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

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 &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

Effect of adequacy of empirical antibiotic therapy for hospital-acquired bloodstream infections on intensive care unit patient prognosis: a causal inference approach using data from the Eurobact2 study.

OBJECTIVES: Hospital-acquired bloodstream infections (HA-BSI) in the intensive care unit (ICU) are common life-threatening events. We aimed to investigate the association between early adequate antibiotic therapy and 28-day mortality in ICU patients who survived at least 1 day after the onset of HA-BSI. METHODS: We used individual data from a prospective, observational, multicentre, and intercontinental cohort study (Eurobact2). We included patients who were followed for ≥1 day and for whom time-to-appropriate treatment was available. We used an adjusted frailty Cox proportional-hazard model to assess the effect of time-to-treatment-adequacy on 28-day mortality. Infection- and patient-related variables identified as confounders by the Directed Acyclic Graph were used for adjustment. Adequate therapy within 24 hours was used for the primary analysis. Secondary analyses were performed for adequate therapy within 48 and 72 hours and for identified patient subgroups. RESULTS: Among the 2418 patients included in 330 centres worldwide, 28-day mortality was 32.8% (n = 402/1226) in patients who were adequately treated within 24 hours after HA-BSI onset and 40% (n = 477/1192) in inadequately treated patients (p < 0.01). Adequacy within 24 hours was more common in young, immunosuppressed patients, and with HA-BSI due to Gram-negative pathogens. Antimicrobial adequacy was significantly associated with 28-day survival (adjusted Hazard Ratio (aHR), 0.83; 95% CI, 0.72-0.96; p 0.01). The estimated population attributable fraction of 28-day mortality of inadequate therapy was 9.15% (95% CI, 1.9-16.2%). DISCUSSION: In patients with HA-BSI admitted to the ICU, the population attributable fraction of 28-day mortality of inadequate therapy within 24 hours was 9.15%. This estimate should be used when hypothesizing the possible benefit of any intervention aiming at reducing the time-to-appropriate antimicrobial therapy in HA-BSI

Risk Factors for Mortality Among Older Adults with Hospital-Acquired Bloodstream Infections in the Intensive Care Unit : A Multicenter Cohort Study

Introduction: We aimed to investigate risk factors for mortality among older adults (≥ 75 years) with hospital-acquired bloodstream infections (HA-BSI) in the intensive care unit (ICU). Methods: We included patients aged ≥ 75 years with HA-BSI in ICU from the EUROBACT-2 cohort (2019-2021). Univariable and multivariable analyses were conducted to identify predictors of 28-day mortality. Results: The cohort included 563 patients (median age 80, 39% women). Mortality at 28 day was 50%. Factors associated with mortality in multivariate analysis were admission due to COVID-19, failure to achieve source control, and higher SOFA. Among older adults with Gram-negative BSI, corticosteroid administration for septic shock was an additional factor. Among functionally independent patients, age itself was not associated with mortality. Conclusions: HA-BSI in older adults in ICU are associated with high mortality. Inadequate source control is a significant modifiable risk factor. The use of corticosteroids in ICU management of older adults should be further investigated.</p

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections

Purpose: The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI). Methods: We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators. Results: Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality. Conclusion: Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.</p

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections.

PURPOSE: The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI). METHODS: We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators. RESULTS: Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality. CONCLUSION: Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.Clinician Scientist Fellowship grant number: MR/V006118/1

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections.

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: European Society of Clinical Microbiology and Infectious Diseases; doi: http://dx.doi.org/10.13039/501100001704Funder: Norva Dahlia foundation and the Redcliffe Hospital Private Practice Trust FundFunder: University of GenevaPURPOSE: The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI). METHODS: We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators. RESULTS: Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality. CONCLUSION: Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.Clinician Scientist Fellowship grant number: MR/V006118/1

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