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

Hannah Wozniak, Alexis Tabah, François Barbier, Stéphane Ruckly, Ambre Loiodice, Murat Akova, Marc Leone, Andrew Conway Morris, Matteo Bassetti, Kostoula Arvaniti, et al.

<figure><img src="image_1.png" /></figure>

## To cite this version:

Hannah Wozniak, Alexis Tabah, François Barbier, Stéphane Ruckly, Ambre Loiodice, et al. Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study. Annals of Intensive Care, 2024, 14, 10.1186/s13613-024-01299-x. hal-04598368

HAL Id: hal-04598368

https://u-paris.hal.science/hal-04598368

Submitted on 3 Jun 2024

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
# Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study

Hannah Wozniak, Alexis Tabah, François Barbier, Stéphane Ruckly, Ambre Loiodice, Murat Akova, Marc Leone, Andrew Conway Morris, Matteo Bassetti, Kostoula Arvaniti, et al.

<figure><img src="image_1.png" /></figure>

## To cite this version:

Hannah Wozniak, Alexis Tabah, François Barbier, Stéphane Ruckly, Ambre Loiodice, et al. Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study. Annals of Intensive Care, 2024, 14 (1), pp.70. 10.1186/s13613-024-01299-x. hal-04598368

HAL Id: hal-04598368

https://u-paris.hal.science/hal-04598368v1

Submitted on 3 Jun 2024

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
RESEARCH

Open Access

<figure><img src="image_3.png" /></figure>

Check for
updates

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

Hannah Wozniak<sup>1,2*</sup> ◐, Alexis Tabah<sup>3,4,5,6</sup>, François Barbier<sup>7</sup>, Stéphane Ruckly<sup>8,9</sup>, Ambre Loiodice<sup>9</sup>, Murat Akova<sup>10</sup>, Marc Leone<sup>11</sup>, Andrew Conway Morris<sup>12,13,14</sup>, Matteo Bassetti<sup>15</sup>, Kostoula Arvaniti<sup>16</sup>, Ricard Ferrer<sup>17</sup>, Liesbet de Bus<sup>18,19</sup>, Jose Artur Paiva<sup>20,21</sup>, Hendrik Bracht<sup>22</sup>, Adam Mikstacki<sup>23,24</sup>, Adel Alsisi<sup>25,26</sup>, Liana Valeanu<sup>27</sup>, Josef Prazak<sup>28</sup>, Jean-François Timsit<sup>29,30</sup>, Niccolò Buetti<sup>29,31</sup> and on behalf of the EUROBACT-2 Study Group, ESICM, ESCMID ESGCIP and the OUTCOMEREA Network

**Abstract**

**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*

Full list of author information is available at the end of the article

<figure><img src="image_4.png" /></figure>

<footnote>*Correspondence:
Hannah Wozniak
Hannah.wozniak@hcuge.ch</footnote>
RESEARCH

Open Access

<figure><img src="image_3.png" /></figure>

Check for
updates

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

Hannah Wozniak<sup>1,2*</sup> ◐, Alexis Tabah<sup>3,4,5,6</sup>, François Barbier<sup>7</sup>, Stéphane Ruckly<sup>8,9</sup>, Ambre Loiodice<sup>9</sup>, Murat Akova<sup>10</sup>, Marc Leone<sup>11</sup>, Andrew Conway Morris<sup>12,13,14</sup>, Matteo Bassetti<sup>15</sup>, Kostoula Arvaniti<sup>16</sup>, Ricard Ferrer<sup>17</sup>, Liesbet de Bus<sup>18,19</sup>, Jose Artur Paiva<sup>20,21</sup>, Hendrik Bracht<sup>22</sup>, Adam Mikstacki<sup>23,24</sup>, Adel Alsisi<sup>25,26</sup>, Liana Valeanu<sup>27</sup>, Josef Prazak<sup>28</sup>, Jean-François Timsit<sup>29,30</sup>, Niccolò Buetti<sup>29,31</sup> and on behalf of the EUROBACT-2 Study Group, ESICM, ESCMID ESGCIP and the OUTCOMEREA Network

**Abstract**

**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*

Full list of author information is available at the end of the article

<figure><img src="image_4.png" /></figure>

<footnote>*Correspondence:
Hannah Wozniak
Hannah.wozniak@hcuge.ch</footnote>
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*.

## Introduction

Hospital-acquired bloodstream infections (HABSIs) are frequent in the intensive care unit (ICU) and are associated with a high mortality [1, 2]. Cirrhotic patients are vulnerable and susceptible to hospital-acquired infections, which can affect as many as 43–59% of patients in the ICU [3–7]. Bloodstream infections have been shown to be ten times more frequent in cirrhotic patients and are associated with poor outcomes including acute on chronic liver failure, acute kidney injury, encephalopathy and mortality [3–12]. The majority of infecting bacteria found in patients with cirrhosis are Gram-negative; however, there has been an increase in the prevalence of Gram-positive bacteria with concerns for enterococcal infection [10, 13]. Treatment options in patients with liver disease are challenging for several reasons. First, the pharmacokinetics of antibiotics change with liver disease due to several physiological abnormalities such as hypoalbuminemia, altered liver and renal functions [8, 14]. Second, previous studies have shown a possible association between cirrhosis, colonization and infection by antimicrobial-resistant bacteria as well as higher rates of enterococcal infections [7, 10, 11, 15, 16]. Guidelines for empirical treatment of hospital-acquired infections in cirrhotic patients vary considerably across countries, with third generation cephalosporins, piperacillin-tazobactam or carbapenem being recommended according to local antibiotic resistance data [17, 18]. The 2018 European association for the study of the Liver (EASL) guidelines suggest considering Gram-positive coverage in cases of hospital-acquired infections [17, 18]. The question arises whether extended coverage for Gram-positive and resistant Gram-negative bacteria should be recommended as a first-line treatment in the critically ill cirrhotic patients.

Epidemiological knowledge about the microorganisms responsible for HABSI in cirrhotic patients, their sources and the patient's outcome in the ICU are scarce and no large comparison of the characteristics of these patients with a non-cirrhotic group has previously been performed [4, 8–11, 19]. The objectives of this study were to describe the differences in the epidemiology of HABSI, with particular attention to *E. faecium* infections, between cirrhotic and non-cirrhotic patients in terms of patients' characteristics, source of infection, microorganism distribution and mortality using a large multicontinental database.

## Methods

### Setting

The Eurobact-2 study was a prospective observational international cohort study conducted between August 2019 and June 2021 [2, 20].

A total of 333 centers participated in the study which was registered in ClinicalTrials.org (NCT03937245). The study was reported in accordance with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines [21].

Details regarding the methodology can be found in the previously reported Eurobact-2 study [2]. The study was approved by the ethics Committee of the Royal Brisbane & Women's Hospital Human Research (LNR/2019/QRBW/48,376). Each study site then obtained ethical and governance approvals according to the local regulations in place [2].

### Intensive care unit and patient selection

Of the 333-participating centers of the Eurobact-2 study, we included only the centers that recruited HABSIs both in patients with and without cirrhosis for this analysis. Patients aged ≥ 18 years with a first episode of HABSI treated in the ICU were prospectively included. A HABSI was defined as a positive blood culture collected at least 48 h after hospital admission. Patients whose blood cultures were collected in the ICU (i.e., HABSI acquired in the ICU) and patients transferred to the ICU for treatment of HABSI were included. Only the first episode of HABSI was included. The presence of cirrhosis was determined based on the presence of mild to severe cirrhosis as indicated in the Charlson Comorbidity Index [22].

Blood cultures with possible skin contaminants (e.g., coagulase-negative staphylococci, *Corynebacterium* species) were carefully reviewed and included only if at least two blood cultures with the same antimicrobial susceptibility pattern were observed or if there was strong clinical suspicions that the blood culture was not a contaminant [2, 20]. Community-acquired bloodstream infections were excluded.

### Data collection

A center form was collected which described the ICU types and functioning. For each patient, data on ICU admission and on the day of the HABSI were collected. Further information on definitions is illustrated in the electronic supplementary material (ESM). Patients were
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*.

## Introduction

Hospital-acquired bloodstream infections (HABSIs) are frequent in the intensive care unit (ICU) and are associated with a high mortality [1, 2]. Cirrhotic patients are vulnerable and susceptible to hospital-acquired infections, which can affect as many as 43–59% of patients in the ICU [3–7]. Bloodstream infections have been shown to be ten times more frequent in cirrhotic patients and are associated with poor outcomes including acute on chronic liver failure, acute kidney injury, encephalopathy and mortality [3–12]. The majority of infecting bacteria found in patients with cirrhosis are Gram-negative; however, there has been an increase in the prevalence of Gram-positive bacteria with concerns for enterococcal infection [10, 13]. Treatment options in patients with liver disease are challenging for several reasons. First, the pharmacokinetics of antibiotics change with liver disease due to several physiological abnormalities such as hypoalbuminemia, altered liver and renal functions [8, 14]. Second, previous studies have shown a possible association between cirrhosis, colonization and infection by antimicrobial-resistant bacteria as well as higher rates of enterococcal infections [7, 10, 11, 15, 16]. Guidelines for empirical treatment of hospital-acquired infections in cirrhotic patients vary considerably across countries, with third generation cephalosporins, piperacillin-tazobactam or carbapenem being recommended according to local antibiotic resistance data [17, 18]. The 2018 European association for the study of the Liver (EASL) guidelines suggest considering Gram-positive coverage in cases of hospital-acquired infections [17, 18]. The question arises whether extended coverage for Gram-positive and resistant Gram-negative bacteria should be recommended as a first-line treatment in the critically ill cirrhotic patients.

Epidemiological knowledge about the microorganisms responsible for HABSI in cirrhotic patients, their sources and the patient's outcome in the ICU are scarce and no large comparison of the characteristics of these patients with a non-cirrhotic group has previously been performed [4, 8–11, 19]. The objectives of this study were to describe the differences in the epidemiology of HABSI, with particular attention to *E. faecium* infections, between cirrhotic and non-cirrhotic patients in terms of patients' characteristics, source of infection, microorganism distribution and mortality using a large multicontinental database.

## Methods

### Setting

The Eurobact-2 study was a prospective observational international cohort study conducted between August 2019 and June 2021 [2, 20].

A total of 333 centers participated in the study which was registered in ClinicalTrials.org (NCT03937245). The study was reported in accordance with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines [21].

Details regarding the methodology can be found in the previously reported Eurobact-2 study [2]. The study was approved by the ethics Committee of the Royal Brisbane & Women's Hospital Human Research (LNR/2019/QRBW/48,376). Each study site then obtained ethical and governance approvals according to the local regulations in place [2].

### Intensive care unit and patient selection

Of the 333-participating centers of the Eurobact-2 study, we included only the centers that recruited HABSIs both in patients with and without cirrhosis for this analysis. Patients aged ≥ 18 years with a first episode of HABSI treated in the ICU were prospectively included. A HABSI was defined as a positive blood culture collected at least 48 h after hospital admission. Patients whose blood cultures were collected in the ICU (i.e., HABSI acquired in the ICU) and patients transferred to the ICU for treatment of HABSI were included. Only the first episode of HABSI was included. The presence of cirrhosis was determined based on the presence of mild to severe cirrhosis as indicated in the Charlson Comorbidity Index [22].

Blood cultures with possible skin contaminants (e.g., coagulase-negative staphylococci, *Corynebacterium* species) were carefully reviewed and included only if at least two blood cultures with the same antimicrobial susceptibility pattern were observed or if there was strong clinical suspicions that the blood culture was not a contaminant [2, 20]. Community-acquired bloodstream infections were excluded.

### Data collection

A center form was collected which described the ICU types and functioning. For each patient, data on ICU admission and on the day of the HABSI were collected. Further information on definitions is illustrated in the electronic supplementary material (ESM). Patients were
followed for up to 28 days or until hospital discharge, or death.

## Statistical analysis

First, a descriptive analysis of patients' characteristics on admission according to the presence of cirrhosis was performed. Continuous variables were presented as median with interquartile range (IQR) and categorical variables as number of patients (n) and percentage (%). Chi-square or Fisher tests were used to detect differences in categorical variables as appropriate and Wilcoxon rank sum test in continuous variables. Source of infection and microorganisms' distribution were described in the same way.

Second, a descriptive analysis of the distribution of HABSI microorganisms according to the presence of cirrhosis was done. A multivariable mixed logistic regression was performed to investigate the association between *E. faecium* and cirrhosis with an adjustment for well-known risk factors for *E. faecium* infections (i.e., reason for ICU admission, source of infection, acquisition of the BSI in the ICU, use of antibiotics in the previous 7 days and delay between hospital admission and time of the BSI) [23, 24]. A random effect for the variable center was included. Results of the mixed logistic regression are expressed as odds ratios (OR).

Third, we investigated the association between cirrhosis and 28-day mortality using a graphical representation with Kaplan-Meier curves (with log-rank test). We analyzed the whole population and specifically the subgroup of patient with an *E. faecium* HABSI. The proportional hazard assumption was graphically assessed. Finally, we investigated the association between cirrhosis and mortality with a multivariable frailty Cox model with a random effect for center and adjusted for previously identified mortality risk factors (i.e., difficult-to-treat gram negative bacteria, absence of the consultation by a clinical pharmacist, source control, SAPS II on ICU admission) [2]. Moreover, a further adjustment to COVID-19 status was added since HABSI critically ill patients infected with COVID-19 showed higher mortality [20]. Results of the Cox regression analysis are expressed as hazard ratios (HR). Due to the very low number of missing data, a complete case analysis was performed.

Two-tailed *p*-values ≤ 0.05 were considered statistically significant. All statistical analyses are conducted using STATA version 16.1 (Stata Corp., College Station, TX, USA, 2007) and R (Version 3.5.3).

## Results

### Centers

Among the 333 centers recruited in the Eurobact-2 study, 232 centers were excluded as they did not include cirrhotic patients (Supplementary Figs. 1 and 2). Among the included centers, 75 were mixed ICUs (medical and

surgical), 16 were medical ICUs and 9 were surgical ICUs. A mean of 1.6 (SD 0.9) cirrhotic patients per center were recruited. In the 101 selected centers 1059 patients were included, 899 of them were non-cirrhotic patients and 160 were cirrhotic. In those patients 1196 microorganisms were identified. Further details regarding centers are shown in the Supplementary Table 1.

## Patients' characteristics

Patients characteristics on ICU admission and their outcomes according to the presence of cirrhosis are presented in Table 1. Patients median age was 64 years (IQR 53–73) and 62.5% (662/1059) were men. The primary causes for ICU admissions were septic shock (23.9%, 253/1059) and respiratory failure (21.2%, 225/1059). Cirrhotic patients were younger with a median age of 60 years (IQR 50.5–67) compared to 65 years (IQR 54–73, *p*<0.01) for non-cirrhotic patients. Their comorbidities differed significantly with cirrhotic patients presenting more often with renal disease (21.3% (34/160) vs. 16% (144/899)) and non-cirrhotic with neurological comorbidities (8.1% (13/160) vs. 14.7% (132/899)), diabetes (21.9% (35/160) vs. 27% (243/899)) and malignancy (20% (32/160) vs. 26.3% (236/899), *p*<0.01). On ICU admission, cirrhotic patients were more frequently admitted for an abdominal disease (15% (24/160) vs. 3.3% (30/899)) and for sepsis (32.5% (52/160) vs. 22.4% (201/899)) compared to non-cirrhotic patients (*p*<0.01). The 28-day mortality was higher in cirrhotic patients (45% (72/160) vs. 36.4% (327/899), *p*=0.04).

## Distribution of microorganisms, antimicrobial resistance and antibiotics used before HABSI between cirrhotic and non-cirrhotic patients

Of the 1196 microorganisms identified, 42.3% (77/182) of HABSI in cirrhotic patients were Gram-positive bacteria compared to 33.2% (337/1014) in non-cirrhotic patients (*p*=0.02) (Supplementary Table 2). Fig. 1 describes the distribution of microorganisms between cirrhotic and non-cirrhotic patients. *E. faecium* HABSI was found more often in cirrhotic patients (11.5% (21/182) vs. 4.5% (55/1014), *p*<0.01). HABSI in cirrhotic patients were most frequently caused by *Klebsiella* spp (16.5% (30/182)), coagulase-negative Staphylococci (13.7% (25/182)) and *Enterococcus faecium* (11.5% (21/182)). HABSI in non-cirrhotic patients were more commonly caused by *Klebsiella* spp (15.3% (155/1014)), *Acinetobacter* spp (10% (101/1014)) and coagulase-negative Staphylococci (9.9% (100/1014)). No difference regarding antibiotic resistance and antibiotic exposure prior to HABSI was highlighted between the two groups (Supplementary Tables 3 and 4.). Interestingly, proportions of *Klebsiella* spp and *E. coli* resistant to third generation
followed for up to 28 days or until hospital discharge, or death.

## Statistical analysis

First, a descriptive analysis of patients' characteristics on admission according to the presence of cirrhosis was performed. Continuous variables were presented as median with interquartile range (IQR) and categorical variables as number of patients (n) and percentage (%). Chi-square or Fisher tests were used to detect differences in categorical variables as appropriate and Wilcoxon rank sum test in continuous variables. Source of infection and microorganisms' distribution were described in the same way.

Second, a descriptive analysis of the distribution of HABSI microorganisms according to the presence of cirrhosis was done. A multivariable mixed logistic regression was performed to investigate the association between *E. faecium* and cirrhosis with an adjustment for well-known risk factors for *E. faecium* infections (i.e., reason for ICU admission, source of infection, acquisition of the BSI in the ICU, use of antibiotics in the previous 7 days and delay between hospital admission and time of the BSI) [23, 24]. A random effect for the variable center was included. Results of the mixed logistic regression are expressed as odds ratios (OR).

Third, we investigated the association between cirrhosis and 28-day mortality using a graphical representation with Kaplan-Meier curves (with log-rank test). We analyzed the whole population and specifically the subgroup of patient with an *E. faecium* HABSI. The proportional hazard assumption was graphically assessed. Finally, we investigated the association between cirrhosis and mortality with a multivariable frailty Cox model with a random effect for center and adjusted for previously identified mortality risk factors (i.e., difficult-to-treat gram negative bacteria, absence of the consultation by a clinical pharmacist, source control, SAPS II on ICU admission) [2]. Moreover, a further adjustment to COVID-19 status was added since HABSI critically ill patients infected with COVID-19 showed higher mortality [20]. Results of the Cox regression analysis are expressed as hazard ratios (HR). Due to the very low number of missing data, a complete case analysis was performed.

Two-tailed *p*-values ≤ 0.05 were considered statistically significant. All statistical analyses are conducted using STATA version 16.1 (Stata Corp., College Station, TX, USA, 2007) and R (Version 3.5.3).

## Results

### Centers

Among the 333 centers recruited in the Eurobact-2 study, 232 centers were excluded as they did not include cirrhotic patients (Supplementary Figs. 1 and 2). Among the included centers, 75 were mixed ICUs (medical and

surgical), 16 were medical ICUs and 9 were surgical ICUs. A mean of 1.6 (SD 0.9) cirrhotic patients per center were recruited. In the 101 selected centers 1059 patients were included, 899 of them were non-cirrhotic patients and 160 were cirrhotic. In those patients 1196 microorganisms were identified. Further details regarding centers are shown in the Supplementary Table 1.

## Patients' characteristics

Patients characteristics on ICU admission and their outcomes according to the presence of cirrhosis are presented in Table 1. Patients median age was 64 years (IQR 53–73) and 62.5% (662/1059) were men. The primary causes for ICU admissions were septic shock (23.9%, 253/1059) and respiratory failure (21.2%, 225/1059). Cirrhotic patients were younger with a median age of 60 years (IQR 50.5–67) compared to 65 years (IQR 54–73, *p*<0.01) for non-cirrhotic patients. Their comorbidities differed significantly with cirrhotic patients presenting more often with renal disease (21.3% (34/160) vs. 16% (144/899)) and non-cirrhotic with neurological comorbidities (8.1% (13/160) vs. 14.7% (132/899)), diabetes (21.9% (35/160) vs. 27% (243/899)) and malignancy (20% (32/160) vs. 26.3% (236/899), *p*<0.01). On ICU admission, cirrhotic patients were more frequently admitted for an abdominal disease (15% (24/160) vs. 3.3% (30/899)) and for sepsis (32.5% (52/160) vs. 22.4% (201/899)) compared to non-cirrhotic patients (*p*<0.01). The 28-day mortality was higher in cirrhotic patients (45% (72/160) vs. 36.4% (327/899), *p*=0.04).

## Distribution of microorganisms, antimicrobial resistance and antibiotics used before HABSI between cirrhotic and non-cirrhotic patients

Of the 1196 microorganisms identified, 42.3% (77/182) of HABSI in cirrhotic patients were Gram-positive bacteria compared to 33.2% (337/1014) in non-cirrhotic patients (*p*=0.02) (Supplementary Table 2). Fig. 1 describes the distribution of microorganisms between cirrhotic and non-cirrhotic patients. *E. faecium* HABSI was found more often in cirrhotic patients (11.5% (21/182) vs. 4.5% (55/1014), *p*<0.01). HABSI in cirrhotic patients were most frequently caused by *Klebsiella* spp (16.5% (30/182)), coagulase-negative Staphylococci (13.7% (25/182)) and *Enterococcus faecium* (11.5% (21/182)). HABSI in non-cirrhotic patients were more commonly caused by *Klebsiella* spp (15.3% (155/1014)), *Acinetobacter* spp (10% (101/1014)) and coagulase-negative Staphylococci (9.9% (100/1014)). No difference regarding antibiotic resistance and antibiotic exposure prior to HABSI was highlighted between the two groups (Supplementary Tables 3 and 4.). Interestingly, proportions of *Klebsiella* spp and *E. coli* resistant to third generation
<table><caption>**Table 1** Patients' characteristics on admission and outcomes</caption><thead><tr><th>N = 1059</th><th>Non-cirrhotic patients n = 899</th><th>Cirrhotic patients n = 160</th><th>p value</th></tr></thead><tbody><tr><td>Age (years), median (IQR)</td><td>65 (54–73)</td><td>60 (50.5–67)</td><td>&lt; 0.01</td></tr><tr><td>Gender, male, n(%)</td><td>551 (61.3%)</td><td>111 (69.4%)</td><td>0.052</td></tr><tr><td>Comorbidities, n (%):</td><td></td><td></td><td></td></tr><tr><td>-Respiratory</td><td>147 (16.4%)</td><td>25 (15.6%)</td><td>&lt; 0.01</td></tr><tr><td>-Cardiovascular</td><td>205 (22.8%)</td><td>31 (19.4%)</td><td></td></tr><tr><td>-Neurological</td><td>132 (14.7%)</td><td>13 (8.1%)</td><td></td></tr><tr><td>-Diabetes</td><td>243 (27%)</td><td>35 (21.9%)</td><td></td></tr><tr><td>-Renal insufficiency</td><td>144 (16%)</td><td>34 (21.3%)</td><td></td></tr><tr><td>-Malignancy</td><td>236 (26.3%)</td><td>32 (20%)</td><td></td></tr><tr><td>ICU admission origin, n (%):</td><td></td><td></td><td></td></tr><tr><td>-other hospital</td><td>133 (14.8%)</td><td>15 (9.4%)</td><td>0.04</td></tr><tr><td>-emergency</td><td>220 (24.5%)</td><td>27 (16.9%)</td><td></td></tr><tr><td>-OR</td><td>111 (12.4%)</td><td>23 (14.4%)</td><td></td></tr><tr><td>-hospital ward</td><td>399 (44.4%)</td><td>88 (55%)</td><td></td></tr><tr><td>-Intermediate care unit</td><td>22 (2.5%)</td><td>6 (3.4%)</td><td></td></tr><tr><td>-other</td><td>14 (1.6%)</td><td>1 (0.6%)</td><td></td></tr><tr><td>Type of admission, n (%):</td><td></td><td></td><td></td></tr><tr><td>-Medical</td><td>671 (74.6%)</td><td>121 (75.6%)</td><td>0.9</td></tr><tr><td>-Surgical elective</td><td>67 (7.5%)</td><td>10 (6.3%)</td><td></td></tr><tr><td>-Surgical emergency</td><td>161 (17.9%)</td><td>29 (18.1%)</td><td></td></tr><tr><td>Time between hospital and ICU admission (days), median (IQR)</td><td>4 (1–13)</td><td>5 (2–17)</td><td>0.4</td></tr><tr><td>Diagnosis on ICU admission, n (%):</td><td></td><td></td><td></td></tr><tr><td>-Cardiovascular disease</td><td>86 (9.6%)</td><td>10 (6.3%)</td><td>&lt; 0.01</td></tr><tr><td>-Respiratory disease</td><td>200 (22.3%)</td><td>25 (15.6%)</td><td></td></tr><tr><td>-Neurological disease</td><td>95 (10.6%)</td><td>14 (8.8%)</td><td></td></tr><tr><td>-Abdominal disease</td><td>30 (3.3%)</td><td>24 (15%)</td><td></td></tr><tr><td>-Renal failure</td><td>19 (2.1%)</td><td>2 (1.3%)</td><td></td></tr><tr><td>-Sepsis</td><td>201 (22.4%)</td><td>52 (32.5%)</td><td></td></tr><tr><td>-Post-surgery</td><td>102 (11.4%)</td><td>15 (9.4%)</td><td></td></tr><tr><td>-Others *</td><td>52 (5.8%)</td><td>8 (5%)</td><td></td></tr><tr><td>-COVID-19</td><td>114 (12.7%)</td><td>10 (6.3%)</td><td></td></tr><tr><td>SAPS II on ICU admission, median (IQR)</td><td>46 (37–58)</td><td>48 (36.5–61)</td><td>0.1</td></tr><tr><td>Lactate (mmol/L) on ICU admission, median (IQR)</td><td>2.2 (1.4–3.9)</td><td>3 (1.7–5.1)</td><td>&lt; 0.01</td></tr><tr><td>Bilirubin (µmol/L) on ICU admission, median (IQR)</td><td>1.8 (0.7–10.1)</td><td>7.5 (1.5–35)</td><td>&lt; 0.01</td></tr><tr><td>WBC (x10⁹/L) on ICU admission, median (IQR)</td><td>14.3 (9.4–22.4)</td><td>14.5 (8.9–22.5)</td><td>0.7</td></tr><tr><td>CRP (mg/l) on ICU admission, median (IQR)</td><td>117.6 (33.5–215)</td><td>70 (23.2–155.6)</td><td>&lt; 0.01</td></tr><tr><td>Need for renal replacement therapy during ICU stay, n (%)</td><td>126 (14%)</td><td>27 (16.9%)</td><td>0.3</td></tr><tr><td>Ventilation needs during ICU stay, n(%):</td><td></td><td></td><td></td></tr><tr><td>-Mechanical ventilation</td><td>546 (60.8%)</td><td>92 (57.5%)</td><td>0.2</td></tr><tr><td>-Non-invasive ventilation</td><td>75 (8.4%)</td><td>21 (13.1%)</td><td></td></tr><tr><td>-High flow</td><td>75 (8.4%)</td><td>10 (6.3%)</td><td></td></tr><tr><td>-low flow or nothing</td><td>201 (22.4%)</td><td>37 (23.1%)</td><td></td></tr><tr><td>Known MDRO before admission, n(%)</td><td>173 (19.3%)</td><td>28 (17.5%)</td><td>0.6</td></tr><tr><td>Antibiotics in the previous 7 days, n(%)</td><td>661 (73.5%)</td><td>119 (74.4%)</td><td>0.8</td></tr><tr><td>Days under mechanical ventilation, median (IQR)</td><td>6 (1–18)</td><td>6.5 (1–13)</td><td>0.4</td></tr><tr><td>ICU length of stay (days), median (IQR)</td><td>16 (7–27)</td><td>13.5 (6–30)</td><td>0.5</td></tr><tr><td>Death at day 28, n(%)</td><td>327 (36.4%)</td><td>72 (45%)</td><td>0.04</td></tr></tbody></table>

Results reported as n (%) for categorical variables and median (IQR) for continuous variables

ICU intensive care unit; OR operating room; WBC white blood cells; CRP C-reactive protein; MDRO multi-drug resistant organisms

*: multiple trauma with no traumatic brain injury, metabolic disturbances, drug overdose, diabetic ketoacidosis, anaphylaxis

cephalosporins were 50% in cirrhotic patients and 55.8% in non-cirrhotic patients (p=0.5).

## Characteristics of HABSI and sources of infection

HABSIs were more frequently acquired in the ICU than on the ward in both groups (Table 2). Compared

to non-cirrhotic patients, cirrhotic patients developed HABSI on the ward more often (31.9% (51/160) vs. 23.9% (215/899), p=0.03). The most common source of HABSI in cirrhotic patient was abdominal (35.6% (57/160)) whereas it was pulmonary (18.9% (207/899))
<table><caption>**Table 1** Patients' characteristics on admission and outcomes</caption><thead><tr><th>N = 1059</th><th>Non-cirrhotic patients n = 899</th><th>Cirrhotic patients n = 160</th><th>p value</th></tr></thead><tbody><tr><td>Age (years), median (IQR)</td><td>65 (54–73)</td><td>60 (50.5–67)</td><td>&lt; 0.01</td></tr><tr><td>Gender, male, n(%)</td><td>551 (61.3%)</td><td>111 (69.4%)</td><td>0.052</td></tr><tr><td>Comorbidities, n (%):</td><td></td><td></td><td></td></tr><tr><td>-Respiratory</td><td>147 (16.4%)</td><td>25 (15.6%)</td><td>&lt; 0.01</td></tr><tr><td>-Cardiovascular</td><td>205 (22.8%)</td><td>31 (19.4%)</td><td></td></tr><tr><td>-Neurological</td><td>132 (14.7%)</td><td>13 (8.1%)</td><td></td></tr><tr><td>-Diabetes</td><td>243 (27%)</td><td>35 (21.9%)</td><td></td></tr><tr><td>-Renal insufficiency</td><td>144 (16%)</td><td>34 (21.3%)</td><td></td></tr><tr><td>-Malignancy</td><td>236 (26.3%)</td><td>32 (20%)</td><td></td></tr><tr><td>ICU admission origin, n (%):</td><td></td><td></td><td></td></tr><tr><td>-other hospital</td><td>133 (14.8%)</td><td>15 (9.4%)</td><td>0.04</td></tr><tr><td>-emergency</td><td>220 (24.5%)</td><td>27 (16.9%)</td><td></td></tr><tr><td>-OR</td><td>111 (12.4%)</td><td>23 (14.4%)</td><td></td></tr><tr><td>-hospital ward</td><td>399 (44.4%)</td><td>88 (55%)</td><td></td></tr><tr><td>-Intermediate care unit</td><td>22 (2.5%)</td><td>6 (3.4%)</td><td></td></tr><tr><td>-other</td><td>14 (1.6%)</td><td>1 (0.6%)</td><td></td></tr><tr><td>Type of admission, n (%):</td><td></td><td></td><td></td></tr><tr><td>-Medical</td><td>671 (74.6%)</td><td>121 (75.6%)</td><td>0.9</td></tr><tr><td>-Surgical elective</td><td>67 (7.5%)</td><td>10 (6.3%)</td><td></td></tr><tr><td>-Surgical emergency</td><td>161 (17.9%)</td><td>29 (18.1%)</td><td></td></tr><tr><td>Time between hospital and ICU admission (days), median (IQR)</td><td>4 (1–13)</td><td>5 (2–17)</td><td>0.4</td></tr><tr><td>Diagnosis on ICU admission, n (%):</td><td></td><td></td><td></td></tr><tr><td>-Cardiovascular disease</td><td>86 (9.6%)</td><td>10 (6.3%)</td><td>&lt; 0.01</td></tr><tr><td>-Respiratory disease</td><td>200 (22.3%)</td><td>25 (15.6%)</td><td></td></tr><tr><td>-Neurological disease</td><td>95 (10.6%)</td><td>14 (8.8%)</td><td></td></tr><tr><td>-Abdominal disease</td><td>30 (3.3%)</td><td>24 (15%)</td><td></td></tr><tr><td>-Renal failure</td><td>19 (2.1%)</td><td>2 (1.3%)</td><td></td></tr><tr><td>-Sepsis</td><td>201 (22.4%)</td><td>52 (32.5%)</td><td></td></tr><tr><td>-Post-surgery</td><td>102 (11.4%)</td><td>15 (9.4%)</td><td></td></tr><tr><td>-Others *</td><td>52 (5.8%)</td><td>8 (5%)</td><td></td></tr><tr><td>-COVID-19</td><td>114 (12.7%)</td><td>10 (6.3%)</td><td></td></tr><tr><td>SAPS II on ICU admission, median (IQR)</td><td>46 (37–58)</td><td>48 (36.5–61)</td><td>0.1</td></tr><tr><td>Lactate (mmol/L) on ICU admission, median (IQR)</td><td>2.2 (1.4–3.9)</td><td>3 (1.7–5.1)</td><td>&lt; 0.01</td></tr><tr><td>Bilirubin (µmol/L) on ICU admission, median (IQR)</td><td>1.8 (0.7–10.1)</td><td>7.5 (1.5–35)</td><td>&lt; 0.01</td></tr><tr><td>WBC (x10⁹/L) on ICU admission, median (IQR)</td><td>14.3 (9.4–22.4)</td><td>14.5 (8.9–22.5)</td><td>0.7</td></tr><tr><td>CRP (mg/l) on ICU admission, median (IQR)</td><td>117.6 (33.5–215)</td><td>70 (23.2–155.6)</td><td>&lt; 0.01</td></tr><tr><td>Need for renal replacement therapy during ICU stay, n (%)</td><td>126 (14%)</td><td>27 (16.9%)</td><td>0.3</td></tr><tr><td>Ventilation needs during ICU stay, n(%):</td><td></td><td></td><td></td></tr><tr><td>-Mechanical ventilation</td><td>546 (60.8%)</td><td>92 (57.5%)</td><td>0.2</td></tr><tr><td>-Non-invasive ventilation</td><td>75 (8.4%)</td><td>21 (13.1%)</td><td></td></tr><tr><td>-High flow</td><td>75 (8.4%)</td><td>10 (6.3%)</td><td></td></tr><tr><td>-low flow or nothing</td><td>201 (22.4%)</td><td>37 (23.1%)</td><td></td></tr><tr><td>Known MDRO before admission, n(%)</td><td>173 (19.3%)</td><td>28 (17.5%)</td><td>0.6</td></tr><tr><td>Antibiotics in the previous 7 days, n(%)</td><td>661 (73.5%)</td><td>119 (74.4%)</td><td>0.8</td></tr><tr><td>Days under mechanical ventilation, median (IQR)</td><td>6 (1–18)</td><td>6.5 (1–13)</td><td>0.4</td></tr><tr><td>ICU length of stay (days), median (IQR)</td><td>16 (7–27)</td><td>13.5 (6–30)</td><td>0.5</td></tr><tr><td>Death at day 28, n(%)</td><td>327 (36.4%)</td><td>72 (45%)</td><td>0.04</td></tr></tbody></table>

Results reported as n (%) for categorical variables and median (IQR) for continuous variables

ICU intensive care unit; OR operating room; WBC white blood cells; CRP C-reactive protein; MDRO multi-drug resistant organisms

*: multiple trauma with no traumatic brain injury, metabolic disturbances, drug overdose, diabetic ketoacidosis, anaphylaxis

cephalosporins were 50% in cirrhotic patients and 55.8% in non-cirrhotic patients (p=0.5).

## Characteristics of HABSI and sources of infection

HABSIs were more frequently acquired in the ICU than on the ward in both groups (Table 2). Compared

to non-cirrhotic patients, cirrhotic patients developed HABSI on the ward more often (31.9% (51/160) vs. 23.9% (215/899), p=0.03). The most common source of HABSI in cirrhotic patient was abdominal (35.6% (57/160)) whereas it was pulmonary (18.9% (207/899))
<figure><img src="image_5.png" /><figcaption>**Fig. 1** The distribution of microorganisms between cirrhotic and non-cirrhotic patients was compared, with the results reported as the number of each microorganism in the two different patient groups. The Fisher's exact test was used for the comparison, revealing a significant difference in microorganism distribution between cirrhotic and non-cirrhotic patients (p = 0.01)</figcaption></figure>

<table><caption>**Table 2** Characteristics of HABSI and sources of infection</caption><thead><tr><th>N = 1059</th><th>Non-cirrhotic patients<br>n = 899</th><th>Cirrhotic patients<br>n = 160</th><th>p value</th></tr></thead><tbody><tr><td>Time to HABSI (days), median (IQR)</td><td>14 (8-26)</td><td>15 (8-25)</td><td>0.6</td></tr><tr><td>Site of acquisition, n(%)</td><td>215 (23.9%)</td><td>51 (31.9%)</td><td rowspan="2">0.03</td></tr><tr><td>-Ward</td><td>684 (75.1%)</td><td>109 (68.1%)</td></tr><tr><td>-ICU</td><td></td><td></td><td></td></tr><tr><td>Supposed source of the HABSI, n (%)</td><td>110 (12.2%)</td><td>19 (11.9%)</td><td rowspan="7">&lt;0.01</td></tr><tr><td>-primary</td><td>170 (18.9%)</td><td>24 (15%)</td></tr><tr><td>-catheter related</td><td>207 (23%)</td><td>23 (14.4%)</td></tr><tr><td>-pulmonary</td><td>169 (18.8%)</td><td>57 (35.6%)</td></tr><tr><td>-abdominal</td><td>105 (11.7%)</td><td>16 (10%)</td></tr><tr><td>-urinary tract</td><td>63 (7%)</td><td>10 (6.3%)</td></tr><tr><td>-cutaneous or soft tissue -others*</td><td>75 (8.3%)</td><td>11 (6.9%)</td></tr><tr><td>Source control, n (%)</td><td>381 (42.4%)</td><td>75 (46.9%)</td><td rowspan="4">0.6</td></tr><tr><td>-not required</td><td>426 (47.4%)</td><td>71 (44.4%)</td></tr><tr><td>-required and complete</td><td>92 (10.2%)</td><td>14 (8.8%)</td></tr><tr><td>-required but unsuccessful</td><td></td><td></td></tr><tr><td>Appropriate antibiotic in the first 24 h, n (%)</td><td>459 (51.1%)</td><td>78 (48.7%)</td><td>0.6</td></tr></tbody></table>

Results reported as n (%) for categorical variables and median (IQR) for continuous variables

*mediastinitis, endocarditis, joints, central nervous system

HABSI hospital-acquired bloodstream infection; ICU intensive care unit

for non-cirrhotic patients (p < 0.01). Patients' characteristics on HABSI day are illustrated in the Supplementary Table 5.

### Association between *E. faecium* and cirrhosis

Using a multivariable mixed logistic regression model and after adjustment for well-known *E. faecium* risk factors, cirrhosis was associated with a higher risk of *E. faecium* HABSI (OR 2.5, 95% CI 1.3–4.5, p < 0.01, Table 3). Description of patients with *E. faecium* HABSI is shown in the Supplementary Table 6. Importantly, 84% of *E. faecium* HABSI were acquired in the ICU.

### Association between cirrhosis and mortality

Mortality on day 28 was higher in cirrhotic patients compared to non-cirrhotic patients (p = 0.04) (Fig. 2). The proportionality assumption was respected. A multivariable frailty Cox model showed an increased risk of death in HABSI patients known for cirrhosis (HR 1.3, 95% CI 1.01–1.7, p = 0.045, Supplementary Table 7). Cirrhotic patients with *E. faecium* HABSI tended to have an even higher 28-day mortality; however, this result was non-significant.
<figure><img src="image_5.png" /><figcaption>**Fig. 1** The distribution of microorganisms between cirrhotic and non-cirrhotic patients was compared, with the results reported as the number of each microorganism in the two different patient groups. The Fisher's exact test was used for the comparison, revealing a significant difference in microorganism distribution between cirrhotic and non-cirrhotic patients (p = 0.01)</figcaption></figure>

<table><caption>**Table 2** Characteristics of HABSI and sources of infection</caption><thead><tr><th>N = 1059</th><th>Non-cirrhotic patients n = 899</th><th>Cirrhotic patients n = 160</th><th>p value</th></tr></thead><tbody><tr><td>Time to HABSI (days), median (IQR)</td><td>14 (8-26)</td><td>15 (8-25)</td><td>0.6</td></tr><tr><td>Site of acquisition, n(%)</td><td>215 (23.9%)</td><td>51 (31.9%)</td><td rowspan="2">0.03</td></tr><tr><td>-Ward</td><td>684 (75.1%)</td><td>109 (68.1%)</td></tr><tr><td>-ICU</td><td></td><td></td><td></td></tr><tr><td>Supposed source of the HABSI, n (%)</td><td>110 (12.2%)</td><td>19 (11.9%)</td><td rowspan="7">&lt;0.01</td></tr><tr><td>-primary</td><td>170 (18.9%)</td><td>24 (15%)</td></tr><tr><td>-catheter related</td><td>207 (23%)</td><td>23 (14.4%)</td></tr><tr><td>-pulmonary</td><td>169 (18.8%)</td><td>57 (35.6%)</td></tr><tr><td>-abdominal</td><td>105 (11.7%)</td><td>16 (10%)</td></tr><tr><td>-urinary tract</td><td>63 (7%)</td><td>10 (6.3%)</td></tr><tr><td>-cutaneous or soft tissue -others*</td><td>75 (8.3%)</td><td>11 (6.9%)</td></tr><tr><td>Source control, n (%)</td><td>381 (42.4%)</td><td>75 (46.9%)</td><td rowspan="4">0.6</td></tr><tr><td>-not required</td><td>426 (47.4%)</td><td>71 (44.4%)</td></tr><tr><td>-required and complete</td><td>92 (10.2%)</td><td>14 (8.8%)</td></tr><tr><td>-required but unsuccessful</td><td></td><td></td></tr><tr><td>Appropriate antibiotic in the first 24 h, n (%)</td><td>459 (51.1%)</td><td>78 (48.7%)</td><td>0.6</td></tr></tbody></table>

Results reported as n (%) for categorical variables and median (IQR) for continuous variables

for non-cirrhotic patients (p < 0.01). Patients' characteristics on HABSI day are illustrated in the Supplementary Table 5.

### Association between *E. faecium* and cirrhosis

Using a multivariable mixed logistic regression model and after adjustment for well-known *E. faecium* risk factors, cirrhosis was associated with a higher risk of *E. faecium* HABSI (OR 2.5, 95% CI 1.3–4.5, p < 0.01, Table 3). Description of patients with *E. faecium* HABSI is shown in the Supplementary Table 6. Importantly, 84% of *E. faecium* HABSI were acquired in the ICU.

### Association between cirrhosis and mortality

Mortality on day 28 was higher in cirrhotic patients compared to non-cirrhotic patients (p = 0.04) (Fig. 2). The proportionality assumption was respected. A multivariable frailty Cox model showed an increased risk of death in HABSI patients known for cirrhosis (HR 1.3, 95% CI 1.01–1.7, p = 0.045, Supplementary Table 7). Cirrhotic patients with *E. faecium* HABSI tended to have an even higher 28-day mortality; however, this result was non-significant.

<footnote>*mediastinitis, endocarditis, joints, central nervous system</footnote>

<footnote>HABSI hospital-acquired bloodstream infection; ICU intensive care unit</footnote>
<table><caption>**Table 3** Multivariable logistic mixed model for the association between *E. faecium* and cirrhosis</caption><thead><tr><th>n = 1059</th><th>E. faecium BSI, Odds ratio (95% CI)</th><th>p value</th></tr></thead><tbody><tr><td><strong>Cirrhosis</strong></td><td>2.5 (1.3–4.5)</td><td>&lt;0.01</td></tr><tr><td>Reason for ICU admission:</td><td></td><td></td></tr><tr><td>-Cardio-vascular disease</td><td>Ref.</td><td></td></tr><tr><td>-Cardio-vascular disease</td><td>1.5 (0.5–4.4)</td><td>0.4</td></tr><tr><td>-Neurological disease</td><td>0.3 (0.06–1.8)</td><td>0.2</td></tr><tr><td>-Abdominal disease</td><td>1.5 (0.5–5.2)</td><td>0.5</td></tr><tr><td>-Post-surgical treatment</td><td>0.9 (0.3–3.1)</td><td>0.9</td></tr><tr><td>-Renal failure</td><td>1.2 (0.1–11)</td><td>0.9</td></tr><tr><td>-Septic Shock</td><td>0.7 (0.2–2)</td><td>0.5</td></tr><tr><td>-COVID-19</td><td>3.2 (1.1–10)</td><td>0.04</td></tr><tr><td>-other*</td><td>0.7 (0.1–3.1)</td><td>0.6</td></tr><tr><td>Source of infection:</td><td></td><td></td></tr><tr><td>-Primary</td><td>Ref.</td><td></td></tr><tr><td>-Intravascular catheter related</td><td>0.6 (0.3–1.5)</td><td>0.3</td></tr><tr><td>-Pulmonary</td><td>0.2 (0.1–0.6)</td><td>&lt;0.01</td></tr><tr><td>-Abdominal</td><td>0.4 (0.1–1.3)</td><td>0.5</td></tr><tr><td>-Urinary</td><td>0.4 (0.1–1.3)</td><td>0.1</td></tr><tr><td>-Skin</td><td>0.9 (0.3–3)</td><td>0.9</td></tr><tr><td>-Other†</td><td>0.6 (0.2–2)</td><td>0.4</td></tr><tr><td>BSI acquired before ICU admission</td><td>0.6 (0.3–1.3)</td><td>0.2</td></tr><tr><td>Antibiotics in the last 7 days</td><td>1.9 (0.9–3.9)</td><td>0.056</td></tr><tr><td>Delay (days) between hospital admission and BSI</td><td>0.9 (0.9–1.1)</td><td>0.7</td></tr></tbody></table>

Results are expressed as odds ratios and 95% confidence interval (95% CI). A random effect for center was included

HABSI hospital-acquired bloodstream infection

*: multiple trauma with no traumatic brain injury, metabolic disturbances, drug overdose, diabetic ketoacidosis, anaphylaxis

†: mediastinitis, endocarditis, joints, central nervous system

Discussion

In this analysis of a prospective multicontinental cohort of patients with HABSI, we found that patients with liver cirrhosis had higher mortality than those without cirrhosis. HABSI in cirrhotic patients were more frequently due to Gram-positive bacteria, especially *E. faecium*, than in non-cirrhotic patients. No difference regarding antimicrobial resistance was observed between the two groups.

Previous studies showed similar rates of Gram-positive (26.3–49%) and Gram-negative (48–57.2%) HABSI in cirrhotic patients [10, 15]. These studies found that 2 to 9% of HABSI were due to *E. faecium*. The differences and limitations of these previous studies are that (1) they were monocentric or included only a limited number of centers, (2) they did not focus on ICU patients and, (3) they did not perform a comparison between cirrhotic and non-cirrhotic patients. Using a large multicontinental database that prospectively included patients, we observed that the rate of Gram-positive bacteremia was higher in critically ill cirrhotic patients than in non-cirrhotic patients, with *E. faecium* much more prevalent

among cirrhotic patients. There are several hypotheses for this finding. First, the source of the bacteremia in cirrhotic patients was more often abdominal and enterococci are known to colonize the intestinal tract. Second, cirrhotic patients are exposed to repeated prophylactic and therapeutic antibiotic treatments. Indeed, these patients frequently receive antibiotics because they are more prone to infections and especially to spontaneous bacterial peritonitis [6]. Interestingly, we did not observe differences in antibiotics administered 7 days before HABSI. However, since we had no access to data on antibiotic therapies in the months before HABSI, it is conceivable that cirrhotic patients were more frequently exposed to antimicrobial substances which might have impacted the epidemiology of their HABSI. Lastly, our population included only HABSI and this setting is characterized by higher prevalence of *E. faecium*, whereas *E. faecalis* tends to occur more frequently in the community-acquired setting [25].

Our results have clinical implications. The high rate of *E. faecium* HABSI found in cirrhotic patients may challenge empirical antibiotic therapies that should be proposed in this particular setting. A study showed that clinicians felt that in cases of severe sepsis, 90% of all probable microorganisms should be covered by the empirical antibiotics chosen [26]. As *E. faecium* accounts for more than 10% of HABSI observed in these critically ill cirrhotic patients, empiric coverage with glycopeptides, daptomycin or oxazolidinones should be considered. This coverage seems particularly important if the suspected source is abdominal: a recent multicentric study found that intra-abdominal infections in critically ill patients growing *Enterococcus* were associated with a higher mortality when there was no empirical coverage of *E. faecium* [27].

Regarding other specific resistances to antibiotics in the context of cirrhosis, some previous studies have reported higher rates of drug-resistant organisms such as extended spectrum beta-lactamase (ESBL) or methicillin-resistant *Staphylococcus aureus* (MRSA), depending highly on the local ecology [7, 10, 11]. However, our study did not show any difference in antimicrobial resistance between patients with and without cirrhosis. Therefore, cirrhosis per se does not seem to influence the risk of resistance relative to other patients in the ICU with HABSI, but it mostly impacts the distribution of strains causing HABSI. Interestingly, the proportion of *Klebsiella* spp and *E. coli* spp resistant to third-generation cephalosporins represented almost 50% of all HABSI in the Eurobact-2 cohort without differences between cirrhotic and non-cirrhotic patients. This finding seems to be associated with the local ecology; therefore, no firm conclusion on empirical antibiotic therapy for Gram-negative microorganisms for cirrhotic patients can be provided.
<table><caption>**Table 3** Multivariable logistic mixed model for the association between *E. faecium* and cirrhosis</caption><thead><tr><th>n = 1059</th><th>E. faecium BSI, Odds ratio (95% CI)</th><th>p value</th></tr></thead><tbody><tr><td><strong>Cirrhosis</strong></td><td>2.5 (1.3-4.5)</td><td>&lt;0.01</td></tr><tr><td>Reason for ICU admission:</td><td></td><td></td></tr><tr><td>-Cardio-vascular disease</td><td>Ref.</td><td></td></tr><tr><td>-Cardio-vascular disease</td><td>1.5 (0.5-4.4)</td><td>0.4</td></tr><tr><td>-Neurological disease</td><td>0.3 (0.06-1.8)</td><td>0.2</td></tr><tr><td>-Abdominal disease</td><td>1.5 (0.5-5.2)</td><td>0.5</td></tr><tr><td>-Post-surgical treatment</td><td>0.9 (0.3-3.1)</td><td>0.9</td></tr><tr><td>-Renal failure</td><td>1.2 (0.1-11)</td><td>0.9</td></tr><tr><td>-Septic Shock</td><td>0.7 (0.2-2)</td><td>0.5</td></tr><tr><td>-COVID-19</td><td>3.2 (1.1-10)</td><td>0.04</td></tr><tr><td>-other*</td><td>0.7 (0.1-3.1)</td><td>0.6</td></tr><tr><td>Source of infection:</td><td></td><td></td></tr><tr><td>-Primary</td><td>Ref.</td><td></td></tr><tr><td>-Intravascular catheter related</td><td>0.6 (0.3-1.5)</td><td>0.3</td></tr><tr><td>-Pulmonary</td><td>0.2 (0.1-0.6)</td><td>&lt;0.01</td></tr><tr><td>-Abdominal</td><td>0.4 (0.1-1.3)</td><td>0.5</td></tr><tr><td>-Urinary</td><td>0.4 (0.1-1.3)</td><td>0.1</td></tr><tr><td>-Skin</td><td>0.9 (0.3-3)</td><td>0.9</td></tr><tr><td>-Other†</td><td>0.6 (0.2-2)</td><td>0.4</td></tr><tr><td>BSI acquired before ICU admission</td><td>0.6 (0.3-1.3)</td><td>0.2</td></tr><tr><td>Antibiotics in the last 7 days</td><td>1.9 (0.9-3.9)</td><td>0.056</td></tr><tr><td>Delay (days) between hospital admission and BSI</td><td>0.9 (0.9-1.1)</td><td>0.7</td></tr></tbody></table>

Results are expressed as odds ratios and 95% confidence interval (95% CI). A random effect for center was included

*HABSI hospital-acquired bloodstream infection*

*: multiple trauma with no traumatic brain injury, metabolic disturbances, drug overdose, diabetic ketoacidosis, anaphylaxis

†: mediastinitis, endocarditis, joints, central nervous system

## Discussion

In this analysis of a prospective multicontinental cohort of patients with HABSI, we found that patients with liver cirrhosis had higher mortality than those without cirrhosis. HABSI in cirrhotic patients were more frequently due to Gram-positive bacteria, especially *E. faecium*, than in non-cirrhotic patients. No difference regarding antimicrobial resistance was observed between the two groups.

Previous studies showed similar rates of Gram-positive (26.3–49%) and Gram-negative (48–57.2%) HABSI in cirrhotic patients [10, 15]. These studies found that 2 to 9% of HABSI were due to *E. faecium*. The differences and limitations of these previous studies are that (1) they were monocentric or included only a limited number of centers, (2) they did not focus on ICU patients and, (3) they did not perform a comparison between cirrhotic and non-cirrhotic patients. Using a large multicontinental database that prospectively included patients, we observed that the rate of Gram-positive bacteremia was higher in critically ill cirrhotic patients than in non-cirrhotic patients, with *E. faecium* much more prevalent

among cirrhotic patients. There are several hypotheses for this finding. First, the source of the bacteremia in cirrhotic patients was more often abdominal and enterococci are known to colonize the intestinal tract. Second, cirrhotic patients are exposed to repeated prophylactic and therapeutic antibiotic treatments. Indeed, these patients frequently receive antibiotics because they are more prone to infections and especially to spontaneous bacterial peritonitis [6]. Interestingly, we did not observe differences in antibiotics administered 7 days before HABSI. However, since we had no access to data on antibiotic therapies in the months before HABSI, it is conceivable that cirrhotic patients were more frequently exposed to antimicrobial substances which might have impacted the epidemiology of their HABSI. Lastly, our population included only HABSI and this setting is characterized by higher prevalence of *E. faecium*, whereas *E. faecalis* tends to occur more frequently in the community-acquired setting [25].

Our results have clinical implications. The high rate of *E. faecium* HABSI found in cirrhotic patients may challenge empirical antibiotic therapies that should be proposed in this particular setting. A study showed that clinicians felt that in cases of severe sepsis, 90% of all probable microorganisms should be covered by the empirical antibiotics chosen [26]. As *E. faecium* accounts for more than 10% of HABSI observed in these critically ill cirrhotic patients, empiric coverage with glycopeptides, daptomycin or oxazolidinones should be considered. This coverage seems particularly important if the suspected source is abdominal: a recent multicentric study found that intra-abdominal infections in critically ill patients growing *Enterococcus* were associated with a higher mortality when there was no empirical coverage of *E. faecium* [27].

Regarding other specific resistances to antibiotics in the context of cirrhosis, some previous studies have reported higher rates of drug-resistant organisms such as extended spectrum beta-lactamase (ESBL) or methicillin-resistant *Staphylococcus aureus* (MRSA), depending highly on the local ecology [7, 10, 11]. However, our study did not show any difference in antimicrobial resistance between patients with and without cirrhosis. Therefore, cirrhosis per se does not seem to influence the risk of resistance relative to other patients in the ICU with HABSI, but it mostly impacts the distribution of strains causing HABSI. Interestingly, the proportion of *Klebsiella* spp and *E. coli* spp resistant to third-generation cephalosporins represented almost 50% of all HABSI in the Eurobact-2 cohort without differences between cirrhotic and non-cirrhotic patients. This finding seems to be associated with the local ecology; therefore, no firm conclusion on empirical antibiotic therapy for Gram-negative microorganisms for cirrhotic patients can be provided.
**Overall survival curve**
(N=1059)

<figure><img src="image_6.png" /></figure>

**Survival curve (E.Faecium)**
(N=75)

<figure><img src="image_7.png" /></figure>

**Fig. 2** Kaplan-Meier survival curves were used to analyze survival until Day 28 for all HABSIs and for *Enterococcus faecium* HABSI in cirrhotic and non-cirrhotic patients. Statistical analysis of the Kaplan-Meier curve (log-rank test) showed a lower probability of survival in cirrhotic patients with HABSI (*p* = 0.04) and no significant difference in cirrhotic patients with *E. faecium* HABSI compared to non-cirrhotic patients (*p* = 0.46)
**Overall survival curve**
(N=1059)

<figure><img src="image_6.png" /></figure>

**Survival curve (E.Faecium)**
(N=75)

<figure><img src="image_7.png" /><figcaption>**Fig. 2** Kaplan-Meier survival curves were used to analyze survival until Day 28 for all HABSIs and for *Enterococcus faecium* HABSI in cirrhotic and non-cirrhotic patients. Statistical analysis of the Kaplan-Meier curve (log-rank test) showed a lower probability of survival in cirrhotic patients with HABSI (*p* = 0.04) and no significant difference in cirrhotic patients with *E. faecium* HABSI compared to non-cirrhotic patients (*p* = 0.46)</figcaption></figure>
Our study revealed that there was no significant difference in the incidence of fungal HABSI between cirrhotic and non-cirrhotic patients. This finding is noteworthy as these infections are often concerning in cirrhotic patients as previous studies highlighted more invasive fungal infections in cirrhotic patients compared to non-cirrhotic patients, especially in an ICU setting [28, 29]. However, the results of our study suggest that cirrhotic patients may not be at a higher risk for fungal infections, which has important implications for clinical management strategies.

Our study highlights that critically ill cirrhotic patients with HABSI were associated with poorer outcomes, with a mortality rate reaching 45%, which was significantly higher than non-cirrhotic patients. This has already been highlighted for nosocomial infections in cirrhotic patients [30]. Active measures to prevent nosocomial infections, including HABSI, should be thoroughly applied to these vulnerable patients. This can be achieved through excellent infection prevention and control measures targeting the most important healthcare-associated infections, reducing the unnecessary use of proton pump inhibitors, avoiding the placement of intravascular and urinary catheters and limiting their duration [30, 31].

Our study has several limitations. First, ICUs in high income countries and European ICUs were overrepresented with three countries (France, UK and Turkey) recruiting 30% of patients, thus potentially limiting the generalizability of our results [2]. However, each continent was represented and included patients in our study. Second, pathogen identification and antimicrobial susceptibility testing was dependent on each center's laboratory, which limits the standardization of microbiological results [2]. Third, the causes and severity of cirrhosis could not be assessed, which could have influenced the outcome [13]. Fourth, data collection was performed by individual investigators in each ICU without on-site monitoring. This limitation was controlled by providing online checks through the electronic case report file and by monitoring data quality and coherence of the data for each case-report form [2]. Lastly, this is a secondary analysis of the Eurobact-II database, with the inherent risk of bias that such analyses may carry.

In summary, critically ill cirrhotic patients with HABSI have a higher mortality than those without cirrhosis. They present a specific microbiology, with more Gram-positive bacteria and especially more *E. faecium* bacteremia than non-cirrhotic patients. In these particular patients, empirical coverage of *E. faecium* should be considered. This should be confirmed by interventional studies specifically designed to determine the efficacy and safety of such antibiotic treatments in this high-risk population.

## Abbreviations

<table><tr><td>HABSI</td><td>Hospital-acquired bloodstream infections</td></tr><tr><td>ICU</td><td>intensive care unit</td></tr><tr><td>SAPSII</td><td>simplified acute physiology score II</td></tr><tr><td>SOFA</td><td>sequential organ failure assessment</td></tr><tr><td>OR</td><td>operating room</td></tr><tr><td>WBC</td><td>white blood cells</td></tr><tr><td>CRP</td><td>C-reactive protein</td></tr><tr><td>CVVHDF</td><td>continuous venovenous hemodiafiltration</td></tr><tr><td>SLEDD</td><td>Sustained low-efficiency daily dialysis</td></tr><tr><td>MDRO</td><td>multi-drug resistant organisms</td></tr></table>

## Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s13613-024-01299-x.

Supplementary Material 1

Supplementary Material 2

## Acknowledgements

The Eurobact 2 study group, National coordinators, scientific committee and participating intensive care units: **Middle East: Israel-National Coordinator:** Prof. Pierre Singer; **Participating ICU:** Rabin Medical Center Beilinson Hospital, General Intensive Care: Prof Pierre Singer, Dr Ilya Kagan, Dr Merav Rigler.
**Egypt:** **National Coordinator:** Dr. Adel Alsisi Cairo University Hospital (Qasr Al Ainy), Critical Care Department: Dr Adel Alsisi, Dr Amr Elhadidy, Dr Mina Barsoum.Medical Research Institute, Alexandria University, Biomedical Informatics and Medical Statistics (Icu): Dr Nermin Osman. Tanta University Hospital, Anaesthesia and Critical Care Department: Dr Tarek Mostafa. Tanta University Faculty of Medicine, Emergency Medicine and Traumatology Department: Dr Mohamed Elbahnasawy. Nasr City Health Insurance Hospital, Medical Icu: Dr Amer Aldhalia. Wingat Royal Hospital, Wingat Icu: Dr Omar Elmandouh. **Latin America: Mexico**—**National Coordinator:** Dr. Silvio A. Namendys-Silva; **Participating ICUs:** Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Division of Pulmonary, Anesthesia and Critical Care Medicine: Dr Jose G. Dominguez-Cherit, Dr Adrian Davalos-Alvarez, Dr Silvio A. Namendys-Silva. UMAE Hospital de Especialidades Antonio Fraga Mouret.
**Europe And Central Asia: Belgium**—**National Coordinator:** Dr. Liesbet De Bus; **Participating ICUs:** Ghent University Hospital, Intensive Care Unit: Dr Liesbet De Bus, Dr Jan De Waele. A.S.Z., Iz: Dr Isabelle Hollevoet. Az Nikolaas, Icu: Dr Wouter Denys. Centre Hospitalier De Jolimont, Soins Intensifs: Dr Jean-Baptiste Mesland, Dr Pierre Henin. Cliniques Universitaires Saint-Luc, UCLouvain, Soins Intensifs: Dr Xavier Wittebole. Uzbrussel, Intensieve Zorgen: Prof Elisabeth De Waele, Mrs Godelive Opdenacker. **Bosnia And Herzegovina:** **National Coordinator:** Dr. Pedja Kovacevic; **Participating ICUs:** University Clinical Centre of The Republic Of Srpska, Medical Intensive Care Unit: Dr Pedja Kovacevic, Dr Biljana Zlojutro. **France**—**National Coordinator:** Prof. Marc Leone; **Scientific Committee:** Prof. Jean-François Timsit, Prof. Etienne Ruppe, Mr. Stephane Ruckly, Prof. Philippe Montravers; Bichat Claude Bernard, Réanimation Médicale et Infectieuse: Prof Jean-François Timsit, Mme Juliette Patrier. Bichat-Claude Bernard Hospital, Ap-Hp, Anesthesiology And Critical Care Medicine Department, Dmu Parabol: Dr N.Zappela, Pr P. Montravers. Ch Annecy Genevois, Réanimation Polyvalente: Dr Etienne Escudier. Chu Lille, Hôpital Roger Salengro, Pôle De Réanimation: Dr Thibault Duburcq, Chu Lille, Surgical Critical Care, Department of Anesthesiology and Critical Care: Prof Eric Kipnis, Dr Perrine Bortolotti. Groupe Hospitalier Nord Essonne - Site Longjumeau, Réanimation Polyvalente: Dr Martial Thyrault, Dr Rémi Paulet. Groupe Hospitalier Paris Saint Joseph, Médecine Intensive et Réanimation: Dr François Philippart, Dr Marc Tran, Dr Cédric Bruel. Hôpital Beaujon, Department of Anesthesiology and Critical Care: Dr Emmanuel Weiss, Dr Sylvie Janny, Dr Arnaud Focrier. Hôpital De La Timone, Médecine Intensive Réanimation: Dr Marc Gainnier, Dr Jérémy Bourenne. Hôpital Edouard Herriot, Médecine Intensive-Réanimation: Dr Laurent Argaud, Dr Thomas Baudry. Hôpital Henri Mondor, Service De Réanimation Médicale: Pr Armand Mekonted Dessap, Dr Keyvan Razazi. Hôpital Louis Pasteur, Réanimation: Dr Pierre Kalfon, Mr Gaëtan Badre. Nimes University Hospital, Service Des Réanimations: Prof Jean-Yves Lefrant, Dr Claire Roger. Sud Essonne Hospital, Department of Intensive Care Medicine: Dr Shidasp Siami, Mrs Christelle Aparicio. University Hospital Of Poitiers, Surgical And Neuro Intensive Care Units: Dr Claire Dahyot-Fizelier, Dr Nadia Imzi. **Italy**—**National Coordinator:** Prof. Matteo Bassetti and Dr. Daniele
Our study revealed that there was no significant difference in the incidence of fungal HABSI between cirrhotic and non-cirrhotic patients. This finding is noteworthy as these infections are often concerning in cirrhotic patients as previous studies highlighted more invasive fungal infections in cirrhotic patients compared to non-cirrhotic patients, especially in an ICU setting [28, 29]. However, the results of our study suggest that cirrhotic patients may not be at a higher risk for fungal infections, which has important implications for clinical management strategies.

Our study highlights that critically ill cirrhotic patients with HABSI were associated with poorer outcomes, with a mortality rate reaching 45%, which was significantly higher than non-cirrhotic patients. This has already been highlighted for nosocomial infections in cirrhotic patients [30]. Active measures to prevent nosocomial infections, including HABSI, should be thoroughly applied to these vulnerable patients. This can be achieved through excellent infection prevention and control measures targeting the most important healthcare-associated infections, reducing the unnecessary use of proton pump inhibitors, avoiding the placement of intravascular and urinary catheters and limiting their duration [30, 31].

Our study has several limitations. First, ICUs in high income countries and European ICUs were overrepresented with three countries (France, UK and Turkey) recruiting 30% of patients, thus potentially limiting the generalizability of our results [2]. However, each continent was represented and included patients in our study. Second, pathogen identification and antimicrobial susceptibility testing was dependent on each center's laboratory, which limits the standardization of microbiological results [2]. Third, the causes and severity of cirrhosis could not be assessed, which could have influenced the outcome [13]. Fourth, data collection was performed by individual investigators in each ICU without on-site monitoring. This limitation was controlled by providing online checks through the electronic case report file and by monitoring data quality and coherence of the data for each case-report form [2]. Lastly, this is a secondary analysis of the Eurobact-II database, with the inherent risk of bias that such analyses may carry.

In summary, critically ill cirrhotic patients with HABSI have a higher mortality than those without cirrhosis. They present a specific microbiology, with more Gram-positive bacteria and especially more *E. faecium* bacteremia than non-cirrhotic patients. In these particular patients, empirical coverage of *E. faecium* should be considered. This should be confirmed by interventional studies specifically designed to determine the efficacy and safety of such antibiotic treatments in this high-risk population.

## Abbreviations

<table><tr><td>HABSI</td><td>Hospital-acquired bloodstream infections</td></tr><tr><td>ICU</td><td>intensive care unit</td></tr><tr><td>SAPSII</td><td>simplified acute physiology score II</td></tr><tr><td>SOFA</td><td>sequential organ failure assessment</td></tr><tr><td>OR</td><td>operating room</td></tr><tr><td>WBC</td><td>white blood cells</td></tr><tr><td>CRP</td><td>C-reactive protein</td></tr><tr><td>CVVHDF</td><td>continuous venovenous hemodiafiltration</td></tr><tr><td>SLEDD</td><td>Sustained low-efficiency daily dialysis</td></tr><tr><td>MDRO</td><td>multi-drug resistant organisms</td></tr></table>

## Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s13613-024-01299-x.

Supplementary Material 1

Supplementary Material 2

## Acknowledgements

The Eurobact 2 study group, National coordinators, scientific committee and participating intensive care units: **Middle East: Israel-National Coordinator:** Prof. Pierre Singer; **Participating ICU:** Rabin Medical Center Beilinson Hospital, General Intensive Care: Prof Pierre Singer, Dr Ilya Kagan, Dr Merav Rigler.
**Egypt:** **National Coordinator:** Dr. Adel Alsisi Cairo University Hospital (Qasr Al Ainy), Critical Care Department: Dr Adel Alsisi, Dr Amr Elhadidy, Dr Mina Barsoum.Medical Research Institute, Alexandria University, Biomedical Informatics and Medical Statistics (Icu): Dr Nermin Osman. Tanta University Hospital, Anaesthesia and Critical Care Department: Dr Tarek Mostafa. Tanta University Faculty of Medicine, Emergency Medicine and Traumatology Department: Dr Mohamed Elbahnasawy. Nasr City Health Insurance Hospital, Medical Icu: Dr Amer Aldhalia. Wingat Royal Hospital, Wingat Icu: Dr Omar Elmandouh. **Latin America: Mexico**—**National Coordinator:** Dr. Silvio A. Namendys-Silva; **Participating ICUs:** Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Division of Pulmonary, Anesthesia and Critical Care Medicine: Dr Jose G. Dominguez-Cherit, Dr Adrian Davalos-Alvarez, Dr Silvio A. Namendys-Silva. UMAE Hospital de Especialidades Antonio Fraga Mouret.
**Europe And Central Asia: Belgium**—**National Coordinator:** Dr. Liesbet De Bus; **Participating ICUs:** Ghent University Hospital, Intensive Care Unit: Dr Liesbet De Bus, Dr Jan De Waele. A.S.Z., Iz: Dr Isabelle Hollevoet. Az Nikolaas, Icu: Dr Wouter Denys. Centre Hospitalier De Jolimont, Soins Intensifs: Dr Jean-Baptiste Mesland, Dr Pierre Henin. Cliniques Universitaires Saint-Luc, UCLouvain, Soins Intensifs: Dr Xavier Wittebole. Uzbrussel, Intensieve Zorgen: Prof Elisabeth De Waele, Mrs Godelive Opdenacker. **Bosnia And Herzegovina:** **National Coordinator:** Dr. Pedja Kovacevic; **Participating ICUs:** University Clinical Centre of The Republic Of Srpska, Medical Intensive Care Unit: Dr Pedja Kovacevic, Dr Biljana Zlojutro. **France**—**National Coordinator:** Prof. Marc Leone; **Scientific Committee:** Prof. Jean-François Timsit, Prof. Etienne Ruppe, Mr. Stephane Ruckly, Prof. Philippe Montravers; Bichat Claude Bernard, Réanimation Médicale et Infectieuse: Prof Jean-François Timsit, Mme Juliette Patrier. Bichat-Claude Bernard Hospital, Ap-Hp, Anesthesiology And Critical Care Medicine Department, Dmu Parabol: Dr N.Zappela, Pr P. Montravers. Ch Annecy Genevois, Réanimation Polyvalente: Dr Etienne Escudier. Chu Lille, Hôpital Roger Salengro, Pôle De Réanimation: Dr Thibault Duburcq, Chu Lille, Surgical Critical Care, Department of Anesthesiology and Critical Care: Prof Eric Kipnis, Dr Perrine Bortolotti. Groupe Hospitalier Nord Essonne - Site Longjumeau, Réanimation Polyvalente: Dr Martial Thyrault, Dr Rémi Paulet. Groupe Hospitalier Paris Saint Joseph, Médecine Intensive et Réanimation: Dr François Philippart, Dr Marc Tran, Dr Cédric Bruel. Hôpital Beaujon, Department of Anesthesiology and Critical Care: Dr Emmanuel Weiss, Dr Sylvie Janny, Dr Arnaud Foucrier. Hôpital De La Timone, Médecine Intensive Réanimation: Dr Marc Gainnier, Dr Jérémy Bourenne. Hôpital Edouard Herriot, Médecine Intensive-Réanimation: Dr Laurent Argaud, Dr Thomas Baudry. Hôpital Henri Mondor, Service De Réanimation Médicale: Pr Armand Mekonted Dessap, Dr Keyvan Razazi. Hôpital Louis Pasteur, Réanimation: Dr Pierre Kalfon, Mr Gaëtan Badre. Nimes University Hospital, Service Des Réanimations: Prof Jean-Yves Lefrant, Dr Claire Roger. Sud Essonne Hospital, Department of Intensive Care Medicine: Dr Shidasp Siami, Mrs Christelle Aparicio. University Hospital Of Poitiers, Surgical And Neuro Intensive Care Units: Dr Claire Dahyot-Fizelier, Dr Nadia Imzi. **Italy**—**National Coordinator:** Prof. Matteo Bassetti and Dr. Daniele
Giacobbe; *Participating ICUs*: Città Della Salute E Della Scienza - Molinette, Anestesia E Rianimazione Universitaria: Dr Giorgia Montrucchio, Dr Gabriele Sales. Fondazione Policlinico Universitario A. Gemelli Irccs. Irccs Ospedale Policlinico San Martino, U.O. Anestesia E Rianimazione: Prof Daniele Roberto Giacobbe, Dr Angelo Gratarola, Dr Elisa Porcile, Dr Michele Mirabella. Policlinico Paolo Giaccone, Università Degli Studi Di Palermo, Terapia Intensiva Polivalente: Dr Andrea Cortegiani, Dr Mariachiara Ippolito, Dr Davide Bellina, Dr Andrea Di Guardo. **Poland**—National Coordinator: Dr. Adam Mikstacki; *Participating ICUs*: Szpital Wojewodzki W Opolu, Oddział Anestezjologii I Intensywnej Terapii: Dr Jozef Bojko, Dr Anna Kotkowska. Bieganskiego, Oddział Anestezjologii I Intensywnej Terapii - Osrodek Pozaustrojowych Technik Wspomagania Czynnosci Nerek I Wątroby: Prof Assoc Mariusz Peichota, Dr Iwona Pietraszek-Grzywaczewska. **Portugal**—National Coordinator: Prof José Artur Paiva. Scientific Committee: Prof. Pedro Póvoa. *Participating ICUs*: Centro Hospitalar Universitário do Porto, Sci 1: Dr Nádia Guimarães, Dr Madalena Alves. Hospital Curry Cabral, Intensive Care Medicine Department: Dr Tiago Duarte. Hospital Sao Francisco Xavier, CHLO, Unidade De Cuidados Intensivos Polivalente: Dr Vasco Costa, Dr Rui Pedro Cunha, CHULC, Hospital Sao José, Unidade de Urgência Médica: Dr Sara Ledo, Dr Joana Queiró. **Republic of Ireland**—National Coordinator: Prof Ignacio Martin-Loeches. *Participating ICUs*: St Jame's Hospital, Intensive Care Unit: Prof Ignacio Martin-Loeches, Dr Alessandra Bisanti. **Romania**—National Coordinator: Dr Liana Valeanu. *Participating ICUs*: Emergency Institute for Cardiovascular Diseases Prof. Dr. C. Iliescu, 1st Anesthesia and Intensive Care Department: Dr Liana Valeanu, Prof Serban Bubenek-Turconi. Fundeni Clinical Institute, Department of Anesthesia and Intensive Care: Prof Dana Tomescu, Dr Mihai Popescu, Dr Alexandra Marcu. **Germany**—National Coordinator: Prof. Hendrik Bracht *Participating ICUs*: University Hospital Ulm, Icu G1: Dr Hendrik Bracht, Dr Sandra Hoheisen. Jena University Hospital, Dept. Of Anesthesiology and Intensive Care Medicine: Dr Frank Bloos, Dr Daniel Thomas-Rueddel. Universitätsklinikum Leipzig, Medical Icu: Dr Sirak Petros, Dr Bastian Pasieka. University Hospital Heidelberg, Station 13 lopsis: Dr Simon Dubler, Dr Karsten Schmidt. University Hospital Muenster, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy: Dr Antje Gottschalk, Dr Carola Wempe. **Greece**—National Coordinator: Dr Kostoula Arvaniti. *Participating ICUs*: Papageorgiou Hospital, Intensive Care Unit: Dr Kostoula Arvaniti, Dr Dimitrios Smyrniotis. Agioi Anargiroi Hospital, Agioi Anargiroi Icu: Dr Vasiligi Psallida, Dr Georgios Fidisildis. Gh Imathia Veria, Icu: Dr Mariana Kristina Matei, Dr Leora Moldovan. Icu, Hygeia General Hospital: Dr Ilias Karaiskos, Dr Harry Paskalis. Katerini General Hospital, Gnk Icu: Dr Marina Oikonomou, Dr Evangelos Kogkopoulos. Konstantopoulion-Patision Hospital, Icu: Dr Charikleia Nikolaou, Dr Anastasios Sakkalis. University Hospital Attikon, National And Kapodistrian University Of Athens, Department Of Critical Care: Pr Georges Dimopoulos, Dr Maria Panagiota Almiroudi. University Hospital of Ioannina, Intensive Care Unit: Pr Vasilios Kouroulas, A/Pr Georgios Papathanakos. **Kazakhstan**—National Coordinator: Dr. Dmitriy Viderman. *Participating ICUs*: University Medical Center, National Research Oncology Center, Intensive Care Unit: Dr Dmitriy Viderman, Dr Yerlan Ymbetzhanov. **Russian Federation**—National Coordinator: Prof Alexey Gritsan; *Participating ICUs*: City Clinical N.I.Pirogov Hospital, Clinical Pharmacology: Dr Anastasia Anderzhanova, Dr Yulia Meleshkina. City Clinical N.I.Pirogov Hospital, Icu: Dr Marat Magomedov. Krasnoyarsk Regional Clinical Hospital, Dep. Anaesthesiology and Intensive Care 3: Dr Denis Gaigolnik. Privolzhskiy District Medical Center, Department Anesthesiology and Intensive Care: Dr Vladislav Belskiy, Dr Mikhail Furman. **Croatia**—National Coordinator: Dr Ina Filipovic-Grci University Hospital Centre Zagreb, Medical Intensive Care Unit: Prof Radovan Radonic, Dr Ana Vujaklija Brajkovic. **Spain**—National Coordinator: Dr. Ricard Ferrer; *Participating ICUs*: Vall D'herbon, Intensive Care Medicine: Dr Ricard Ferrer Rocca, Dr Maria Martinez, Dr Vanessa Casares. Hospital Clinic De Barcelona, Surgical Icu: Dr Ricard Mellado Artigas. Hospital Germans Trias I Pujol, Critical Care Unit: Prof, Dr Fernando Armestar, Dr Beatriz Catalan, Dr Regina Roig, Dr Laura Raguer, Dr María Dolores Quesada. Hospital Universitario Central De Asturia, Uci-Huca: Dr Lorena Forcelledo Espina, Dr Emilio Garcia Prieto. University Hospital Severo Ochoa, Intensive Care Unit: Dr Miguel Angel Blasco-Navalpotro, Dr Alberto Orejas Gallego. **Switzerland**—National Coordinator: Dr. Josef Prazak; Scientific Committee: Dr. Niccolò Buetti; *Participating ICUs*: Inselspital, Bern University Hospital, Department of Intensive Care Medicine: Dr Josef Prazak, Dr Stephan Jakob. Chuv, Service De Médecine Intensive Adulte: Dr Jl Pagani, Mrs S Abed-Maillard. **Turkey**—National Coordinator: Prof. Akova Murat, Dr. Abdullah Tarik Aslan; *Participating ICUs*: Hacettepe University of Faculty of Medicine, Intensive Care Unit(ICU): Dr Murat Akova, Dr Abdullah Tarik Aslan, Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Department of Anesthesiology: Dr Arif

Timuroglu. Acibadem Fulya Hospital, Infectious Diseases: Dr Sesin Kocagoz, Dr Hulya Kusoglu. Bitlis Government Central Hospital, Bitlis Icu: Dr Emine Kubra Dindar Demiray, Dr Sait Çolak. Duzce. Istanbul Medipol University, Kosuyolu Hospital, Infectious Diseases and Clinical Microbiology: Dr Mesut Yilmaz, Dr Burcu Tunay, Dr Rumeysa Cakmak. Medipol Mega University Hospitals Complex, Department of Anesthesiology and Reanimation: Dr Cem Erdoğan. University of Health Sciences Diskapi Yildirim Beyazit Training and Research Hospital, The Department of Infectious Diseases and Clinical Microbiology and ICU: Dr Yunus Gürbüz, Dr Nilgün Altin. Turgut Ozel Medical Center, Department of Infectious Diseases and Clinical Microbiology: Dr Yasar Bayindir, Dr Yasemin Ersoy. University of Health Sciences Istanbul Umraniye Training and Research Hospital, Anaestesia and Reanimation: Dr Senay Goksu, Dr Ahmet Akyl. University of Health Sciences, Kartal Dr. Lutfi Kirdar Training and Research Hospital, Infectious Diseases and Clinical Microbiology: Prof Ayse Batirel, Dr Sabahat Cagan Aktas. **The United Kingdom**—National Coordinator: Dr. Andrew Conway Morris; *Participating ICUs*: Addenbrooke's Hospital, John V Farman Intensive Care Unit: Dr Andrew Conway Morris, Dr Matthew Routledge. Addenbrooke's Hospital, Neurocritical Care Unit (NCCU): Dr Andrew Conway Morris, Dr Ari Ercole. Darlington Memorial Hospital Intensive Care Unit, County Durham and Darlington NHS Foundation Trust: Dr Amanda Cowton, Dr Melanie Kent. Croydon University Hospital, Critical Care Unit: Dr Ashok Raj, Dr Artemis Zormpa, Dr George Tinasandidis, Mrs Reena Khade. Department Of Anaesthetics and Intensive Care Medicine, Queen Elizabeth Hospital Birmingham: Dr Tomasz Torlinski, Dr Randeep Mulhi, Dr Shraddha Goyal, Dr Manan Bajaj, Dr Marina Soltan, Dr Aimee Yonan, Dr Rachael Dolan. Department Of Microbiology, Queen Elizabeth Hospital Birmingham: Dr Aimee Johnson. Freeman Hospital, ICCU 37: Dr Caroline Macfie, Dr James Lennard. Royal Went Hospital, Critical Care Unit: Dr Tomas Szakmy, Dr Tom Baumer. Royal London Hospital, Adult Critical Care Unit: Dr Rebecca Longbottom, Dr Daniel Hall. Royal Marsden NHS Foundation Trust, Critical Care Unit: Dr Kate Tatham, Dr S Loftus, Dr A Husain, Dr E Black, Dr S Jhanji, Dr R Rao Baikady. Royal Victoria Hospital, Belfast, Regional Intensive Care Unit: Dr Peter Mcguigan, Dr Rachel Mckee. Sandwell and West Birmingham Hospitals NHS Trust, Intensive Care Unit: Dr Santha Kannan, Dr Supriya Antolikar, Dr Nicholas Marsden. St Mary's Hospital - Imperial College NHS Trust, Intensive Care Unit, Level 11: Dr Valentina Della Torre, Ms Dorota Banach. Warwick Hospital, Intensive Care Unit: Dr Ben Attwood, Dr Jamie Patel. West Suffolk NHS Foundation Trust, Critical Care: Dr Rebecca E Tilley, Miss Sally K Humphreys. Wirral University Teaching Hospital, Intensive Care Unit: Dr Paul Jean Renaud **East Asia and Pacific: Australia**—National Coordinator: A/Prof. Alexis Tabah; Scientific Committee: Prof. Jeffrey Lipman; *Participating ICUs*: Redcliffe Hospital, ICU: Prof. Alexis Tabah, Dr Hamish Pollock, Dr Ben Margetts. Mater Hospital, And Mater Research Institute – The University of Queensland. Mater Misericordiae Limited, The Department of Intensive Care: Dr Anne Ledtischke, Miss Mackenzie Finnis. Mater Private Hospital, And Mater Research Institute – The University of Queensland. Mater Misericordiae, The Department of Intensive Care: Dr Anne Ledtischke, Miss Mackenzie Finnis. Bankstown-Lidcombe Hospital, Intensive Care Unit: Dr Jyotsna Dwivedi, Dr Manoj Saxena. Lyell Mcewin Hospital, Lyell Mcewin Hospital Intensive Care Unit: Dr Vishwanath Biradar, Mrs Natalie Soar. The Prince Charles Hospital, Adult Intensive Care Services: Dr Mahesh Ramanan. Princess Alexandra Hospital, Intensive Care: Dr James Walsham, Mr Jason Meyer. **Japan**—National Coordinator: Dr. Yoshiro Hayashi; *Participating ICUs*: Kameda Medical Center, Department of Intensive Care Medicine: Dr Yoshiro Hayashi, Dr Toshiyuki Karumai. **Taiwan**—National Coordinator: Dr. Tony Yu-Chang Yeh *Participating ICUs*: National Taiwan University Hospital, Sicu: Dr Yu Chang Yeh, Dr Nai-Kuan Chou. National Cheng Kung University Hospital, Division of Critical Care Medicine, Department of Internal Medicine: Dr Cong-Tat Cia. Mackay Memorial Hospital, Department of Critical Care Medicine: Dr Ting-Yu Hu, Dr Li-Kuo Kuo. National Taiwan University Hospital, Department of Internal Medicine, Micu: Dr Shih-Chi Ku. **Republic Of Korea**—National Coordinator: Dr Kyeongman Jeon. *Participating ICUs*: Samsung Medical Center, Medical Icu: Dr Kyeongman Jeon. Seoul National University Hospital, Medical Icu: Dr Sang-Min Lee. Hallym University Sacred Heart Hospital, Micu: Dr Sunghoon Park. Micu, Chonbuk National University Hospital: Prof Dr Seung Yong Park. Seoul National University Bundang Hospital, Medical Icu: Dr Sung Yoon Lim. **Asia: India**—National Coordinator: Prof. Mohan Gurjar; *Participating ICUs*: Medica Superspecialty Hospital, Medica Institute of Critical Care: Dr Payel Bose, Dr Avijatri Datta. **Bangladesh**—National Coordinator: Dr Raihan Rabbani. *Participating ICUs*: General Icu, Dhaka: Dr Raihan Rabbani, Dr Shihan Mahmud Redwanul Huq. Asgar Ali Hospital, Critical Care Medicine: Dr Rajib Hasan, Dr Mohammad Motiul Islam. **Brunei**—National Coordinator: Dr. Khalid Mk
Giacobbe; *Participating ICUs*: Città Della Salute E Della Scienza - Molinette, Anestesia E Rianimazione Universitaria: Dr Giorgia Montrucchio, Dr Gabriele Sales. Fondazione Policlinico Universitario A. Gemelli Irccs. Irccs Ospedale Policlinico San Martino, U.O. Anestesia E Rianimazione: Prof Daniele Roberto Giacobbe, Dr Angelo Gratarola, Dr Elisa Porcile, Dr Michele Mirabella. Policlinico Paolo Giaccone, Università Degli Studi Di Palermo, Terapia Intensiva Polivalente: Dr Andrea Cortegiani, Dr Mariachiara Ippolito, Dr Davide Bellina, Dr Andrea Di Guardo. **Poland**—*National Coordinator*: Dr. Adam Mikstacki; *Participating ICUs*: Szpital Wojewodzki W Opolu, Oddział Anestezjologii I Intensywnej Terapii: Dr Jozef Bojko, Dr Anna Kotkowska. Bieganskiego, Oddział Anestezjologii I Intensywnej Terapii - Osrodek Pozaustrojowych Technik Wspomagania Czynnosci Nerek I Wątroby: Prof Assoc Mariusz Peichota, Dr Iwona Pietraszek-Grzywaczewska. **Portugal**—*National Coordinator*: Prof José Artur Paiva. *Scientific Committee*: Prof. Pedro Póvoa. *Participating ICUs*: Centro Hospitalar Universitário do Porto, Sci 1: Dr Nádia Guimarães, Dr Madalena Alves. Hospital Curry Cabral, Intensive Care Medicine Department: Dr Tiago Duarte. Hospital Sao Francisco Xavier, CHLO, Unidade De Cuidados Intensivos Polivalente: Dr Vasco Costa, Dr Rui Pedro Cunha, CHULC, Hospital Sao José, Unidade de Urgência Médica: Dr Sara Ledo, Dr Joana Queiró. **Republic of Ireland**—*National Coordinator*: Prof Ignacio Martin-Loeches. *Participating ICUs*: St Jame's Hospital, Intensive Care Unit: Prof Ignacio Martin-Loeches, Dr Alessandra Bisanti. **Romania**—*National Coordinator*: Dr Liana Valeanu. *Participating ICUs*: Emergency Institute for Cardiovascular Diseases Prof. Dr. C. Iliescu, 1st Anesthesia and Intensive Care Department: Dr Liana Valeanu, Prof Serban Bubenek-Turconi. Fundeni Clinical Institute, Department of Anesthesia and Intensive Care: Prof Dana Tomescu, Dr Mihai Popescu, Dr Alexandra Marcu. **Germany**—*National Coordinator*: Prof. Hendrik Bracht *Participating ICUs*: University Hospital Ulm, Icu G1: Dr Hendrik Bracht, Dr Sandra Hoheisen. Jena University Hospital, Dept. Of Anesthesiology and Intensive Care Medicine: Dr Frank Bloos, Dr Daniel Thomas-Rueddel. Universitätsklinikum Leipzig, Medical Icu: Dr Sirak Petros, Dr Bastian Pasieka. University Hospital Heidelberg, Station 13 lopsis: Dr Simon Dubler, Dr Karsten Schmidt. University Hospital Muenster, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy: Dr Antje Gottschalk, Dr Carola Wempe. **Greece**—*National Coordinator*: Dr. Kostoula Arvaniti. *Participating ICUs*: Papageorgiou Hospital, Intensive Care Unit: Dr Kostoula Arvaniti, Dr Dimitrios Smyrniotis. Agioi Anargiroi Hospital, Agioi Anargiroi Icu: Dr Vasiligi Psallida, Dr Georgios Fidisidis. Gh Imathia Veria, Icu: Dr Mariana Kristina Matei, Dr Leora Moldovan. Icu, Hygeia General Hospital: Dr Ilias Karaiskos, Dr Harry Paskalis. Katerini General Hospital, Gnk Icu: Dr Marina Oikonomou, Dr Evangelos Kogkopoulos. Konstantopoulion-Patision Hospital, Icu: Dr Charikleia Nikolaou, Dr Anastasios Sakkalis. University Hospital Attikon, National And Kapodistrian University Of Athens, Department Of Critical Care: Pr Georges Dimopoulos, Dr Maria Panagiota Almiroudi. University Hospital of Ioannina, Intensive Care Unit: Pr Vasilios Kouroulas, A/Pr Georgios Papathanakos. **Kazakhstan**—*National Coordinator*: Dr. Dmitriy Viderman. *Participating ICUs*: University Medical Center, National Research Oncology Center, Intensive Care Unit: Dr Dmitriy Viderman, Dr Yerlan Ymbetzhanov. **Russian Federation**—*National Coordinator*: Prof Alexey Gritsan; *Participating ICUs*: City Clinical N.I.Pirogov Hospital, Clinical Pharmacology: Dr Anastasia Anderzhanova, Dr Yulia Meleshkina. City Clinical N.I.Pirogov Hospital, Icu: Dr Marat Magomedov. Krasnoyarsk Regional Clinical Hospital, Dep. Anaesthesiology and Intensive Care 3: Dr Denis Gaigolnik. Privolzhskiy District Medical Center, Department Anesthesiology and Intensive Care: Dr Vladislav Belskiy, Dr Mikhail Furman. **Croatia**—*National Coordinator*: Dr Ina Filipovic-Grci University Hospital Centre Zagreb, Medical Intensive Care Unit: Prof Radovan Radonic, Dr Ana Vujaklija Brajkovic. **Spain**—*National Coordinator*: Dr. Ricard Ferrer; *Participating ICUs*: Vall D'herbon, Intensive Care Medicine: Dr Ricard Ferrer Rocca, Dr Maria Martinez, Dr Vanessa Casares. Hospital Clinic De Barcelona, Surgical Icu: Dr Ricard Mellado Artigas. Hospital Germans Trias I Pujol, Critical Care Unit: Prof, Dr Fernando Armestar, Dr Beatriz Catalan, Dr Regina Roig, Dr Laura Raguer, Dr María Dolores Quesada. Hospital Universitario Central De Asturia, Uci-Huca: Dr Lorena Forcelledo Espina, Dr Emilio Garcia Prieto. University Hospital Severo Ochoa, Intensive Care Unit: Dr Miguel Angel Blasco-Navalpotro, Dr Alberto Orejas Gallego. **Switzerland**—*National Coordinator*: Dr. Josef Prazak; *Scientific Committee*: Dr. Niccolò Buetti; *Participating ICUs*: Inselspital, Bern University Hospital, Department of Intensive Care Medicine: Dr Josef Prazak, Dr Stephan Jakob. Chuv, Service De Médecine Intensive Adulte: Dr Jl Pagani, Mrs S Abed-Maillard. **Turkey**—*National Coordinator*: Prof. Akova Murat, Dr. Abdullah Tarik Aslan; *Participating ICUs*: Hacettepe University of Faculty of Medicine, Intensive Care Unit(ICU): Dr Murat Akova, Dr Abdullah Tarik Aslan, Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Department of Anesthesiology: Dr Arif

Timuroglu. Acibadem Fulya Hospital, Infectious Diseases: Dr Sesin Kocagoz, Dr Hulya Kusoglu. Bitlis Government Central Hospital, Bitlis Icu: Dr Emine Kubra Dindar Demiray, Dr Sait Çolak. Duzce. Istanbul Medipol University, Kosuyolu Hospital, Infectious Diseases and Clinical Microbiology: Dr Mesut Yilmaz, Dr Burcu Tunay, Dr Rumeysa Cakmak. Medipol Mega University Hospitals Complex, Department of Anesthesiology and Reanimation: Dr Cem Erdoğan. University of Health Sciences Diskapi Yildirim Beyazit Training and Research Hospital, The Department of Infectious Diseases and Clinical Microbiology and ICU: Dr Yunus Gürbüz, Dr Nilgün Altin. Turgut Ozel Medical Center, Department of Infectious Diseases and Clinical Microbiology: Dr Yasar Bayindir, Dr Yasemin Ersoy. University of Health Sciences Istanbul Umraniye Training and Research Hospital, Anaestesia and Reanimation: Dr Senay Goksu, Dr Ahmet Akyl. University of Health Sciences, Kartal Dr. Lutfi Kirdar Training and Research Hospital, Infectious Diseases and Clinical Microbiology: Prof Ayse Batirel, Dr Sabahat Cagan Aktas. **The United Kingdom**—*National Coordinator*: Dr. Andrew Conway Morris; *Participating ICUs*: Addenbrooke's Hospital, John V Farman Intensive Care Unit: Dr Andrew Conway Morris, Dr Matthew Routledge. Addenbrooke's Hospital, Neurocritical Care Unit (NCCU): Dr Andrew Conway Morris, Dr Ari Ercole. Darlington Memorial Hospital Intensive Care Unit, County Durham and Darlington NHS Foundation Trust: Dr Amanda Cowton, Dr Melanie Kent. Croydon University Hospital, Critical Care Unit: Dr Ashok Raj, Dr Artemis Zormpa, Dr George Tinasandidis, Mrs Reena Khade. Department Of Anaesthetics and Intensive Care Medicine, Queen Elizabeth Hospital Birmingham: Dr Tomasz Torlinski, Dr Randeep Mulhi, Dr Shraddha Goyal, Dr Manan Bajaj, Dr Marina Soltan, Dr Aimee Yonan, Dr Rachael Dolan. Department Of Microbiology, Queen Elizabeth Hospital Birmingham: Dr Aimee Johnson. Freeman Hospital, ICCU 37: Dr Caroline Macfie, Dr James Lennard. Royal Went Hospital, Critical Care Unit: Dr Tomas Szakmy, Dr Tom Baumer. Royal London Hospital, Adult Critical Care Unit: Dr Rebecca Longbottom, Dr Daniel Hall. Royal Marsden NHS Foundation Trust, Critical Care Unit: Dr Kate Tatham, Dr S Loftus, Dr A Husain, Dr E Black, Dr S Jhanji, Dr R Rao Baikady. Royal Victoria Hospital, Belfast, Regional Intensive Care Unit: Dr Peter Mcguigan, Dr Rachel Mckee. Sandwell and West Birmingham Hospitals NHS Trust, Intensive Care Unit: Dr Santhana Kannan, Dr Supriya Antolikar, Dr Nicholas Marsden. St Mary's Hospital - Imperial College NHS Trust, Intensive Care Unit, Level 11: Dr Valentina Della Torre, Ms Dorota Banach. Warwick Hospital, Intensive Care Unit: Dr Ben Attwood, Dr Jamie Patel. West Suffolk NHS Foundation Trust, Critical Care: Dr Rebecca E Tilley, Miss Sally K Humphreys. Wirral University Teaching Hospital, Intensive Care Unit: Dr Paul Jean Renaud **East Asia and Pacific**: Australia—*National Coordinator*: A/Prof. Alexis Tabah; *Scientific Committee*: Prof. Jeffrey Lipman; *Participating ICUs*: Redcliffe Hospital, ICU: Prof. Alexis Tabah, Dr Hamish Pollock, Dr Ben Margetts. Mater Hospital, And Mater Research Institute – The University of Queensland. Mater Misericordiae Limited, The Department of Intensive Care: Dr Anne Ledtischke, Miss Mackenzie Finnis. Mater Private Hospital, And Mater Research Institute – The University of Queensland. Mater Misericordiae, The Department of Intensive Care: Dr Anne Ledtischke, Miss Mackenzie Finnis. Bankstown-Lidcombe Hospital, Intensive Care Unit: Dr Jyotsna Dwivedi, Dr Manoj Saxena. Lyell Mcewin Hospital, Lyell Mcewin Hospital Intensive Care Unit: Dr Vishwanath Biradar, Mrs Natalie Soar. The Prince Charles Hospital, Adult Intensive Care Services: Dr Mahesh Ramanan. Princess Alexandra Hospital, Intensive Care: Dr James Walsham, Mr Jason Meyer. **Japan**—*National Coordinator*: Dr. Yoshiro Hayashi; *Participating ICUs*: Kameda Medical Center, Department of Intensive Care Medicine: Dr Yoshiro Hayashi, Dr Toshiyuki Karumai. **Taiwan**—*National Coordinator*: Dr. Tony Yu-Chang Yeh *Participating ICUs*: National Taiwan University Hospital, Sicu: Dr Yu Chang Yeh, Dr Nai-Kuan Chou. National Cheng Kung University Hospital, Division of Critical Care Medicine, Department of Internal Medicine: Dr Cong-Tat Cia. Mackay Memorial Hospital, Department of Critical Care Medicine: Dr Ting-Yu Hu, Dr Li-Kuo Kuo. National Taiwan University Hospital, Department of Internal Medicine, Micu: Dr Shih-Chi Ku. **Republic Of Korea**—*National Coordinator*: Dr Kyeongman Jeon. *Participating ICUs*: Samsung Medical Center, Medical Icu: Dr Kyeongman Jeon. Seoul National University Hospital, Medical Icu: Dr Sang-Min Lee. Hallym University Sacred Heart Hospital, Micu: Dr Sunghoon Park. Micu, Chonbuk National University Hospital: Prof Dr Seung Yong Park. Seoul National University Bundang Hospital, Medical Icu: Dr Sung Yoon Lim. **Asia: India**—*National Coordinator*: Prof. Mohan Gurjar; *Participating ICUs*: Medica Superspecialty Hospital, Medica Institute of Critical Care: Dr Payel Bose, Dr Avijatri Datta. **Bangladesh**—*National Coordinator*: Dr Raihan Rabbani. *Participating ICUs*: General Icu, Dhaka: Dr Raihan Rabbani, Dr Shihan Mahmud Redwanul Huq. Asgar Ali Hospital, Critical Care Medicine: Dr Rajib Hasan, Dr Mohammad Motiul Islam. **Brunei**—*National Coordinator*: Dr. Khalid Mk
Nafees. *Participating ICUs*: Raja Isteri Pengiran Anak Saleha Hospital, Icu1: Dr Nurhikmahtul Agilah Haji Abd Rashid, Dr Haji Adi Muhamad Ibnu Walid.

**China**— *National Coordinator*: Dr. Qiu Haibo and Dr. Jianfeng Xie Qilu Hospital of Shandong University, Department of Critical Care Medicine: Dr Xiaomei Chen, Dr Hao Wang. Hebei Petrochina Central Hospital, Intensive Care Unit: Dr Peng Zhao, Dr Juan Zhao. Hangzhou Second Hospital, Affiliated Hospital of Hangzhou Normal University: Prof Qiu Wusi, Miss Chen Mingmin. **Hong Kong**— *National Coordinator*: Dr. Lowell Ling *Participating ICUs*: The Chinese University of Hong Kong, Prince of Wales Hospital, Department Of Anaesthesia And Intensive Care: Dr Lowell Ling. **Singapore**— *National Coordinator*: A/Prof Andrea Lay Hoon Kwa, Dr Qing Yuan Goh *Participating ICUs*: Singapore General Hospital, Surgical Intensive Care Unit: Dr Qing Yuan Goh, A/Prof Shin Yi Ng. Singapore General Hospital, Neurosurgical Intensive Care Unit: Dr Sui An Lie, A/Prof Andrea Lay Hoon Kwa. Singapore General Hospital, Medical Intensive Care Unit: Dr Ken Junyang Goh. Changi General Hospital, Medical Intensive Care Unit: Dr Jessica Lishan Quah, Dr Kangqi Ng. Changi General Hospital, Surgical Intensive Care Unit: Dr Louis Xiang Long Ng. **Thailand**— *National Coordinator*: Prof (Associate) Phunsup Wongsurakiat. *Participating ICUs*: Siriraj Hospital, Mahidol University, Critical Respiratory Care Unit, Department of Medicine: Prof (Associate) Phunsup Wongsurakiat. Vajira Hospital, Department of Internal Medicine: Dr Yutthana Apichatbutr, Dr Supattra Chiewroongroj.

**North America**: **Canada**— *National Coordinator*: Prof. Wendy Sligl. *Participating ICUs*: University of Alberta Hospital, General Systems Intensive Care Unit (Gsicu): Dr Wendy Sligl, Nadia Baig, Lorena McCoshen. **South Africa**— *National Coordinator*: Prof. Mervyn Mer. *Participating ICUs*: Charlotte Maxeke Johannesburg Academic Hospital, Ward 576: Prof Mervyn Mer, Mrs Melanie Mc Cree.

**Other 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.

## Author contributions

Conceptualization, HW and NB; methodology, HW, SR and NB; formal analysis, HW and NB; data curation, HW, NB, JFT, AT, FB; writing—original draft preparation, HW and NB; writing—review and editing, all authors contributed; visualization, HW, NB, JFT, AT; supervision, NB. All authors have read and approved the final manuscript.

## Funding

The Eurobact-2 database received research grants 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. This report was prepared with no specific funding.

Open access funding provided by University of Geneva

## Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

## Declarations

### Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics Committee of the Royal Brisbane & Women's Hospital Human Research (LNR/2019/QRBW/48,376). Each study site then obtained ethical and governance approvals according to the local regulations in place.

### Consent for publication

Not applicable.

### Competing interests

M. Bassetti reports COI out of the submitted work including research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Angelini, BioMérieux, Cidara, Menarini, MSD, Pfizer, and Shionogi. F Barbier reports COI out of the submitted work including lecture fees from MSD and BioMérieux, conference invitation from Pfizer. J-F. Timsit reports COI out of

the submitted work, including ad boards (Pfizer, PSD, ASPEN, Gilead), lectures (BioMérieux, MSD, Pfizer, Shionogi, Mundipharma, Gilead, Qiagen) and research grants (MSD, Pfizer, Thermo Fischer Scientific).

## Author details

¹Division of Critical Care, Department of Acute Medicine, University Hospital of Geneva, University of Geneva, Geneva, Switzerland

²Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada

³Intensive Care Unit, Redcliffe Hospital, Brisbane, Australia

⁴Queensland Critical Care Research Network (QCCRN), Brisbane, QLD, Australia

⁵Queensland University of Technology, Brisbane, QLD, Australia

⁶Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia

⁷Service de Médecine Intensive-Réanimation, Centre Hospitalier Régional d'Orléans, Orléans, France

⁸Université de Paris, INSERM, IAME UMR 1137, Paris 75018, France

⁹ICUREsearch, Biometry, Fontaine 38600, France

¹⁰Department of Infectious Diseases, Hacettepe University School of Medicine, Ankara, Turkey

¹¹Department of Anesthesiology and Intensive Care Unit, Hospital Nord, Aix Marseille University, Assistance Publique Hôpitaux Universitaires de Marseille, Marseille, France

¹²Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK

¹³Division of Immunology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QQ, UK

¹⁴JVF Intensive Care Unit, Addenbrooke's Hospital, Cambridge, Hills Road, Cambridge CB2 0QQ, UK

¹⁵Infectious Diseases Clinic, Department of Health Sciences, University of Genoa and Ospedale Policlinico San Martino, Genoa, Italy

¹⁶Intensive Care Unit, Papageorgiou University Affiliated Hospital, Thessaloniki, Greece

¹⁷Intensive Care Department, SODIR-VHIR Research Group, Vall d'Hebron University Hospital, Barcelona, Spain

¹⁸Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium

¹⁹Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

²⁰Intensive Care Medicine Department, Centro Hospitalar Universitário São João (CHUSJ), Porto, Portugal

²¹Department of Medicine, Faculty of Medicine, University of Porto (FMUP), Porto, Portugal

²²Central Interdisciplinary Emergency Medicine, University Hospital Ulm, Ulm, Germany

²³Faculty of Health Sciences, Poznan University of Medical Sciences, Poznan, Poland

²⁴Department of Anaesthesiology and Intensive Therapy, Regional Hospital in Poznan, Poznan, Poland

²⁵ICU Department, Prime Hospital, Dubai, United Arab Emirates

²⁶Critical Care Department, Faculty of Medicine, Cairo University, Cairo, Egypt

²⁷Cardiac Anesthesiology and Intensive Care Department I, Emergency Institute for Cardiovascular Diseases Prof. Dr. C. C. Iliescu, Bucharest, Romania

²⁸Department of Intensive Care Medicine, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland

²⁹Université Paris- Cité, INSERM, IAME UMR 1137, Paris 75018, France

³⁰Medical and Infectious Diseases Intensive Care Unit, AP-HP, Bichat-Claude Bernard University Hospital, Paris, France

³¹Infection Control Program and World Health Organization Collaborating Centre on Patient Safety, Faculty of Medicine, University Hospitals, University of Geneva, Geneva, Switzerland

Received: 12 December 2023 / Accepted: 19 April 2024

Published online: 02 May 2024
Nafees. *Participating ICUs*: Raja Isteri Pengiran Anak Saleha Hospital, Icu1: Dr NurhikmahtulAQilah Haji Abd Rashid, Dr Haji Adi Muhamad Ibnu Walid.

**China**— *National Coordinator*: Dr. Qiu Haibo and Dr. Jianfeng Xie Qilu Hospital of Shandong University, Department of Critical Care Medicine: Dr Xiaomei Chen, Dr Hao Wang. Hebei Petrochina Central Hospital, Intensive Care Unit: Dr Peng Zhao, Dr Juan Zhao. Hangzhou Second Hospital, Affiliated Hospital of Hangzhou Normal University: Prof Qiu Wusi, Miss Chen Mingmin. **Hong Kong**— *National Coordinator*: Dr. Lowell Ling *Participating ICUs*: The Chinese University of Hong Kong, Prince of Wales Hospital, Department Of Anaesthesia And Intensive Care: Dr Lowell Ling. **Singapore**— *National Coordinator*: A/Prof Andrea Lay Hoon Kwa, Dr Qing Yuan Goh *Participating ICUs*: Singapore General Hospital, Surgical Intensive Care Unit: Dr Qing Yuan Goh, A/Prof Shin Yi Ng. Singapore General Hospital, Neurosurgical Intensive Care Unit: Dr Sui An Lie, A/Prof Andrea Lay Hoon Kwa. Singapore General Hospital, Medical Intensive Care Unit: Dr Ken Junyang Goh. Changi General Hospital, Medical Intensive Care Unit: Dr Jessica Lishan Quah, Dr Kangqi Ng. Changi General Hospital, Surgical Intensive Care Unit: Dr Louis Xiang Long Ng. **Thailand**— *National Coordinator*: Prof (Associate) Phunsup Wongsurakiat. *Participating ICUs*: Siriraj Hospital, Mahidol University, Critical Respiratory Care Unit, Department of Medicine: Prof (Associate) Phunsup Wongsurakiat. Vajira Hospital, Department of Internal Medicine: Dr Yutthana Apichatbutr, Dr Supattra Chiewroongroj.

**North America:** Canada— *National Coordinator*: Prof. Wendy Sligl. *Participating ICUs*: University of Alberta Hospital, General Systems Intensive Care Unit (Gsicu): Dr Wendy Sligl, Nadia Baig, Lorena McCoshen. **South Africa**— *National Coordinator*: Prof. Mervyn Mer. *Participating ICUs*: Charlotte Maxeke Johannesburg Academic Hospital, Ward 576: Prof Mervyn Mer, Mrs Melanie Mc Cree.

**Other 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.

## Author contributions

Conceptualization, HW and NB; methodology, HW, SR and NB; formal analysis, HW and NB; data curation, HW, NB, JFT, AT, FB; writing—original draft preparation, HW and NB; writing—review and editing, all authors contributed; visualization, HW, NB, JFT, AT; supervision, NB. All authors have read and approved the final manuscript.

## Funding

The Eurobact-2 database received research grants 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. This report was prepared with no specific funding.

Open access funding provided by University of Geneva

## Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

## Declarations

### Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics Committee of the Royal Brisbane & Women's Hospital Human Research (LNR/2019/QRBW/48/376). Each study site then obtained ethical and governance approvals according to the local regulations in place.

### Consent for publication

Not applicable.

### Competing interests

M. Bassetti reports COI out of the submitted work including research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Angelini, BioMérieux, Cidara, Menarini, MSD, Pfizer, and Shionogi. F Barbier reports COI out of the submitted work including lecture fees from MSD and BioMérieux, conference invitation from Pfizer. J-F. Timsit reports COI out of

the submitted work, including ad boards (Pfizer, PSD, ASPEN, Gilead), lectures (BioMérieux, MSD, Pfizer, Shionogi, Mundipharma, Gilead, Qiagen) and research grants (MSD, Pfizer, Thermo Fischer Scientific).

## Author details

¹Division of Critical Care, Department of Acute Medicine, University Hospital of Geneva, University of Geneva, Geneva, Switzerland

²Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada

³Intensive Care Unit, Redcliffe Hospital, Brisbane, Australia

⁴Queensland Critical Care Research Network (QCCRN), Brisbane, QLD, Australia

⁵Queensland University of Technology, Brisbane, QLD, Australia

⁶Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia

⁷Service de Médecine Intensive-Réanimation, Centre Hospitalier Régional d'Orléans, Orléans, France

⁸Université de Paris, INSERM, IAME UMR 1137, Paris 75018, France

⁹ICUREsearch, Biometry, Fontaine 38600, France

¹⁰Department of Infectious Diseases, Hacettepe University School of Medicine, Ankara, Turkey

¹¹Department of Anesthesiology and Intensive Care Unit, Hospital Nord, Aix Marseille University, Assistance Publique Hôpitaux Universitaires de Marseille, Marseille, France

¹²Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK

¹³Division of Immunology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QQ, UK

¹⁴JVF Intensive Care Unit, Addenbrooke's Hospital, Cambridge, Hills Road, Cambridge CB2 0QQ, UK

¹⁵Infectious Diseases Clinic, Department of Health Sciences, University of Genoa and Ospedale Policlinico San Martino, Genoa, Italy

¹⁶Intensive Care Unit, Papageorgiou University Affiliated Hospital, Thessaloniki, Greece

¹⁷Intensive Care Department, SODIR-VHIR Research Group, Vall d'Hebron University Hospital, Barcelona, Spain

¹⁸Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium

¹⁹Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

²⁰Intensive Care Medicine Department, Centro Hospitalar Universitário São João (CHUSJ), Porto, Portugal

²¹Department of Medicine, Faculty of Medicine, University of Porto (FMUP), Porto, Portugal

²²Central Interdisciplinary Emergency Medicine, University Hospital Ulm, Ulm, Germany

²³Faculty of Health Sciences, Poznan University of Medical Sciences, Poznan, Poland

²⁴Department of Anaesthesiology and Intensive Therapy, Regional Hospital in Poznan, Poznan, Poland

²⁵ICU Department, Prime Hospital, Dubai, United Arab Emirates

²⁶Critical Care Department, Faculty of Medicine, Cairo University, Cairo, Egypt

²⁷Cardiac Anesthesiology and Intensive Care Department I, Emergency Institute for Cardiovascular Diseases Prof. Dr. C. C. Iliescu, Bucharest, Romania

²⁸Department of Intensive Care Medicine, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland

²⁹Université Paris- Cité, INSERM, IAME UMR 1137, Paris 75018, France

³⁰Medical and Infectious Diseases Intensive Care Unit, AP-HP, Bichat-Claude Bernard University Hospital, Paris, France

³¹Infection Control Program and World Health Organization Collaborating Centre on Patient Safety, Faculty of Medicine, University Hospitals, University of Geneva, Geneva, Switzerland

Received: 12 December 2023 / Accepted: 19 April 2024

Published online: 02 May 2024
## References

1. Tabah A, Koulenti D, Laupland K, Misset B, Valles J, Bruzzi De Carvalho F, et al. Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med. 2012;38:1930–45. https://doi.org/10.1007/s00134-012-2695-9

2. Tabah A, Buetti N, Staiquly Q, Ruckly S, Akova M, Aslan AT, et al. Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study. Intensive Care Med. 2023;49:178–90. https://doi.org/10.1007/s00134-022-06944-2

3. Merli M, Lucidi C, Giannelli V, Giusto M, Riggio O, Falcone M, et al. Cirrhotic patients are at risk for health care-associated bacterial infections. Clin Gastroenterol Hepatol. 2010;8:979–e9851. https://doi.org/10.1016/j.cgh.2010.06.024

4. Bajaj JS, O'Leary JG, Tandon P, Wong F, Garcia-Tsao G, Kamath PS, Biggins SW, Lai JC, Vargas HE, Maliakkal B, Fallon MB, Thuluvath PJ, Subramanian RM, Thacker LRRK. Outcomes in hospitalized patients with nosocomial infections are frequent and negatively impact outcomes in hospitalized patients with cirrhosis. Am J Gastroenterol. 2019;3:1091–100. https://doi.org/10.14309/ajg.0000000000000280.Nosocomial

5. D'oliveira RAC, Pereira LCD, Codes L, Rocha M, de Bittencourt S. Analysis of healthcare associated and hospital acquired infections in critically ill patients with cirrhosis. Arq Gastroenterol. 2022;59:102–9. https://doi.org/10.1590/S0004-2803.202200001-8

6. Bunchorntavakul C, Chamroonkul N, Chavalitdhamrong D. Bacterial infections in cirrhosis: a critical review and practical guidance. World J Hepatol. 2016;8:307–21. https://doi.org/10.4254/wjh.v8.i6.307

7. Fernández J, Acevedo J, Castro M, García O, Rodríguez de Lope C, Roca D, et al. Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study. Hepatology. 2012;55:1551–61. https://doi.org/10.1002/hep.25532

8. Bartoletti M, Giannella M, Lewis RE, Viale P. Bloodstream infections in patients with liver cirrhosis. Virulence. 2016;7:309–19. https://doi.org/10.1080/21505594.2016.1141162

9. Bartoletti M, Giannella M, Caraceni P, Domenicali M, Ambretti S, Tedeschi S, et al. Epidemiology and outcomes of bloodstream infection in patients with cirrhosis. J Hepatol. 2014;61:51–8. https://doi.org/10.1016/j.jhep.2014.03.021

10. Xie Y, Tu B, Xu Z, Xin Z, Bi J, Zhao M, et al. Bacterial distributions and prognosis of bloodstream infections in patients with liver cirrhosis. Sci Rep. 2017;7:1–9. https://doi.org/10.1038/s41598-017-11587-1

11. Johnson AL, Ratnasekera IU, Irvine KM, Henderson A, Powell EE, Valery PC. Bacteraemia, sepsis and antibiotic resistance in Australian patients with cirrhosis: a population-based study. BMJ Open Gastroenterol 2021;Dec;8(1):1–12. https://doi.org/10.1136/bmj gast-2021-000695

12. White K, Tabah A, Ramanan M, Shekar K, Edwards F, Laupland KB. 90-day case-fatality in critically ill patients with chronic liver Disease Influenced by Presence of Portal Hypertension, results from a Multicentre Retrospective Cohort Study. J Intensive Care Med. 2023;38:5–10. https://doi.org/10.1177/08850666221100408

13. Brandolini M, Corbella M, De Silvestri A, Tinelli C, Albonico G, Albertini R, et al. Epidemiological characteristics of bloodstream infections in patients with different degrees of liver disease. Infection. 2015;43:561–7. https://doi.org/10.1007/s15010-015-0794-6

14. Westphal J, Jehl F, Vetter D, Pharmacological. Toxicologic, and Microbiological considerations in the choice of initial antibiotic therapy for serious infections in patients with cirrhosis of the liver. Clin Infect Dis 1994;324–35.

15. Bartoletti M, Giannella M, Lewis R, Caraceni P, Tedeschi S, Paul M, et al. A prospective multicentre study of the epidemiology and outcomes of bloodstream infection in cirrhotic patients. Clin Microbiol Infect. 2018;24:4–11. https://doi.org/10.1016/j.cmi.2017.08.001

16. Kim M, Cardoso FS, Pawlowski A, Wunderink R, Ladner DP, Abraldes JG, et al. The impact of multidrug-resistant microorganisms on critically ill patients with cirrhosis in the intensive care unit: a cohort study. Hepatol Commun. 2023;7:e0038–0038. https://doi.org/10.1097/hc9.0000000000000038

17. Dong Y, Sun D, Wang Y, Du Q, Zhang Y, Han R, et al. Evaluation of the current guidelines for antibacterial therapy strategies in patients with cirrhosis or liver failure. BMC Infect Dis. 2022;22:1–14. https://doi.org/10.1186/s12879-021-07018-2

18. Angeli P, Bernardi M, Villanueva C, Francoz C, Mookerjee RP, Trebicka J, et al. EASL Clinical Practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406–60. https://doi.org/10.1016/j.jhep.2018.03.024

19. Hoenigl M, Wagner J, Raggam RB, Rueller F, Prattes J, Eigl S, et al. Characteristics of hospital-acquired and community-onset blood stream infections, South-East Austria. PLoS ONE. 2014;9:4–9. https://doi.org/10.1371/journal.pone.0104702

20. Buetti N, Tabah A, Loiodice A, Ruckly S, Aslan AT. Different epidemiology of bloodstream infections in COVID – 19 compared to non – COVID – 19 critically ill patients: a descriptive analysis of the Eurobact II study. Crit Care. 2022;18:1–12. https://doi.org/10.1186/s13054-022-04166-y

21. Gharaibeh A, Koppikar S, Bonilla-Escobar J. Strengthening the reporting of Observational studies in Epidemiology (STROBE) in the International Journal of Medical Students. Int J Med Students. 2014;2:36–7. https://doi.org/10.5195/ijms.2014.76

22. Charlson ME, Pompei P, Ales KLMC. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.

23. Uda A, Shigemura K, Kitagawa K, Osawa K, Onuma K, Yan Y, et al. Risk factors for the acquisition of enterococcus faecium infection and mortality in patients with enterococcal bacteremia: a 5-year retrospective analysis in a tertiary care university hospital. Antibiotics. 2021;10:1–11. https://doi.org/10.3390/antibiotics10010064

24. Billington EO, Phang SH, Gregson DB, Pitout JDD, Ross T, Church DL, et al. Incidence, risk factors, and outcomes for Enterococcus spp. blood stream infections: a population-based study. Int J Infect Dis. 2014;26. https://doi.org/10.1016/j.ijid.2014.02.012

25. Buetti N, Marschall J, Timsit JF, Atkinson A, Kronenberg A, Sommerstein R, et al. Distribution of pathogens and antimicrobial resistance in bacteraemia according to hospitalization duration: a nationwide surveillance study in Switzerland. Clin Microbiol Infect. 2021;27:1820–5. https://doi.org/10.1016/j.cmi.2021.04.025

26. Cressman AM, MacFadden DR, Verma AA, Razak FDN. Empiric antibiotic treatment thresholds for serious bacterial infections: a scenario-based Survey Study. Clin Infect Dis. 2019;2019:1–24.

27. Morvan AC, Henry B, Garroute-Orgeas M, Ruckly S, Forel JM, Argaud L, et al. Impact of species and antibiotic therapy of enterococcal peritonitis on 30-day mortality in critical care - an analysis of the OUTCOMEREA database. Crit Care. 2019;23:1–10. https://doi.org/10.1186/s13054-019-2581-8

28. Theocharidou E, Agarwal B, Jeffrey G, Jalan R, Harrison D, Burroughs AK, et al. Early invasive fungal infections and colonization in patients with cirrhosis admitted to the intensive care unit. Clin Microbiol Infect. 2016;22. https://doi.org/10.1016/j.cmi.2015.10.020.:189.e1-189.e7.

29. Rasool S, Babar AN, Shafquat U, Azhar S, Khan RR. Fungal infections in patients with chronic liver disease: mortality and associated risk factors. Int J Res Med Sci. 2019;7:3882. https://doi.org/10.18203/2320-6012.ijrms20194326

30. Bajaj JS, Leary JGO, Tandon P, Wong F, Garcia-tsao G, Kamath PS, et al. Outcomes in hospitalized patients with cirrhosis. Am J Infect Dis. 2020;3:1091–100. https://doi.org/10.14309/ajg.0000000000000280.Nosocomial

31. Vincent JL. Nosocomial infections in adult intensive-care units. Lancet. 2003;361:2068–77. https://doi.org/10.1016/S0140-6736(03)13644-6

## Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
## References

1. Tabah A, Koulenti D, Laupland K, Misset B, Valles J, Bruzzi De Carvalho F, et al. Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med. 2012;38:1930-45. https://doi.org/10.1007/s00134-012-2695-9

2. Tabah A, Buetti N, Staiquly Q, Ruckly S, Akova M, Aslan AT, et al. Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study. Intensive Care Med. 2023;49:178-90. https://doi.org/10.1007/s00134-022-06944-2

3. Merli M, Lucidi C, Giannelli V, Giusto M, Riggio O, Falcone M, et al. Cirrhotic patients are at risk for health care-associated bacterial infections. Clin Gastroenterol Hepatol. 2010;8:979-e9851. https://doi.org/10.1016/j.cgh.2010.06.024

4. Bajaj JS, O'Leary JG, Tandon P, Wong F, Garcia-Tsao G, Kamath PS, Biggins SW, Lai JC, Vargas HE, Maliakkal B, Fallon MB, Thuluvath PJ, Subramanian RM, Thacker LRRK. Outcomes in hospitalized patients with nosocomial infections are frequent and negatively impact outcomes in hospitalized patients with cirrhosis. Am J Gastroenterol. 2019;3:1091-100. https://doi.org/10.14309/ajg.0000000000000280.Nosocomial

5. D'oliveira RAC, Pereira LCD, Codes L, Rocha M, de Bittencourt S. Analysis of healthcare associated and hospital acquired infections in critically ill patients with cirrhosis. Arq Gastroenterol. 2022;59:102-9. https://doi.org/10.1590/S0004-2803.202200001-8

6. Bunchorntavakul C, Chamroonkul N, Chavalitdhamrong D. Bacterial infections in cirrhosis: a critical review and practical guidance. World J Hepatol. 2016;8:307-21. https://doi.org/10.4254/wjh.v8.i6.307

7. Fernández J, Acevedo J, Castro M, García O, Rodríguez de Lope C, Roca D, et al. Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study. Hepatology. 2012;55:1551-61. https://doi.org/10.1002/hep.25532

8. Bartoletti M, Giannella M, Lewis RE, Viale P. Bloodstream infections in patients with liver cirrhosis. Virulence. 2016;7:309-19. https://doi.org/10.1080/21505594.2016.1141162

9. Bartoletti M, Giannella M, Caraceni P, Domenicali M, Ambretti S, Tedeschi S, et al. Epidemiology and outcomes of bloodstream infection in patients with cirrhosis. J Hepatol. 2014;61:51-8. https://doi.org/10.1016/j.jhep.2014.03.021

10. Xie Y, Tu B, Xu Z, Xin Z, Bi J, Zhao M, et al. Bacterial distributions and prognosis of bloodstream infections in patients with liver cirrhosis. Sci Rep. 2017;7:1-9. https://doi.org/10.1038/s41598-017-11587-1

11. Johnson AL, Ratnasekera IU, Irvine KM, Henderson A, Powell EE, Valery PC. Bacteraemia, sepsis and antibiotic resistance in Australian patients with cirrhosis: a population-based study. BMJ Open Gastroenterol 2021;Dec;8(1):1-12. https://doi.org/10.1136/bmjgast-2021-000695

12. White K, Tabah A, Ramanan M, Shekar K, Edwards F, Laupland KB. 90-day case-fatality in critically ill patients with chronic liver Disease Influenced by Presence of Portal Hypertension, results from a Multicentre Retrospective Cohort Study. J Intensive Care Med. 2023;38:5-10. https://doi.org/10.1177/08850666221100408

13. Brandolini M, Corbella M, De Silvestri A, Tinelli C, Albonico G, Albertini R, et al. Epidemiological characteristics of bloodstream infections in patients with different degrees of liver disease. Infection. 2015;43:561-7. https://doi.org/10.1007/s15010-015-0794-6

14. Westphal J, Jehl F, Vetter D, Pharmacological. Toxicologic, and Microbiological considerations in the choice of initial antibiotic therapy for serious infections in patients with cirrhosis of the liver. Clin Infect Dis 1994;324-35.

15. Bartoletti M, Giannella M, Lewis R, Caraceni P, Tedeschi S, Paul M, et al. A prospective multicentre study of the epidemiology and outcomes of bloodstream infection in cirrhotic patients. Clin Microbiol Infect. 2018;24:4-11. https://doi.org/10.1016/j.cmi.2017.08.001

16. Kim M, Cardoso FS, Pawlowski A, Wunderink R, Ladner DP, Abraldes JG, et al. The impact of multidrug-resistant microorganisms on critically ill patients with cirrhosis in the intensive care unit: a cohort study. Hepatol Commun. 2023;7:e0038-0038. https://doi.org/10.1097/hc9.0000000000000038

17. Dong Y, Sun D, Wang Y, Du Q, Zhang Y, Han R, et al. Evaluation of the current guidelines for antibacterial therapy strategies in patients with cirrhosis or liver failure. BMC Infect Dis. 2022;22:1-14. https://doi.org/10.1186/s12879-021-07018-2

18. Angeli P, Bernardi M, Villanueva C, Francoz C, Mookerjee RP, Trebicka J, et al. EASL Clinical Practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406-60. https://doi.org/10.1016/j.jhep.2018.03.024

19. Hoenigl M, Wagner J, Raggam RB, Rueller F, Prattes J, Eigl S, et al. Characteristics of hospital-acquired and community-onset blood stream infections, South-East Austria. PLoS ONE. 2014;9:4-9. https://doi.org/10.1371/journal.pone.0104702

20. Buetti N, Tabah A, Loiodice A, Ruckly S, Aslan AT. Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study. Crit Care. 2022;18:1-12. https://doi.org/10.1186/s13054-022-04166-y

21. Gharaibeh A, Koppikar S, Bonilla-Escobar J. Strengthening the reporting of Observational studies in Epidemiology (STROBE) in the International Journal of Medical Students. Int J Med Students. 2014;2:36-7. https://doi.org/10.5195/ijms.2014.76

22. Charlson ME, Pompei P, Ales KLMC. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373-83.

23. Uda A, Shigemura K, Kitagawa K, Osawa K, Onuma K, Yan Y, et al. Risk factors for the acquisition of enterococcus faecium infection and mortality in patients with enterococcal bacteremia: a 5-year retrospective analysis in a tertiary care university hospital. Antibiotics. 2021;10:1-11. https://doi.org/10.3390/antibiotics10010064

24. Billington EO, Phang SH, Gregson DB, Pitout JDD, Ross T, Church DL, et al. Incidence, risk factors, and outcomes for Enterococcus spp. blood stream infections: a population-based study. Int J Infect Dis. 2014;26. https://doi.org/10.1016/j.ijid.2014.02.012

25. Buetti N, Marschall J, Timsit JF, Atkinson A, Kronenberg A, Sommerstein R, et al. Distribution of pathogens and antimicrobial resistance in bacteraemia according to hospitalization duration: a nationwide surveillance study in Switzerland. Clin Microbiol Infect. 2021;27:1820-5. https://doi.org/10.1016/j.cmi.2021.04.025

26. Cressman AM, MacFadden DR, Verma AA, Razak FDN. Empiric antibiotic treatment thresholds for serious bacterial infections: a scenario-based Survey Study. Clin Infect Dis. 2019;2019:1-24.

27. Morvan AC, Henry B, Garroute-Orgeas M, Ruckly S, Forel JM, Argaud L, et al. Impact of species and antibiotic therapy of enterococcal peritonitis on 30-day mortality in critical care - an analysis of the OUTCOMEREA database. Crit Care. 2019;23:1-10. https://doi.org/10.1186/s13054-019-2581-8

28. Theocharidou E, Agarwal B, Jeffrey G, Jalan R, Harrison D, Burroughs AK, et al. Early invasive fungal infections and colonization in patients with cirrhosis admitted to the intensive care unit. Clin Microbiol Infect. 2016;22. https://doi.org/10.1016/j.cmi.2015.10.020.:189.e1-189.e7.

29. Rasool S, Babar AN, Shafquat U, Azhar S, Khan RR. Fungal infections in patients with chronic liver disease: mortality and associated risk factors. Int J Res Med Sci. 2019;7:3882. https://doi.org/10.18203/2320-6012.ijrms20194326

30. Bajaj JS, Leary JGO, Tandon P, Wong F, Garcia-tsao G, Kamath PS, et al. Outcomes in hospitalized patients with cirrhosis. Am J Infect Dis. 2020;3:1091-100. https://doi.org/10.14309/ajg.0000000000000280.Nosocomial

31. Vincent JL. Nosocomial infections in adult intensive-care units. Lancet. 2003;361:2068-77. https://doi.org/10.1016/S0140-6736(03)13644-6

## Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.