, P. Montravers, Thierry Dulac, Jeremy Castanera, Johann Auchabie, Anthony Le Meur, A. Marchalot, M. Beuzelin, Alexandre Massri, Charlotte Guesdon, Etienne Escudier, Philippe Mateu, Jeremy Rosman, Olivier Leroy, Serge Alfandari, Alexandru Nica, Bertrand Souweine, Elisabeth Coupez, Thibault Duburcq, Eric Kipnis, Perrine Bortolotti, Mathieu Le Souhaitier, Jean-Paul Mira, Pierre Garcon, Matthieu Duprey, Martial Thyrault, Remi Paulet, Francois Philippart, Marc Tran, Cedric Bruel, Emmanuel Weiss, Sylvie Janny, Arnaud Foucrier, Pierre-Francois Perrigault, Flora Djanikian, Francois Barbier, Marc Gainnier, Jeremy Bourenne, Guillaume Louis, Roland Smonig, Laurent Argaud, Thomas Baudry, Armand Mekonted Dessap, Keyvan Razazi, Pierre Kalfon, Gaetan Badre, Romaric Larcher, Jean-Yves Lefrant, Claire Roger, Benjamine Sarton, Stein Silva, Sophie Demeret, Loic Le Guennec, Shidasp Siami, Christelle Aparicio, Guillaume Voiriot, Muriel Fartoukh, Claire Dahyot-Fizelier, Nadia Imzi, Kada Klouche, Hendrik Bracht, Sandra Hoheisen, Frank Bloos, Daniel Thomas-Rueddel, Sirak Petros, Bastian Pasieka, Simon Dubler, Karsten Schmidt, Antje Gottschalk, Carola Wempe, Philippe Lepper, Carlos Metz, Dmitriy Viderman, Yerlan Ymbetzhanov, Miras Mugazov, Yelena Bazhykayeva, Zhannur Kaligozhin, Baurzhan Babashev, Yevgeniy Merenkov, Talgat Temirov, Kostoula Arvaniti, Dimitrios Smyrniotis, Vasiliki Psallida, Georgios Fildisis, Vasiliki Soulountsi, Evangelos Kaimakamis, Cristina Iasonidou, Sofia Papoti, Foteini Renta, Maria Vasileiou, Vasiliki Romanou, Vasiliki Koutsoukou, Mariana Kristina Matei, Leora Moldovan, Ilias Karaiskos, Harry Paskalis, Kyriaki Marmanidou, M. Papanikolaou, C. Kampolis, Marina Oikonomou, Evangelos Kogkopoulos, Charikleia Nikolaou, Anastasios Sakkalis, Marinos Chatzis, Maria Georgopoulou, Anna Efthymiou, Vasiliki Chantziara, Aikaterini Sakagianni, Zoi Athanasa, Eirini Papageorgiou, Fadi Ali, Georges Dimopoulos, Mariota Panagiota Almiroudi, Polychronis Malliotakis, Diamantina Marouli, Vasiliki Theodorou, Ioannis Retselas, Vasilios Kouroulas, Georgios Papathanakos, Giorgia Montrucchio, Gabriele Sales, Gennaro De Pascale, Luca Maria Montini, Simone Carelli, Joel Vargas, Valentina Di Gravio, Daniele Roberto Giacobbe, Angelo Gratarola, Elisa Porcile, Michele Mirabella, Ivan Daroui, Giovanni Lodi, Francesco Zuccaro, Maria Grazia Schlevenin, Paolo Pelosi, Denise Battaglini, Andrea Cortegiani, Mariachiara Ippolito, Davide Bellina, Andrea Di Guardo, Lorella Pelagalli, Marco Covotta, Monica Rocco, Silvia Fiorelli, Antonella Cotoia, Anna Chiara Rizzo, Adam Mikstacki, Barbara Tamowicz, Irmina Kaptur Komorowska, Anna Szczesniak, Jozef Bojko, Anna Kotkowska, Paulina Walczak-Wieteska, Dominika Wasowska, Tomasz Nowakowski, Hanna Broda, Mariusz Peichota, Iwona Pietraszek-Grzywaczewska, Ignacio Martin-Loeches, Alessandra Bisanti, Nuno Cartoze, Tiago Pereira, Nadia Guimaraes, Madalena Alves, Ana Josefina Pinheiro Marques, Ana Rios Pinto, Andriy Krystopchuk, Ana Teresa, Antonio Manuel Pereira de Figueiredo, Isabel Botelho, Tiago Duarte, Vasco Costa, Rui Pedro Cunha, Elena Molinos, Tito da Costa, Sara Ledo, Joana Queiro, Dulce Pascoalinho, Cristina Nunes, Jose Pedro Moura, Enio Pereira, Antonio Carvalho Mendes, Liana Valeanu, Serban Bubenek-Turconi, Ioana Marina Grintescu, Cristian Cobilinschi, Daniela Carmen Filipescu, Cornelia Elena Predoi, Dana Tomescu, Mihai Popescu, Alexandra Marcu, Ioana Grigoras, Olguta Lungu, Alexey Gritsan, Anastasia Anderzhanova, Yulia Meleshkina, Marat Magomedov, Nadezhda Zubareva, Maksim Tribulev, Denis Gaigolnik, Aleksandr Eremenko, Natala Vistovskaya, Maria Chukina, Vladislav Belskiy, Mikhail Furman, Ricard Ferrer Rocca, Maria Martinez, Vanessa Casares, Paula Vera, Matias Flores, Joaquin Amador Amerigo, Maria Pilar Gracia Arnillas, Rosana Munoz Bermudez, Fernando Armestar, Beatriz Catalan, Regina Roig, Laura Raguer, María Dolores Quesada, Emilio Diaz Santos, Gemma Gomà, Alejandro Ubeda, Dra Maria Salgado, Lorena Forcelledo Espina, Emilio Garcia Prieto, Dra Mj Asensio, Dra M. Rodriguez, Emilio Maseda, Alejandro Suarez De La Rica, J. Ignacio Ayestaran, Mariana Novo, Miguel Angel Blasco-Navalpotro, Alberto Orejas Gallego, Fredrik Sjövall, Dzana Spahic, Carl Johan Svensson, Michael Haney, Alicia Edin, Joyce Åkerlund, Lina De Geer, Josef Prazak, Stephan Jakob, Jl Pagani, S. Abed-Maillard, Murat Akova, Abdullah Tarik Aslan, Arif Timuroglu, Sesin Kocagoz, Hulya Kusoglu, Selcuk Mehtap, Solakoğlu Ceyhun, Neriman Defne Altintas, Leyla Talan, Bircan Kayaaslan, Ayşe Kaya Kalem, Ibrahim Kurt, Murat Telli, Barcin Ozturk, Çiğdem Erol, Emine Kubra Dindar Demiray, Sait Çolak, Türkay Akbas, Kursat Gundogan, Ali Sari, Canan Agalar, Onur Çolak, Nurcan N. Baykam, Ozlem O. Akdogan, Mesut Yilmaz, Burcu Tunay, Rumeysa Cakmak, Nese Saltoglu, Ridvan Karaali, Iftihar Koksal, Firdevs Aksoy, Ahmet Eroglu, Kemal Tolga Saracoglu, Yeliz Bilir, Seda Guzeldag, Gulden Ersoz, Guliz Evik, Hulya Sungurtekin, Cansu Ozgen, Cem Erdoğan, Yunus Gürbüz, Nilgün Altin, YasarBayindir, Yasemin Ersoy, Senay Goksu, Ahmet Akyol, Ayse Batirel, Sabahat Cagan Aktas, Andrew Conway Morris, Matthew Routledge, Andrew Conway Morris, Ari Ercole, David Antcliffe, Roceld Rojo, Kate Tizard, Maria Faulkner, Amanda Cowton, Melanie Kent, Ashok Raj, Artemis Zormpa, George Tinaslanidis, Reena Khade, Tomasz Torlinski, Randeep Mulhi, Shraddha Goyal, Manan Bajaj, Marina Soltan, Aimee Yonan, Rachael Dolan, Aimee Johnson, Caroline Macfie, James Lennard, Maie Templeton, Sonia Sousa Arias, Uwe Franke, Keith Hugill, Hollie Angell, Benjamin J. Parcell, Katherine Cobb, Stephen Cole, Tim Smith, Clive Graham, Jaroslav Cerman, Allison Keegan, Jenny Ritzema, Amanda Sanderson, Ashraf Roshdy, Tamas Szakmany, Tom Baumer, Rebecca Longbottom, Daniel Hall, Kate Tatham, S. Loftus, A. Husain, E. Black, S. Jhanji, R. Rao Baikady, Peter Mcguigan, Rachel Mckee, Santhana Kannan, Supriya Antrolikar, Nicholas Marsden, Valentina Della Torre, Dorota Banach, Ahmed Zaki, Matthew Jackson, Moses Chikungwa, Ben Attwood, Jamie Patel, Rebecca E. Tilley, Miss Sally K. Humphreys, Paul Jean Renaud, Anton Sokhan, Yaroslava Burma, Wendy Sligl, Nadia Baig, Lorena McCoshen, Demetrios J. Kutsogiannis, Wendy Sligl, Patricia Thompson, Tayne Hewer, Raihan Rabbani, Shihan Mahmud Redwanul Huq, Rajib Hasan, Mohammad Motiul Islam, Mohan Gurjar, Arvind Baronia, Nikhil Kothari, Ankur Sharma, Saurabh Karmakar, Priya Sharma, Janardan Nimbolkar, Pratit Samdani, R. Vaidyanathan, Noor Ahmedi Rubina, Nikhilesh Jain, Madhumati Pahuja, Ritu Singh, Saurav Shekhar, Syed Nabeel Muzaffar, Ahmad Ozair, Suhail Sarwar Siddiqui, Payel Bose, Avijatri Datta, Darshana Rathod, Mayur Patel, M. K. Renuka, Sailaja K. Baby, Carol Dsilva, Jagadish Chandran, Pralay Ghosh, Sudipta Mukherjee, Kaladhar Sheshala, Krushna Chandra Misra, Saidu Yusuf Yakubu, Euphemia Mgbosoro Ugwu, John O. Olatosi, Ibironke Desalu, Gabriel Asiyanbi, Motunrayo Oladimeji, Olusola Idowu, Fowotade Adeola, Melanie Mc Cree, Ali Adil Ali Karar, Elfayadh Saidahmed, Hytham K. S. Hamid Funding JdW is a senior clinical investigator funded by the Research Foundation Flanders (FWO, Ref. 1881020N). ACM is supported by a Medical Research Council Clinician Scientist Fellowship (MR/ V006118/1). NB received a fellowship grant (Grant number: P4P4PM_194449) from the Swiss National Science Foundation. Research grants were obtained from the European Society of Intensive Care Medicine (ESICM), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP), the Norva Dahlia foundation and the Redcliffe Hospital Private Practice Trust Fund.

Availability of data and material

The datasets used and/or analysed during the current study are available from the OUTCOMEREA organisation on reasonable request.

Author contributions

Alexis Tabah, Niccolò Buetti, Jean-François Timsit, Quentin Staiquly, and Stéphane Ruckly 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. All the authors approved the manuscript in its final format.

Concept and design:

Initial revision of the manuscript:

Niccolò Buetti, François Barbier, Jean-François Timsit and Jeffrey Lipman.

Revision of the manuscript for important intellectual content:

All authors.

Administrative, technical, or material support:

Caroline Dallongeville, Quentin Staiquly, Stéphane Ruckly, and Guy Francois.

Group Information:

The EUROBACT-2 national coordinators, scientific committee and investigators are listed in the electronic supplement.

Additional Contributions:

We thank Guy Francois, Division of Scientific Affairs and Research of the ESICM for his unvaluable assistance in recruiting participating ICUs. We thank the health care workers at each study site, laboratory, and beyond that contributed to the EUROBACT-2 study and acknowledge their work during the initial waves of the COVID-19 pandemic. We thank the patients who participated in the EUROBACT-2 study. We thank Professor Andrea Marshall, PhD, and Doctor Mahesh Ramanan, MBBS, FCICM for proofreading and editing the manuscript.


Stefan Hae!iger, Paula Ungureanu and François-Xavier de Vaujany 1

Opening organizational processes and structures seems to be a more and more central to a contemporary approach to management and organization. In the last decades, this approach changed dramatically from the vertically organised and closed silos of the grand R&D organizations of the 20 th century to a collaborative, joint, user-led, indeed, inverted "rm that characterizes platforms [START_REF] Benzell | How apis create growth by inverting the[END_REF]. Where once all resources were allocated internally and spillovers cast as the antithesis to successful competition today's managerial tenets include pre-emptive generosity, contributions to public goods, and the integration of consumers in production processes.

Organization studies and social studies at large invite both scholars and practitioners to open their ways of thinking and acting. Open innovation [START_REF] Chesbrough | Open innovation: Where we've been and where we're going[END_REF][START_REF] Bogers | e open innovation research landscape: Established perspectives and emerging themes across di(erent levels of analysis[END_REF], knowledge #ows across communities and organizations (Hae#iger, Von Krogh and Spaeth, 2008), open research and inquiries (de Vaujany and Heimstädt, 2022) all contribute to a new principle of openness [START_REF] Splitter | Openness as Organizing principle: introduction to the special issue[END_REF] that drives strategy and leadership [START_REF] Hautz | Open strategy: Dimensions, dilemmas, dynamics[END_REF].

Opening is a spatial invitation. It is a call to create more permeability in organizational boundaries or even, to overcome them to potentially let in new actors, techniques or experience. It is also a deeply temporal claim. Any lived pasts or dreamed and anticipated futures should be likely to enter into the organizing process. Open organizing is a deep, resonant, #uid mode of collective activity. While spatial dimensions appear in topics of new work and how o%ces are structured, more virtual dimensions drive the opening or the reversal of openness in strategy, such as the #ow of knowledge and experience on one side, and the inclusivity of decision making on the other side (Hae#iger, 2019).

As shown with this thematic issue of the JOCO, openness carries wider implications that touch upon social and political spheres. Our approaches to coordination, allocation of resources, our views of value and business models, are deeply renewed by this move. Crowds are more expected to feed the innovation process, and even to disrupt it. Likewise, citizen and open sciences are more and more expected to enrich and sometimes, part with traditional ways of doing research. Emergent technology also stimulates the imaginative transformation of present conditions into future visions of disruptive openness. Arti"cial intelligence prospects a world where the machine will be able to generate innovation beyond human ability [START_REF] Faraj | Working and organizing in the age of the learning algorithm[END_REF]) and blockchain technologies promise to facilitate an integrated worldwide data warehouse where any format of data can be shared and understood by any device over any network [START_REF] Jacobetty | Blockchain imaginaries and their metaphors: Organising principles in decentralised digital technologies[END_REF]. Immersive and augmented reality technologies promise to transform the way we work and interact by translating into our daily environments objects, people, and places that are either distant or do not yet exist [START_REF] Dincelli | Immersive virtual reality in the age of the Metaverse: A hybrid-narrative review based on the technology a(ordance perspective[END_REF]. 'ese promises transcend institutionalized boundaries between physical and virtual realities, humans and machines, markets, states, professions and communities, to convey the idealized image of a technocratic world that will be free, open, progressive, even transcendent.

'is has also multiple consequences for work practices and ways of organizing them. Work itself can now happen openly from anywhere at any time [START_REF] Cnossen | e street and organization studies[END_REF]. People can now be remote workers or digital nomads. 'eir work is not anymore an activity bounded within an organization, a recurrent and routine here and now. It is more and more an open, #uid and ambiguous temporality. And novelty as part of a product and service can now happen anywhere, anytime. 'e recent algorithmic phenomena and models in our society promise to establish radically new forms of organization based on automation and decentralization such as peerto-peer knowledge communities, AI-powered holacracies and decentralized platform ecosystems where code becomes the 'law' (Lessig, 2000) and knowledge and practices pertaining to traditional "elds of expertise are subverted, transformed or even abolished [START_REF] Burrell | e society of algorithms[END_REF]Zubo(, 2019). Innovation, in particular, has changed dramatically in the platform society. Multiple actors involved in innovation processes operate across organizational boundaries within interdependent relations which bring together multiple forms of organization; Consequently, when success or failure occur in such systems, measuring and attributing performance becomes an uncertain or highly debated endeavour [START_REF] Shipilov | Integrating research on interorganizational networks and ecosystems[END_REF].For our democracies and our societies which have largely relied on productive activities on the here and now of a place (for employees, for customers, for citizens…) and of clear-cut organizational forms, this has for sure radical implications which will be explored in the thematic issue.

While business may or may not be perceived as core to society and democracy, a number of fundamental changes linked to openness in innovation and strategy may translate to impact the societal and political spheres more and more. 'e promise of Castells' network society take the everyday and mundane forms of communication platforms such as WhatsApp or X and civil discourse shapes and is shaped by the corporate decisions around application programming interfaces. Who gets to in#uence a democratic discourse with nudges and advertisement? Who gets to program extensions and modi"cations of programs used to share news or scienti"c "ndings?

Traditional media have been gradually losing their role as public-opinion makers to social media, which have been long described as an emerging global agora for collective decisions [START_REF] Castells | Networks of outrage and hope: Social movements in the Internet age[END_REF][START_REF] Etter | Social media and the formation of organizational reputation[END_REF]). Yet the last decades of public scandals regarding ignorance and manipulation have su*ested that the idealized visions of openness in social media co-exist side-by-side with polarization, social division and erosion of democratic institutions. Similarly, emerging technologies which promise to emancipate in the future have been shown to enslave, constrain or even humiliate human dignity in the present. Activists take on platforms they accuse of abusing workers by manipulation and surveillance and consumers protest against algorithms that store their preferences and use them for and against them to optimise service delivery and pricing. 'e gig economy where everyone can work at any time and any place has become a daunting place for mental health (e.g. [START_REF] Petriglieri | Agony and ecstasy in the gig economy: Cultivating holding environments for precarious and personalized work identities[END_REF] and expanded surveillance increasingly links political views with employment opportunities and discriminatory business practices.

We may be under a grave risk of underestimating in#uences that emerge from points of view fundamentally opposed to democracy and human rights, in fact facing alternative truths we may be swayed into worldviews that are murderous and disrespectful of any human rights and freedoms. If openness turns to an indiscriminate endorsement of any idea as long as it comes with money and resources, then openness is likely to hurt democracy and end it.

Is the inverted "rm becoming the inverted democracy? Does a society increasingly draw on resources from the outside and does the openness of a society pose risks that are critical for its sustained openness and sustainability? It appeared always as unquestionable that closed societies tend to lose out, on global trade, culture, and the opportunities for their citizens. What are the downsides of openness for a society and have we understood these downsides in times of increasingly fast and uncontrollable knowledge #ows?

In organizations, openness does not appear to seal its own fate as far as we know. While irreversible in the short run, open strategy holds the potential for changing paths and pivoting to new and extended purposes for the organization with the inclusion into decision making of stakeholders beyond the owners. To deal with the paradoxes of openness, we thus su*est a renewed attention to temporal and spatial dimensions (see also DeVaujany et al.,2023, this journal, Ungureanu, 2023). For instance, what is the relationship between idealized visions of future open worlds and the ongoing trials and errors through which openness is experimented in our present's organizations, communities and institutions? How are ongoing processes of spatial and temporal strategizing shaping current institutions and organizations? Speci"cally, as we strategize about new socio-technical arrangements, how are we moving towards aspirations for a better world or getting resucked into old forms of organizational power, control and surveillance? To celebrate local diversity, how can we continue to study socially situated work practices while acknowledging globalization and virtualization trends? Most importantly, which are the guideposts that we, as individuals and as collectives, might follow as we traverse an increasingly complex world made of social, technological and environmental challenges? What are the capitalist safeguards and how do such safeguards translate to democracies and society at large? While bankruptcy laws protect citizens we have little in store to protect failing governments and institutions if openness over#ows and turns against them. We hope this issue inspires further and wider thoughts in social sciences as to the ends and risks of openness with a pragmatic and critical eye.


Mark Lester

Beatriz Sanchez-Cano

Daniel Potts

Rob Lillis

Roberto I Orosei

Bruce Campbell

Olivier Witasse

Hermann Opgenoorth

Steve Milan

Marco Cartacci

A Statistical Analysis of Radar Blackouts at Mars: MARSIS, SHARAD and MAVEN Observations

A Statistical Analysis of Radar Blackouts at Mars: MARSIS, SHARAD and MAVEN Observations

We present an analysis of radar blackouts observed by MARSIS on Mars Express and SHARAD on Mars Reconnaissance Orbiter for the interval 2006 -2017. The period of interest encompasses the extended solar minimum between solar cycles 23 and 24 as well as the solar maximum of cycle 24. Blackouts have been identified by eye through scanning daily plots of the surface reflection for both radars. A blackout occurs when, for no apparent instrumental reason, the surface reflection normally expected is either not observed (total) or when the surface reflection is seen for only part of the orbit or the surface reflection is both weaker and spread over a significant time delay (partial). Such blackouts are caused by enhanced ionisation at altitudes below the main ionospheric electron density peak resulting in increased absorption of the radar signal. There are more occurrences observed by MARSIS than SHARAD, which is expected due to the lower absorption at the higher operating frequency of SHARAD. We also observe more blackouts during solar maximum than solar minimum. Indeed, there are no total blackouts during the extended solar minimum, although both radars do have partial blackouts. There is no apparent relationship between blackout occurrence and crustal magnetic fields. Following previous work, which has indicated that solar energetic particles, specifically electrons are responsible for the enhanced ionisation in the atmosphere, we also present the analysis of the MAVEN SEP electrons between 20 keV and 2 MeV during events when all three spacecraft were operational. We find that the SEP electron flux-energy relationship is much enhanced during the total blackouts, in particular where both radars are impacted, while for partial blackouts the flux-energy spectrum is closer to those from orbits where no blackout occurs. We also find that for certain events, the average spectrum which result in a blackout is particularly enhanced at the higher energy end of the spectrum, above 50 keV. The average spectra from each condition is presented. We conclude that there is a higher probability of a radar blackout during solar maximum, that crustal magnetic fields play no apparent role in the their observational occurrence, that the higher energy (< 50 keV) electrons are responsible, and that for events where both radars observe a radar blackout the SEP electron fluxes are at their highest. ! !

How to cite

:

  Lester, M., Sanchez-Cano, B., Potts, D., Lillis, R., Orosei, R. I., Campbell, B., Witasse, O., Opgenoorth, H., Milan, S., Cartacci, M., Bernardini, F., Perry, M., Putzig, N., Blelly, P.-L., and Leblanc, F.: A Statistical Analysis of Radar Blackouts at Mars: MARSIS, SHARAD and MAVEN Observations, Europlanet Science Congress 2020, online, 21 Sep-9 Oct 2020, EPSC2020-687, https://doi.org /10.5194/epsc2020-687, 2020.