the EUROBACT-2 international cohort study

Funding JdW is a senior clinical investigator funded by the Research Foundation Flan ders (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 Founda tion. 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 Redclife Hospital Private Practice Trust Fund.PURPOSE: In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. METHODS: We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. RESULTS: 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28. CONCLUSIONS: HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes.publishersversionpublishe

Treatment of positive catheter tip culture without bloodstream infections in critically ill patients. A case-cohort study from the OUTCOMEREA network

International audiencePurpose: This study aimed to evaluate the impact on subsequent infections and mortality of an adequate antimicrobial therapy within 48 h after catheter removal in intensive care unit (ICU) patients with positive catheter tip culture.Methods: We performed a retrospective analysis of prospectively collected data from 29 centers of the OUTCOMEREA network. We developed a propensity score (PS) for adequate antimicrobial treatment, based on expert opinion of 45 attending physicians. We conducted a 1:1 case-cohort study matched on the PS score of being adequately treated. A PS-matched subdistribution hazard model was used for detecting subsequent infections and a PS-matched Cox model was used to evaluate the impact of antibiotic therapy on mortality.Results: We included 427 patients with a catheter tip culture positive with potentially pathogenic microorganisms. We matched 150 patients with an adequate antimicrobial therapy with 150 controls. In the matched population, 30 (10%) subsequent infections were observed and 62 patients died within 30 days. Using subdistribution hazard models, the daily risk to develop subsequent infection up to Day-30 was similar between treated and non-treated groups (subdistribution hazard ratio [sHR] 1.08, 95% confidence interval [CI] 0.62-1.89, p = 0.78). Using Cox proportional hazard models, the 30-day mortality risk was similar between treated and non-treated groups (HR 0.89, 95% CI 0.45-1.74, p = 0.73).Conclusions: Antimicrobial therapy was not associated with decreased risk of subsequent infection or death in short-term catheter tip colonization in critically ill patients. Antibiotics may be unnecessary for positive catheter tip cultures

Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study.

BACKGROUND Hospital-acquired bloodstream infections are common in the intensive care unit (ICU) and have a high mortality rate. Patients with cirrhosis are especially susceptible to infections, yet there is a knowledge gap in the epidemiological distinctions in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that cirrhotic patients, present a trend towards more gram-positive infections, and especially enterococcal infections. This study aims to describe epidemiological differences in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients hospitalized in the ICU regarding infection sources, microorganisms and mortality. METHODS Using prospective Eurobact-2 international cohort study data, we compared hospital-acquired bloodstream infections sources and microorganisms in cirrhotic and non-cirrhotic patients. The association between Enterococcus faecium and cirrhosis was studied using a multivariable mixed logistic regression. The association between cirrhosis and mortality was assessed by a multivariable frailty Cox model. RESULTS Among the 1059 hospital-acquired bloodstream infections patients included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream infection source in cirrhotic patients was primarily abdominal (35.6%), while it was pulmonary (18.9%) for non-cirrhotic (p < 0.01). Gram-positive hospital-acquired bloodstream infections accounted for 42.3% in cirrhotic patients compared to 33.2% in non-cirrhotic patients (p = 0.02). Hospital-acquired bloodstream infections in cirrhotic patients were most frequently caused by Klebsiella spp (16.5%), coagulase-negative Staphylococci (13.7%) and E. faecium (11.5%). E. faecium bacteremia was more frequent in cirrhotic patients (11.5% versus 4.5%, p < 0.01). After adjusting for possible confounding factors, cirrhosis was associated with higher E. faecium hospital-acquired bloodstream infections risk (Odds ratio 2.5, 95% CI 1.3-4.5, p < 0.01). Cirrhotic patients had increased mortality compared to non-cirrhotic patients (Hazard Ratio 1.3, 95% CI 1.01-1.7, p = 0.045). CONCLUSIONS Critically ill cirrhotic patients with hospital-acquired bloodstream infections exhibit distinct epidemiology, with more Gram-positive infections and particularly Enterococcus faecium

Shortening antibiotic therapy duration for hospital-acquired bloodstream infections in critically ill patients : a causal inference model from the international EUROBACT-2 database

INTRODUCTION: Hospital-acquired bloodstream infections (HA-BSIs) are severe and require antibiotic therapy. In non-complicated BSIs, shortened therapy reduces side effects without compromising efficacy. The impact of shortened antibiotic therapy in HA-BSI critically ill patients without indication of prolonged therapy requires further evaluation. METHODS: Using the international prospective EUROBACT-2 cohort, we compared shortened (7-10 days) versus long (14-21 days) treatment durations in ICU patients eligible for shortened therapy. Patients without antibiotic therapy within 3 days after HA-BSI occurrence or requiring prolonged therapy (due to infection source, microorganism, or clinical deterioration) were excluded. Treatment failure, defined as death, persistent infection, or subsequent infectious complications by Day 28, was assessed using an inverse-probability of treatment weighted (IPTW) logistic regression. RESULTS: Among 2600 patients, 550 were eligible for shortened treatment, 213 received short, and 337 received long treatment. The most common infection source was intravascular catheters (33%), most common microorganisms were Enterobacterales (39%). Patients with long treatment were more frequently infected with Staphylococcus aureus (11% vs. 5.6%, p = 0.025) or difficult-to-treat microorganisms (23% vs. 7%, p < 0.001), and received more commonly combination therapy (46% vs. 30%, p < 0.001). Short treatment was associated with reduced 28-day treatment failure (OR 0.64, 95% CI 0.44-0.93, p = 0.019), mainly due to reduction in subsequent infectious complications (OR 0.58, 95% CI 0.37-0.91, p = 0.018). Mortality (OR 0.92 [95% CI 0.59, 1.43], p = 0.7) and persistent infection rates (OR 0.47 [95% CI 0.17, 1.14], p = 0.12) were similar. CONCLUSIONS: In selected ICU patients with HA-BSI, shortened antibiotic treatment might be considered. Eurobact2 was a prospective international cohort study, registered in ClinicalTrials.org (NCT03937245)

Variability in forgoing life-sustaining treatment practices in critically Ill patients with hospital-acquired bloodstream infections: a secondary analysis of the EUROBACT-2 international cohort

Background: The decision to forgo life-sustaining treatment in intensive care units (ICUs) is influenced by ethical, cultural, and medical factors. This study focuses on a population of patients with hospital-acquired bloodstream infections (HABSI) to investigate the association between patient, pathogen, center and country-level factors and these decisions. Methods: We analyzed data from the EUROBACT-2 study (June 2019-January 2021) from 265 centers worldwide, focusing on non-COVID-19 patients who died in the hospital or within 28 days after HABSI. We assessed whether death was preceded by a decision to forgo life-sustaining treatment, examining country, center, patient, and pathogen variables. To assess the association of each potentially important variable with the decision to forgo life-sustaining treatment, univariable mixed logistic regression models with a random center effect were performed. Results: Among 1589 non-COVID-19 patients, 519 (32.7%) died, with 191 (36.8%) following a decision to forgo life-sustaining treatment. Significant geographical differences were observed, with no reported decisions to forgo life-sustaining treatment in African countries and fewer in the Middle East compared to Western Europe, Australia, and Asia. Once a center effect was considered, only health expenditure (Odds ratio 1.79, 95%CI: 1.45-2.21, p &lt; 0.01) and age (Odds ratio 1.02, 95%CI: 1.002-1.05, p = 0.03) were significantly associated with decisions to forgo life-sustaining treatment, while other patient and pathogen factors were not. Conclusion: Economic and regional disparities significantly impact end-of-life decision-making in ICUs. Global policies should consider these disparities to ensure equitable end-of-life care practices.</p

Corticosteroids for severe acute exacerbations of chronic obstructive pulmonary disease in intensive care: From the French OUTCOMEREA cohort.

IntroductionAcute exacerbation of chronic obstructive pulmonary disease (COPD) is a frequent cause of intensive care unit (ICU) admission. However, data are scarce and conflicting regarding the impact of systemic corticosteroid treatment in critically ill patients with acute exacerbation of COPD. The aim of the study was to assess the impact of systemic corticosteroids on the occurrence of death or need for continuous invasive mechanical ventilation at day 28 after ICU admission.MethodsIn the OutcomeReaTM prospective French national ICU database, we assessed the impact of corticosteroids at admission (daily dose ≥ 0.5 mg/kg of prednisone or equivalent during the first 24 hours ICU stay) on a composite outcome (death or invasive mechanical ventilation) using an inverse probability treatment weighting.ResultsBetween January 1, 1997 and December 31, 2018, 391 out of 1,247 patients with acute exacerbations of COPDs received corticosteroids at ICU admission. Corticosteroids improved the main composite endpoint (OR = 0.70 [0.49; 0.99], p = 0.044. However, for the subgroup of most severe COPD patients, this did not occur (OR = 1.12 [0.53; 2.36], p = 0. 770). There was no significant impact of corticosteroids on rates of non-invasive ventilation failure, length of ICU or hospital stay, mortality or on the duration of mechanical ventilation. Patients on corticosteroids had the same prevalence of nosocomial infections as those without corticosteroids, but more glycaemic disorders.ConclusionUsing systemic corticosteroids for acute exacerbation of COPD at ICU admission had a positive effect on a composite outcome defined by death or need for invasive mechanical ventilation at day 28

Shortening antibiotic therapy duration for hospital-acquired bloodstream infections in critically ill patients : a causal inference model from the international EUROBACT-2 database

Introduction: Hospital-acquired bloodstream infections (HA-BSIs) are severe and require antibiotic therapy. In non-complicated BSIs, shortened therapy reduces side effects without compromising efficacy. The impact of shortened antibiotic therapy in HA-BSI critically ill patients without indication of prolonged therapy requires further evaluation. Methods: Using the international prospective EUROBACT-2 cohort, we compared shortened (7-10 days) versus long (14-21 days) treatment durations in ICU patients eligible for shortened therapy. Patients without antibiotic therapy within 3 days after HA-BSI occurrence or requiring prolonged therapy (due to infection source, microorganism, or clinical deterioration) were excluded. Treatment failure, defined as death, persistent infection, or subsequent infectious complications by Day 28, was assessed using an inverse-probability of treatment weighted (IPTW) logistic regression. Results: Among 2600 patients, 550 were eligible for shortened treatment, 213 received short, and 337 received long treatment. The most common infection source was intravascular catheters (33%), most common microorganisms were Enterobacterales (39%). Patients with long treatment were more frequently infected with Staphylococcus aureus (11% vs. 5.6%, p = 0.025) or difficult-to-treat microorganisms (23% vs. 7%, p &lt; 0.001), and received more commonly combination therapy (46% vs. 30%, p &lt; 0.001). Short treatment was associated with reduced 28-day treatment failure (OR 0.64, 95% CI 0.44-0.93, p = 0.019), mainly due to reduction in subsequent infectious complications (OR 0.58, 95% CI 0.37-0.91, p = 0.018). Mortality (OR 0.92 [95% CI 0.59, 1.43], p = 0.7) and persistent infection rates (OR 0.47 [95% CI 0.17, 1.14], p = 0.12) were similar. Conclusions: In selected ICU patients with HA-BSI, shortened antibiotic treatment might be considered. Eurobact2 was a prospective international cohort study, registered in ClinicalTrials.org (NCT03937245).</p

Presentation, management, and outcomes of older compared to younger adults with hospital-acquired bloodstream infections in the intensive care unit : a multicenter cohort study

Purpose: Older adults admitted to the intensive care unit (ICU) usually have fair baseline functional capacity, yet their age and frailty may compromise their management. We compared the characteristics and management of older (≥ 75 years) versus younger adults hospitalized in ICU with hospital-acquired bloodstream infection (HA-BSI). Methods: Nested cohort study within the EUROBACT-2 database, a multinational prospective cohort study including adults (≥ 18 years) hospitalized in the ICU during 2019-2021. We compared older versus younger adults in terms of infection characteristics (clinical signs and symptoms, source, and microbiological data), management (imaging, source control, antimicrobial therapy), and outcomes (28-day mortality and hospital discharge). Results: Among 2111 individuals hospitalized in 219 ICUs with HA-BSI, 563 (27%) were ≥ 75 years old. Compared to younger patients, these individuals had higher comorbidity score and lower functional capacity; presented more often with a pulmonary, urinary, or unknown HA-BSI source; and had lower heart rate, blood pressure and temperature at presentation. Pathogens and resistance rates were similar in both groups. Differences in management included mainly lower rates of effective source control achievement among aged individuals. Older adults also had significantly higher day-28 mortality (50% versus 34%, p &lt; 0.001), and lower rates of discharge from hospital (12% versus 20%, p &lt; 0.001) by this time. Conclusions: Older adults with HA-BSI hospitalized in ICU have different baseline characteristics and source of infection compared to younger patients. Management of older adults differs mainly by lower probability to achieve source control. This should be targeted to improve outcomes among older ICU patients.</p

Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study.

Funder: University of GenevaBACKGROUND: Hospital-acquired bloodstream infections are common in the intensive care unit (ICU) and have a high mortality rate. Patients with cirrhosis are especially susceptible to infections, yet there is a knowledge gap in the epidemiological distinctions in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that cirrhotic patients, present a trend towards more gram-positive infections, and especially enterococcal infections. This study aims to describe epidemiological differences in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients hospitalized in the ICU regarding infection sources, microorganisms and mortality. METHODS: Using prospective Eurobact-2 international cohort study data, we compared hospital-acquired bloodstream infections sources and microorganisms in cirrhotic and non-cirrhotic patients. The association between Enterococcus faecium and cirrhosis was studied using a multivariable mixed logistic regression. The association between cirrhosis and mortality was assessed by a multivariable frailty Cox model. RESULTS: Among the 1059 hospital-acquired bloodstream infections patients included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream infection source in cirrhotic patients was primarily abdominal (35.6%), while it was pulmonary (18.9%) for non-cirrhotic (p < 0.01). Gram-positive hospital-acquired bloodstream infections accounted for 42.3% in cirrhotic patients compared to 33.2% in non-cirrhotic patients (p = 0.02). Hospital-acquired bloodstream infections in cirrhotic patients were most frequently caused by Klebsiella spp (16.5%), coagulase-negative Staphylococci (13.7%) and E. faecium (11.5%). E. faecium bacteremia was more frequent in cirrhotic patients (11.5% versus 4.5%, p < 0.01). After adjusting for possible confounding factors, cirrhosis was associated with higher E. faecium hospital-acquired bloodstream infections risk (Odds ratio 2.5, 95% CI 1.3-4.5, p < 0.01). Cirrhotic patients had increased mortality compared to non-cirrhotic patients (Hazard Ratio 1.3, 95% CI 1.01-1.7, p = 0.045). CONCLUSIONS: Critically ill cirrhotic patients with hospital-acquired bloodstream infections exhibit distinct epidemiology, with more Gram-positive infections and particularly Enterococcus faecium

Variability in forgoing life-sustaining treatment practices in critically Ill patients with hospital-acquired bloodstream infections : a secondary analysis of the EUROBACT-2 international cohort

Background The decision to forgo life-sustaining treatment in intensive care units (ICUs) is influenced by ethical, cultural, and medical factors. This study focuses on a population of patients with hospital-acquired bloodstream infections (HABSI) to investigate the association between patient, pathogen, center and country-level factors and these decisions. Methods We analyzed data from the EUROBACT-2 study (June 2019-January 2021) from 265 centers worldwide, focusing on non-COVID-19 patients who died in the hospital or within 28 days after HABSI. We assessed whether death was preceded by a decision to forgo life-sustaining treatment, examining country, center, patient, and pathogen variables. To assess the association of each potentially important variable with the decision to forgo life-sustaining treatment, univariable mixed logistic regression models with a random center effect were performed. Results Among 1589 non-COVID-19 patients, 519 (32.7%) died, with 191 (36.8%) following a decision to forgo life-sustaining treatment. Significant geographical differences were observed, with no reported decisions to forgo life-sustaining treatment in African countries and fewer in the Middle East compared to Western Europe, Australia, and Asia. Once a center effect was considered, only health expenditure (Odds ratio 1.79, 95%CI: 1.45-2.21, p < 0.01) and age (Odds ratio 1.02, 95%CI: 1.002-1.05, p = 0.03) were significantly associated with decisions to forgo life-sustaining treatment, while other patient and pathogen factors were not. Conclusion Economic and regional disparities significantly impact end-of-life decision-making in ICUs. Global policies should consider these disparities to ensure equitable end-of-life care practices.Background The decision to forgo life-sustaining treatment in intensive care units (ICUs) is influenced by ethical, cultural, and medical factors. This study focuses on a population of patients with hospital-acquired bloodstream infections (HABSI) to investigate the association between patient, pathogen, center and country-level factors and these decisions. Methods We analyzed data from the EUROBACT-2 study (June 2019-January 2021) from 265 centers worldwide, focusing on non-COVID-19 patients who died in the hospital or within 28 days after HABSI. We assessed whether death was preceded by a decision to forgo life-sustaining treatment, examining country, center, patient, and pathogen variables. To assess the association of each potentially important variable with the decision to forgo life-sustaining treatment, univariable mixed logistic regression models with a random center effect were performed. Results Among 1589 non-COVID-19 patients, 519 (32.7%) died, with 191 (36.8%) following a decision to forgo life-sustaining treatment. Significant geographical differences were observed, with no reported decisions to forgo life-sustaining treatment in African countries and fewer in the Middle East compared to Western Europe, Australia, and Asia. Once a center effect was considered, only health expenditure (Odds ratio 1.79, 95%CI: 1.45-2.21, p < 0.01) and age (Odds ratio 1.02, 95%CI: 1.002-1.05, p = 0.03) were significantly associated with decisions to forgo life-sustaining treatment, while other patient and pathogen factors were not. Conclusion Economic and regional disparities significantly impact end-of-life decision-making in ICUs. Global policies should consider these disparities to ensure equitable end-of-life care practices.A