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

Niccolò Buetti, Alexis Tabah, Nour Setti, Stéphane Ruckly, François Barbier, Murat Akova, Abdullah Tarik Aslan, Marc Leone, Matteo Bassetti, Andrew Conway Morris, et al.

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## To cite this version:

Niccolò Buetti, Alexis Tabah, Nour Setti, Stéphane Ruckly, François Barbier, et al.. The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections. Intensive Care Medicine, 2024, 50 (6), pp.873-889. 10.1007/s00134-024-07348-0. inserm-04635796

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

Niccolò Buetti<fnref n="1" />,²* , Alexis Tabah³,⁴,⁵,⁶, Nour Setti², Stéphane Ruckly²,³¹, François Barbier⁷,⁸, Murat Akova⁹, Abdullah Tarik Aslan¹⁰,¹¹, Marc Leone¹², Matteo Bassetti¹³, Andrew Conway Morris¹⁴,¹⁵,¹⁶, Kostoula Arvaniti¹⁷, José-Artur Paiva¹⁸,¹⁹,²⁰, Ricard Ferrer²¹, Haibo Qiu²², Giorgia Montrucchio²³,²⁴, Andrea Cortegiani²⁵,²⁶, Bircan Kayaaslan²⁷, Liesbet De Bus²⁸,²⁹, Jan J. De Waele²⁸,²⁹ and Jean-François Timsit²,³⁰ on behalf of the EUROBACT-2 Study Group, the European Society of Intensive Care Medicine (ESICM), the European Society of Clinical Microbiology, the Infectious Diseases (ESCMID) Study Group for Infections in Critically Ill Patients (ESGCIP), and the OUTCOMEREA Network

© 2024 The Author(s)

**Abstract**

**Purpose:** The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI).

**Methods:** We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators.

**Results:** Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03–2.14] or within a few hours (OR 1.79, 95% CI 1.34–2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09–1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47–0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44–1.00) or within a few hours (OR 0.51, 95% CI 0.37–0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47–0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00–2.80), and decreasing HDI values were associated with 28-day mortality.

<footnote>*Correspondence: niccolo.buetti@gmail.com</footnote>

<footnote n="1">¹ Infection Control Program, Geneva University Hospitals and Faculty of Medicine, World Health Organization Collaborating Centre, Geneva, Switzerland</footnote>

<footnote>Full author information is available at the end of the article</footnote>
**Conclusion:** Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.

**Keywords:** Hospital-acquired bloodstream infections, Bacteraemia, Centre, Process indicator, Outcome indicator

**Introduction**

Hospital-acquired bloodstream infections (HABSI) are one of the hospital-acquired infections with the highest health burden measured in disability-adjusted life years [1, 2]. HABSI are frequently observed in the intensive care unit (ICU) setting and are associated with high morbidity, and increased hospital costs and length of stay. To investigate HABSI, initial adequate therapy and mortality represent one of the most important process and outcome indicators [3–5]. Interestingly, international cohorts investigating indicators focussed mostly on individual patient factors [6, 7]. Due to the difficulty to perform large multicentre cohorts, the role of centre-/country-based factors has been widely disregarded in the literature. Several surveys or international surveillance systems showed that the structure of the ICU and microbiological laboratory as well as epidemiological resistance data may substantially differ between different centres and countries [8–11]. However, associations between these structural indicators and the adequacy of antimicrobial therapy or mortality remain unknown due to the paucity of standardised data globally.

From 2019 to 2021, we conducted the EUROBACT-2 study, a prospective cohort that was designed to update the epidemiology and main factors associated with mortality in ICU patients with HABSI from ICUs worldwide [12]. We sought to use data from this high-quality cohort to evaluate the associations between centre-/country-based factors and two important process and outcome indicators, the adequacy of antimicrobial therapy within the first 24 h, and the 28-day mortality, respectively.

**Material and methods**

**EUROBACT-2 study design**

The EUROBACT-2 was a prospective multicontinental cohort study performed between September 2019 and June 2021 [12]. This clinical study was registered within ClinicalTrials.org (NCT03937245) and the results are reported in accordance with the STrengthening the Reporting of OBservational studies in Epidemiology guidelines [13].

**Setting**

Endorsement, logistic, and financial support was obtained from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP) and the

**Take-home message**

The role of different structural indicators or centre-/country-based factors has been widely disregarded in the literature
Therapeutic drug monitoring strategies, availability of clinical pharmacists, weekly screening for multidrug-resistant microorganism carriage, vancomycin-resistant enterococci prevalence in hospital-acquired bloodstream infections, and Human Development Index could be associated with adequacy of antimicrobial therapy and mortality

European Society of Intensive Care Medicine (ESICM). An operational committee (AT, JFT, FB, SR, and NB) oversaw all study operations. National coordinators (NCs) recruited participating centres, applied for regulatory and ethical approvals, and facilitated communication within different countries.

**Centres and patients**

The included centres were ICUs, defined as a unit specifically designed to manage patients with organ failure within an hospital and able to provide invasive mechanical ventilation for at least 24 h. The EUROBACT-2 study recruited centres with patients with HABSI from 1st June 2019 to 30th January 2021. For this specific analysis, amongst all EUROBACT-2 participating centres, we selected those that included a minimum of ten consecutive HABSI patients or those that recruited patients for a period > 2 months. A flexible start of the inclusion period was allowed for each centre to facilitate participation in the cohort.

Adult patients (≥ 18 years old) with a first episode of HABSI treated in ICU were enrolled. A HABSI was defined as a positive blood culture sampled 48 h after hospital admission. Treatment in the ICU was defined as either the blood culture having been sampled in the ICU or the patient having been transferred to the ICU (i.e. in 48 h) for the treatment of the HABSI.

**Data collection, definitions, and indicators**

*Hospital, centre (ICU), and country data.*

Data on hospital and centre characteristics were stratified into the following subgroups: (1) structure of the ICU (i.e. variables that described type of ICU, personal, [infra]structure and organisation), (2) organisation of the microbiology laboratory (i.e. microbiological processing and reporting) and infectious diseases (i.e. variables that
described availability of specialists, therapy drug monitoring [TDM] and institutional policy about treatments) and (3) aggregated ICU antimicrobial resistance (AMR)-related factors (i.e. variables that described or could influence AMR). We also collected data from countries of each of the included centres (e.g. geographical, life expectancy, education and income data). We extracted Human Development Index [HDI] data which is composite index of life expectancy, education and per capita income indicators [14, 15]. Further, country data from WHO Tripartite AMR Country Self-Assessment Survey [TrACSS] were also extracted [16, 17].

*Individual patient data and outcomes.*

We collected patient data from the hospital charts and no additional tests or interventions were performed. Our primary process indicator was adequate antimicrobial therapy within the first 24 h after HABSI. It was defined as a therapy with at least one antimicrobial with in vitro activity for the microorganism at the first day, with adequacy of antimicrobial selection, dosing and administration manually reviewed for all infections and sources of HABSI by three experts (NB, AT and FB). Antimicrobials administered at ineffective or very low dose and/or route of administration, relative to the source of infection, were considered as not adequate.

Our primary outcome indicator was 28-day mortality. Patients were followed for up to 28 days or until hospital discharge and vital status was assessed on day 28.

**Statistical analyses**

Continuous variables were expressed as medians (interquartile range [IQR]) and categorical variables as absolute frequencies and percentages.

The statistical plan consisted of two steps. First, we described the differences in adequacy of antimicrobial therapy within the first 24 h and 28-day mortality using Chi-square (or Fisher) and Student *T* (or Wilcoxon) tests for categorical and numeric variables, respectively, for the following subgroups: (1) structure of the ICU, (2) organisation of the microbiology laboratory and infectious diseases, (3) aggregated ICU AMR-related factors and (4) country factors. Second, to identify factors associated with adequate antimicrobial therapy in the first 24 h or day-28 mortality, we built a two-tiered hierarchical logistic mixed model using the GLIMMIX procedure of the SAS software for each subgroup. The effects of centre-based variables were included as random intercepts. Multilevel modelling considered the hierarchical structure of the data, which may manifest as intraclass correlations. We performed mixed univariable and

multivariable logistic models for each subgroup. All non-colinear clinically relevant variables with *p* values < 0.10 by univariate analysis were introduced into the multivariable model. A backward process was then used for further variable selection. To mitigate bias introduced by severity of patients at the time of HABSI diagnosis, we forced in our multivariable models the variable “presence of septic shock” at the individual level. Moreover, we performed sensitivity analysis excluding centres that recruited patients affected by coronavirus disease 2029 (COVID-19).

Further details on skin contaminants, centre/country or individual patient variables, data quality, definitions, missing data and statistical analyses are described in the electronic supplementary material (ESM).

**Results**

**Participating ICUs and patients**

Amongst the 333 ICUs included in the EUROBACT-2 cohort, we excluded 132 ICUs that included less than 10 patients or for a period < 3 months (eFigure 1), leaving 201 ICUs from 47 countries eligible for the study (eFigure 2). Half of them were located in Europe (n=105, 52%) and two thirds were in Organization for Economic Cooperation and Development (OECD) member countries (n=137, 68%).

We included 2209 patients with a HABSI. Most patients were male (n=1388, 63%) with a median age of 64 (IQR 52; 73) years. The most common admission diagnoses were respiratory diseases (n=472, 21%) and sepsis or septic shock (n=427, 19%). Most HABSI (n=1766, 80%) were acquired in ICU.

Overall, 51% (n=1128) of patients received an adequate antimicrobial therapy within the first 24 h and 38% (n=839) died in-hospital within 28 days.

**Structure of the ICU**

In descriptive analyses, patients recruited from teaching hospitals received less frequently adequate antimicrobial therapy within the first 24 h, whereas patients recruited from burn units and in ICUs with higher number of senior doctors received more frequently adequate antimicrobial therapy within the first 24 h (Table 1). However, when univariable and multivariable mixed logistic models were used, these variables were not associated with adequate therapy within the first 24 h (eTable 1).

In descriptive analyses, type of ICU, number of beds per doctor, number of senior doctors, number of beds in the ICU, number of ventilator and non-ventilator beds in the ICU, and recruitment from general and paediatric wards were associated with increased 28-day mortality (Table 1). Using multivariable mixed logistic models with adjustment
<table><caption>Table 1 Structure of the ICU</caption><thead><tr><th></th><th>All centres (n = 201)</th><th>All patients (n = 2209)</th><th>No adequate treatment (n = 1081)</th><th>24-h adequate treatment (n = 1128)</th><th>p value</th><th>Alive or discharge alive at day-28 (n = 1370)</th><th>28-day mortality (n = 839)</th><th>p value</th></tr></thead><tbody><tr><td>Teaching hospital</td><td>168 (83.6)</td><td>1885 (85.3)</td><td>941 (87)</td><td>944 (83.7)</td><td>0.03</td><td>1168 (85.3)</td><td>717 (85.5)</td><td>0.90</td></tr><tr><td><strong>Funding</strong></td><td></td><td></td><td></td><td></td><td>0.88</td><td></td><td></td><td>0.59</td></tr><tr><td>Public</td><td>171 (85.1)</td><td>1888 (85.5)</td><td>928 (85.8)</td><td>960 (85.1)</td><td></td><td>1179 (86.1)</td><td>709 (84.5)</td><td></td></tr><tr><td>Private</td><td>10 (5)</td><td>101 (4.6)</td><td>48 (4.4)</td><td>53 (4.7)</td><td></td><td>61 (4.5)</td><td>40 (4.8)</td><td></td></tr><tr><td>Mixed</td><td>20 (10)</td><td>220 (10)</td><td>105 (9.7)</td><td>115 (10.2)</td><td></td><td>130 (9.5)</td><td>90 (10.7)</td><td></td></tr><tr><td><strong>Type of ICU</strong></td><td></td><td></td><td></td><td></td><td>0.42</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>Medical</td><td>165 (82.1)</td><td>1772 (80.2)</td><td>879 (81.3)</td><td>893 (79.2)</td><td></td><td>1127 (82.3)</td><td>645 (76.9)</td><td></td></tr><tr><td>Surgical</td><td>13 (6.5)</td><td>125 (5.7)</td><td>56 (5.2)</td><td>69 (6.1)</td><td></td><td>84 (6.1)</td><td>41 (4.9)</td><td></td></tr><tr><td>Mixed</td><td>23 (11.4)</td><td>312 (14.1)</td><td>146 (13.5)</td><td>166 (14.7)</td><td></td><td>159 (11.6)</td><td>153 (18.2)</td><td></td></tr><tr><td><strong>Structure of the ICU</strong></td><td></td><td></td><td></td><td></td><td>0.07</td><td></td><td></td><td>0.05</td></tr><tr><td>Closed ICU</td><td>156 (77.6)</td><td>1762 (79.8)</td><td>845 (78.2)</td><td>917 (81.3)</td><td></td><td>1111 (81.1)</td><td>651 (77.6)</td><td></td></tr><tr><td>Open ICU</td><td>45 (22.4)</td><td>447 (20.2)</td><td>236 (21.8)</td><td>211 (18.7)</td><td></td><td>259 (18.9)</td><td>188 (22.4)</td><td></td></tr><tr><td>Number of beds per nurse (miss = 5)</td><td>2.1 [1.5; 2.9]</td><td>2.3 [1.6; 2.8]</td><td>2.3 [1.7; 2.8]</td><td>2.2 [1.6; 2.9]</td><td>0.33</td><td>2.3 [1.6; 2.9]</td><td>2.3 [1.7; 2.6]</td><td>0.47</td></tr><tr><td>Number of beds per doctor<sup>a</sup> (miss = 3)</td><td>3 [1.9; 4.1]</td><td>2.8 [1.9; 4.1]</td><td>3 [1.9; 4.5]</td><td>2.7 [1.8; 4]</td><td>0.10</td><td>3 [1.9; 4.2]</td><td>2.6 [1.8; 4]</td><td>0.02</td></tr><tr><td>Number of junior or in training doctors (miss = 4)</td><td>3 [2; 6]</td><td>3.5 [2.5; 5.5]</td><td>3 [2; 6]</td><td>4 [2; 5]</td><td>0.73</td><td>3 [2; 6]</td><td>4 [2; 5]</td><td>0.31</td></tr><tr><td>Number of senior doctors (miss = 4)</td><td>3 [2; 5]</td><td>3 [2; 5]</td><td>3 [2; 4]</td><td>3 [2; 5]</td><td>&lt;0.01</td><td>3 [2; 5]</td><td>3 [2; 4]</td><td>0.02</td></tr><tr><td>Number of ventilator equivalent beds in the ICU (miss = 1)</td><td>15 [10; 22.5]</td><td>15 [11; 23]</td><td>15 [11; 24]</td><td>15 [11; 22]</td><td>0.34</td><td>15 [11; 24]</td><td>14 [11; 22]</td><td>&lt;0.01</td></tr><tr><td>Presence of intermediate care beds (miss = 1)</td><td>103 (51.5)</td><td>982 (44.6)</td><td>463 (42.9)</td><td>519 (46.2)</td><td>0.12</td><td>662 (48.5)</td><td>320 (38.2)</td><td>&lt;0.01</td></tr><tr><td>Number of beds in the ICU (miss = 1)</td><td>20 [12; 28.5]</td><td>20 [12; 28]</td><td>20 [12; 28]</td><td>20 [12; 28]</td><td>0.69</td><td>21 [13; 30]</td><td>18 [12; 27]</td><td>&lt;0.01</td></tr><tr><td>Recruitment: general or paediatric wards</td><td>188 (93.5)</td><td>2093 (94.7)</td><td>1033 (95.6)</td><td>1060 (94)</td><td>0.09</td><td>1285 (93.8)</td><td>808 (96.3)</td><td>0.01</td></tr><tr><td>Recruitment: cardiac surgery, coronary care or post-operative, neuro-surgical or trauma wards</td><td>162 (80.6)</td><td>1782 (80.7)</td><td>865 (80)</td><td>917 (81.3)</td><td>0.45</td><td>1124 (82)</td><td>658 (78.4)</td><td>0.04</td></tr><tr><td>Recruitment: burn wards</td><td>40 (19.9)</td><td>358 (16.2)</td><td>157 (14.5)</td><td>201 (17.8)</td><td>0.04</td><td>233 (17)</td><td>125 (14.9)</td><td>0.19</td></tr><tr><td>24-h medical coverage by senior level doctors</td><td>188 (93.5)</td><td>2021 (91.5)</td><td>977 (90.4)</td><td>1044 (92.6)</td><td>0.07</td><td>1262 (92.1)</td><td>759 (90.5)</td><td>0.18</td></tr><tr><td>24-h medical coverage by junior or in training doctors</td><td>171 (85.1)</td><td>1904 (86.2)</td><td>925 (85.6)</td><td>979 (86.8)</td><td>0.41</td><td>1190 (86.9)</td><td>714 (85.1)</td><td>0.24</td></tr><tr><td>General surgery team and operating theatre available 24/7</td><td>199 (99)</td><td>2196 (99.4)</td><td>1074 (99.4)</td><td>1122 (99.5)</td><td>0.72</td><td>1366 (99.7)</td><td>830 (98.9)</td><td>0.04</td></tr></tbody></table>

ICU intensive Care Unit, Miss missing data. Of note, missing data are counted at centre level in this table

a Number of doctor included senior and junior doctors for this ratio
Adequate antimicrobial therapy within the first 24 hours

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

28-day mortality

<figure><img src="image_5.png" /><figcaption>**Fig. 1** Multivariable mixed logistical models for adequate antimicrobial therapy within the first 24 h and 28-day mortality. The first panel relates to adequate antimicrobial therapy within the first 24 h, the second panel 28-day mortality. **ICU** intensive care unit, **OR** odds ratio, **CI** confidence interval, **TDM** therapeutic drug monitoring, **AMR** antimicrobial resistance</figcaption></figure>
for the presence of septic shock, the availability of interme-
diate care beds in the ICU was associated with decreased
28-day mortality (odds ratio [OR] 0.63, 95% confidence
interval [CI] 0.47–0.84, *p* = 0.0017, Fig. 1, eTable 2).

## Organisation of the microbiology laboratory and infectious diseases

Having an infectious diseases (ID) specialist in the
ICU, scheduled ID rounds or multidisciplinary meet-
ings with ID specialists, the presence of a clinical phar-
macist as part of the permanent ICU staff, empirical
antibiotic treatment determined by local infection treat-
ment guidelines, TDM for aminoglycosides, vancomycin
and beta-lactam, automated blood culture incubation,
monitoring for positive blood cultures every 24 h and
7 days a week, and performing molecular tests in case
of multidrug-resistant bacteria were associated with an
increased percentage of adequate therapy within the first
24 h (Table 2). Using multivariable mixed logistic mod-
els with adjustment for the presence of septic shock,
only TDM for aminoglycosides was associated with an
increased probability of adequate therapy within the first
24 h (TDM available at least once a week, OR 1.22 [95%
CI 0.76–1.95]; TDM available every day, OR 1.48 [95%
CI 1.03–2.14]; TDM available every day within a few hours,
OR 1.79 [95% CI 1.34–2.38]; *p* < 0.01, Fig. 1, eTable 3).

Scheduled ID rounds or multidisciplinary meetings, fre-
quent consultation with clinical pharmacists, the presence
of a clinical pharmacist as part of the permanent ICU staff,
empirical antibiotic treatment determined by national/inter-
national or local guidelines, collection of microbiological
surgical site or procedural site specimens, TDM for amino-
glycosides, vancomycin and beta-lactam, results of positive
blood culture reported on personal contact and 24/7, anti-
biotic susceptibility test directly performed from the posi-
tive blood culture, and molecular test performed in case of
multidrug-resistant bacteria were associated with decreased
28-day mortality. Using multivariable mixed logistic models
with adjustment for the presence of septic shock, TDM for
aminoglycosides was associated with decreased probability
of 28-day mortality (TDM available at least once a week, OR
0.81 [95% CI 0.48–1.36]; TDM available every day, OR 0.66
[95% CI 0.44–1.00]; TDM available every day within a few
hours, OR 0.51 [95% CI 0.37–0.70]; *p* < 0.01, Fig. 1, eTable 4).
Moreover, consultation of clinical pharmacists was associ-
ated with decreased 28-day mortality (24/7 consultation,
OR 0.67 [95% CI 0.47–0.95]; business hours consultation,
OR 0.75 [95% CI 0.53–1.06]).

ICU AMR-related factors

Selective oropharyngeal and/or digestive tract decon-
tamination, surveillance cultures and screening for multi-
drug-resistant organism carriage, different percentage of
vancomycin-resistant enterococci (VRE) and extended-
spectrum beta-lactamase (ESBL)-producing Enterobac-
terales were associated with adequate therapy within the
first 24 h (Table 3). Using multivariable mixed logistic
models with adjustment for the presence of septic shock,
surveillance cultures and screening for multidrug-resistant
organism carriage were associated with an increased prob-
ability of adequate therapy within the first 24 h (screening
for all patients on admission, OR 1.07 [95% CI 0.75–1.53];
screening for all patients on admission and at least once
weekly, OR 1.45 [95% CI 1.09–1.93]; Fig. 1, eTable 5).

Surveillance cultures and screening for multidrug-
resistant organism carriage, different percentage of
methicillin-resistant *Staphylococcus aureus* (MRSA),
VRE, ESBL-producing Enterobacterales and carbap-
enemase-producing Enterobacterales were associated
with 28-day mortality (Table 3). Using multivariable
mixed logistic models with adjustment for the pres-
ence of septic shock, percentage of VRE between 10
and 25% was associated with increased 28-day mortal-
ity (OR 1.67 [95% CI 1.00–2.80], Fig. 1, eTable 6).

Country factors

Median values of HDI and current health expenditure were increased in patients who received an adequate therapy within the first 24 h. Moreover, patients recruited in countries with training and professional education on AMR, in countries with data on reports from national surveillance system for AMR, and in countries with policies for optimising antimicrobial use implemented in most healthcare facilities had higher proportions of adequate therapy within the first 24 h (Table 4). Using multivariable mixed logistic models with adjustment for the presence of septic shock, increasing HDI values were associated with increased OR for adequate therapy within the first 24 h (Fig. 1, eTable 7).

Median values of HDI and current health expendi-
ture were decreased in patients who died within
28 days (Table 4). Moreover, patients recruited in
countries with training and professional education
on AMR, in countries with data reports from national
surveillance system for AMR and with policies for
optimising antimicrobial use implemented in most
healthcare facilities were associated with decreased
28-day mortality. Using multivariable mixed logistic
<table><caption>Table 2 Organisation of the microbiology laboratory and infectious diseases</caption><thead><tr><th></th><th>All centres (n=201)</th><th>All patients (n=2209)</th><th>No adequate treatment (n=1081)</th><th>24-h adequate treatment (n=1128)</th><th>p value</th><th>Alive or discharge alive at day-28 (n=1370)</th><th>28-day mortality (n=839)</th><th>p value</th></tr></thead><tbody><tr><td>Consultation of infectious diseases specialists or clinical microbiologists (miss = 28)</td><td></td><td></td><td></td><td></td><td>0.17</td><td></td><td></td><td>0.12</td></tr><tr><td>24 h/7 days</td><td>103 (59.5)</td><td>1275 (66.8)</td><td>647 (68.8)</td><td>628 (64.8)</td><td></td><td>766 (65.1)</td><td>509 (69.3)</td><td></td></tr><tr><td>Business</td><td>58 (33.5)</td><td>540 (28.3)</td><td>248 (26.4)</td><td>292 (30.1)</td><td></td><td>345 (29.3)</td><td>195 (26.6)</td><td></td></tr><tr><td>Never</td><td>12 (6.9)</td><td>95 (5)</td><td>46 (4.9)</td><td>49 (5.1)</td><td></td><td>65 (5.5)</td><td>30 (4.1)</td><td></td></tr><tr><td>At least one ICU physician is an infectious diseases specialist</td><td>30 (14.9)</td><td>359 (16.3)</td><td>156 (14.4)</td><td>203 (18)</td><td>0.02</td><td>766 (65.1)</td><td>509 (69.3)</td><td>0.32</td></tr><tr><td>Scheduled infectious diseases rounds or multidisciplinary meetings</td><td>51 (25.4)</td><td>504 (22.8)</td><td>224 (20.7)</td><td>280 (24.8)</td><td>0.02</td><td>344 (25.1)</td><td>160 (19.1)</td><td>&lt;0.01</td></tr><tr><td>Consultation of clinical pharmacists (miss = 22)</td><td></td><td></td><td></td><td></td><td>0.33</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>24/7</td><td>56 (31.3)</td><td>578 (28.7)</td><td>270 (27.6)</td><td>308 (29.7)</td><td></td><td>402 (32.5)</td><td>176 (22.6)</td><td></td></tr><tr><td>Business hours</td><td>53 (29.6)</td><td>477 (23.7)</td><td>226 (23.1)</td><td>251 (24.2)</td><td></td><td>300 (24.3)</td><td>177 (22.8)</td><td></td></tr><tr><td>Never</td><td>70 (39.1)</td><td>960 (47.6)</td><td>483 (49.3)</td><td>477 (46)</td><td></td><td>535 (43.2)</td><td>425 (54.6)</td><td></td></tr><tr><td>Clinical pharmacists available as part of the permanent staff of the ICU</td><td>36 (17.9)</td><td>341 (15.4)</td><td>149 (13.8)</td><td>192 (17)</td><td>0.04</td><td>249 (18.2)</td><td>92 (11)</td><td>&lt;0.01</td></tr><tr><td>Clinical pharmacists in scheduled multidisciplinary staff meetings</td><td>17 (8.5)</td><td>168 (7.6)</td><td>72 (6.7)</td><td>96 (8.5)</td><td>0.10</td><td>109 (8)</td><td>59 (7)</td><td>0.43</td></tr><tr><td>Empirical antibiotic treatment determined by national/international infection treatment guidelines</td><td>123 (61.2)</td><td>1349 (61.1)</td><td>644 (59.6)</td><td>705 (62.5)</td><td>0.16</td><td>864 (63.1)</td><td>485 (57.8)</td><td>0.01</td></tr><tr><td>Empirical antibiotic treatment determined by local infection treatment guidelines</td><td>119 (59.2)</td><td>1193 (54)</td><td>540 (50)</td><td>653 (57.9)</td><td>&lt;0.01</td><td>790 (57.7)</td><td>403 (48)</td><td>&lt;0.01</td></tr><tr><td>Empirical antibiotic treatment determined by surveillance cultures</td><td>99 (49.3)</td><td>1140 (51.6)</td><td>541 (50)</td><td>599 (53.1)</td><td>0.15</td><td>707 (51.6)</td><td>433 (51.6)</td><td>0.99</td></tr><tr><td>Empirical antibiotic treatment determined by routine consultation of infectious diseases specialists, microbiologists, or clinical pharmacists</td><td>85 (42.3)</td><td>1085 (49.1)</td><td>550 (50.9)</td><td>535 (47.4)</td><td>0.11</td><td>643 (46.9)</td><td>442 (52.7)</td><td>&lt;0.01</td></tr><tr><td>Empirical antibiotic treatment determined by the treating physician</td><td>131 (65.2)</td><td>1365 (61.8)</td><td>651 (60.2)</td><td>714 (63.3)</td><td>0.14</td><td>888 (64.8)</td><td>477 (56.9)</td><td>&lt;0.01</td></tr><tr><td>When infection is suspected, surgical site or procedural site specimens are collected and sent for culture (miss = 1)</td><td></td><td></td><td></td><td></td><td>0.05</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>Never or only when requested by the treating physician</td><td>31 (15.5)</td><td>409 (18.6)</td><td>177 (16.5)</td><td>232 (20.6)</td><td></td><td>209 (15.3)</td><td>200 (23.9)</td><td></td></tr><tr><td>Most often</td><td>83 (41.5)</td><td>907 (41.2)</td><td>454 (42.3)</td><td>453 (40.2)</td><td></td><td>587 (43.1)</td><td>320 (38.2)</td><td></td></tr><tr><td>Always</td><td>86 (43)</td><td>883 (40.2)</td><td>442 (41.2)</td><td>441 (39.2)</td><td></td><td>566 (41.6)</td><td>317 (37.9)</td><td></td></tr><tr><td>TDM for aminoglycosides (miss = 1)</td><td></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td><td>&lt;0.01</td></tr></tbody></table>
<table><caption>Table 2 (continued)</caption><thead><tr><th></th><th>All centres (n = 201)</th><th>All patients (n = 2209)</th><th>No adequate treatment (n = 1081)</th><th>24-h adequate treatment (n = 1128)</th><th>p value</th><th>Alive or discharge alive at day-28 (n = 1370)</th><th>28-day mortality (n = 839)</th><th>p value</th></tr></thead><tbody><tr><td>Not available</td><td>71 (35.5)</td><td>962 (43.7)</td><td>530 (49.4)</td><td>432 (38.4)</td><td></td><td>525 (38.5)</td><td>437 (52.2)</td><td></td></tr><tr><td>Available at least once a week</td><td>17 (8.5)</td><td>175 (8)</td><td>91 (8.5)</td><td>84 (7.5)</td><td></td><td>103 (7.6)</td><td>72 (8.6)</td><td></td></tr><tr><td>Available every day within a few hours</td><td>78 (39)</td><td>740 (33.7)</td><td>306 (28.5)</td><td>434 (38.5)</td><td></td><td>517 (38)</td><td>223 (26.6)</td><td></td></tr><tr><td>Available every day</td><td>34 (17)</td><td>322 (14.6)</td><td>146 (13.6)</td><td>176 (15.6)</td><td></td><td>217 (15.9)</td><td>105 (12.5)</td><td></td></tr><tr><td>TDM for vancomycin (miss = 1)</td><td></td><td></td><td></td><td></td><td>&lt; 0.01</td><td></td><td></td><td>&lt; 0.01</td></tr><tr><td>Not available</td><td>51 (25.5)</td><td>758 (34.5)</td><td>405 (37.7)</td><td>353 (31.3)</td><td></td><td>418 (30.7)</td><td>340 (40.6)</td><td></td></tr><tr><td>Available at least once a week</td><td>22 (11)</td><td>246 (11.2)</td><td>140 (13)</td><td>106 (9.4)</td><td></td><td>148 (10.9)</td><td>98 (11.7)</td><td></td></tr><tr><td>Available every day within a few hours</td><td>88 (44)</td><td>842 (38.3)</td><td>363 (33.8)</td><td>479 (42.5)</td><td></td><td>554 (40.7)</td><td>288 (34.4)</td><td></td></tr><tr><td>Available every day</td><td>39 (19.5)</td><td>353 (16.1)</td><td>165 (15.4)</td><td>188 (16.7)</td><td></td><td>242 (17.8)</td><td>111 (13.3)</td><td></td></tr><tr><td>TDM for beta-lactams (miss = 1)</td><td></td><td></td><td></td><td></td><td>&lt; 0.01</td><td></td><td></td><td>&lt; 0.01</td></tr><tr><td>Not available</td><td>143 (71.5)</td><td>1630 (74.1)</td><td>830 (77.4)</td><td>800 (71)</td><td></td><td>972 (71.4)</td><td>658 (78.6)</td><td></td></tr><tr><td>Available at least once a week</td><td>33 (16.5)</td><td>345 (15.7)</td><td>134 (12.5)</td><td>211 (18.7)</td><td></td><td>242 (17.8)</td><td>103 (12.3)</td><td></td></tr><tr><td>Available every day within a few hours</td><td>8 (4)</td><td>84 (3.8)</td><td>47 (4.4)</td><td>37 (3.3)</td><td></td><td>56 (4.1)</td><td>28 (3.3)</td><td></td></tr><tr><td>Available every day</td><td>16 (8)</td><td>140 (6.4)</td><td>62 (5.8)</td><td>78 (6.9)</td><td></td><td>92 (6.8)</td><td>48 (5.7)</td><td></td></tr><tr><td>Blood cultures incubation started 24/7</td><td>149 (74.1)</td><td>1688 (76.4)</td><td>818 (75.7)</td><td>870 (77.1)</td><td>0.42</td><td>1025 (74.8)</td><td>663 (79)</td><td>0.02</td></tr><tr><td>Automated blood culture processing (miss = 1)</td><td>180 (90)</td><td>2003 (90.9)</td><td>965 (89.5)</td><td>1038 (92.2)</td><td>0.03</td><td>1232 (90.3)</td><td>771 (91.9)</td><td>0.19</td></tr><tr><td>Monitoring for positive blood cultures</td><td></td><td></td><td></td><td></td><td>&lt; 0.01</td><td></td><td></td><td>0.47</td></tr><tr><td>24/7</td><td>103 (51.2)</td><td>1186 (53.7)</td><td>553 (51.2)</td><td>633 (56.1)</td><td></td><td>743 (54.2)</td><td>443 (52.8)</td><td></td></tr><tr><td>Every day (including weekend), but not at night</td><td>77 (38.3)</td><td>790 (35.8)</td><td>392 (36.3)</td><td>398 (35.3)</td><td></td><td>491 (35.8)</td><td>299 (35.6)</td><td></td></tr><tr><td>During business hours of weekdays only (neither weekends nor nights)</td><td>21 (10.4)</td><td>233 (10.5)</td><td>136 (12.6)</td><td>97 (8.6)</td><td></td><td>136 (9.9)</td><td>97 (11.6)</td><td></td></tr><tr><td>Results of positive blood culture are reported 24/7 on personal contact</td><td>87 (43.3)</td><td>939 (42.5)</td><td>438 (40.5)</td><td>501 (44.4)</td><td>0.06</td><td>609 (44.5)</td><td>330 (39.3)</td><td>0.02</td></tr><tr><td>Perform of antibiotic susceptibility test (miss = 1)</td><td></td><td></td><td></td><td></td><td>0.04</td><td></td><td></td><td>&lt; 0.01</td></tr><tr><td>Directly from the positive blood culture (unless the direct smear examination shows different bacteria)</td><td>111 (55.5)</td><td>1142 (51.8)</td><td>535 (49.6)</td><td>607 (53.9)</td><td></td><td>738 (54.1)</td><td>404 (48.2)</td><td></td></tr><tr><td>From a sub-culture of the positive blood culture</td><td>89 (44.5)</td><td>1062 (48.2)</td><td>543 (50.4)</td><td>519 (46.1)</td><td></td><td>627 (45.9)</td><td>435 (51.8)</td><td></td></tr><tr><td>MIC not performed (miss = 6)</td><td>14 (7.2)</td><td>146 (6.7)</td><td>87 (8.2)</td><td>59 (5.3)</td><td></td><td>&lt; 0.01</td><td>66 (8)</td><td>0.06</td></tr><tr><td>In case of MDR bacteria phenotypic tests were performed</td><td>142 (70.6)</td><td>1484 (67.2)</td><td>713 (66)</td><td>771 (68.4)</td><td>0.23</td><td>954 (69.6)</td><td>530 (63.2)</td><td>&lt; 0.01</td></tr><tr><td>In case of MDR bacteria molecular tests were performed</td><td>76 (37.8)</td><td>854 (38.7)</td><td>391 (36.2)</td><td>463 (41)</td><td>0.02</td><td>562 (41)</td><td>292 (34.8)</td><td>&lt; 0.01</td></tr></tbody></table>
<table><caption>Table 2 (continued)</caption><thead><tr><th></th><th>All centres (n = 201)</th><th>All patients (n = 2209)</th><th>No adequate treatment (n = 1081)</th><th>24-h adequate treatment (n = 1128)</th><th>p value</th><th>Alive or discharge alive at day-28 (n = 1370)</th><th>28-day mortality (n = 839)</th><th>p value</th></tr></thead><tbody><tr><td>Results of susceptibility testing and the antibiogram are reported on electronic system</td><td>171 (85.1)</td><td>1951 (88.3)</td><td>958 (88.6)</td><td>993 (88)</td><td>0.67</td><td>1224 (89.3)</td><td>727 (86.7)</td><td>0.06</td></tr><tr><td>Susceptibility results are routinely provided by the laboratory as sensitive/resistant (without further detail)</td><td>134 (66.7)</td><td>1406 (63.6)</td><td>696 (64.4)</td><td>710 (62.9)</td><td>0.48</td><td>891 (65)</td><td>515 (61.4)</td><td>0.08</td></tr><tr><td>Susceptibility results are routinely provided by the laboratory as inhibition zones diameter with interpretation S/I/R</td><td>58 (28.9)</td><td>669 (30.3)</td><td>332 (30.7)</td><td>337 (29.9)</td><td>0.68</td><td>424 (30.9)</td><td>245 (29.2)</td><td>0.39</td></tr><tr><td>Susceptibility results are routinely provided by the laboratory as MIC data</td><td>132 (65.7)</td><td>1530 (69.3)</td><td>724 (67)</td><td>806 (71.5)</td><td>0.02</td><td>943 (68.8)</td><td>587 (70)</td><td>0.58</td></tr></tbody></table>

ICU intensive care unit, TDM therapeutic drug monitoring, MIC minimum inhibitory concentration, MDR multidrug resistance, S/I/R susceptible/intermediate/resistant, Miss missing data, of note, missing data are counted at centre level in this table

models with adjustment for the presence of septic shock, decreasing values of HDI were associated with increased 28-day mortality (Fig. 1, eTable 8).

## Sensitivity analysis excluding the centres that recruited COVID-19 patients

A sensitivity analysis excluding centres (n=59) that recruited COVID-19 patients (980 patients, 319 patients with COVID-19) during the study period showed similar results regarding the structure of the ICU factors, organisation of the microbiology laboratory and infectious diseases, ICU AMR-related and country factors for both indicators (eFigure 3).

## Discussion

Using a large international prospective cohort, we provided a detailed description of the organisation of ICUs, microbiology laboratories and antimicrobial stewardship processes worldwide. We showed that several factors related to the centre and country were associated with the adequacy of antimicrobial therapy and mortality in critically ill patients with HABSI. To our knowledge, such an in-depth analysis on centre- and country-specific factors has never been performed. Compared to the initial EUROBACT-2 publication [12], this analysis differs in the study population by including only the largest centres, centre-related factors were investigated in detail that were not investigated in the initial publication, including those relevant to the organisation of the microbiology laboratory, infectious diseases and AMR, as were country-level factors. Individual HABSI data were used only as adjustment factors, and this analysis provides an in-depth analysis of a process indicator (i.e. adequacy of antimicrobial therapy).

Indeed, cohort studies analysing adequacy of antimicrobial therapy or mortality have mostly focussed on individual risk factors [18, 19].

Aminoglycoside TDM was associated with an increased probability of adequate antimicrobial therapy within the first 24 h and with decreased mortality. TDM is frequently used to optimise exposure whilst minimising toxicity in antibiotics with complex pharmacokinetics or those with a narrow therapeutic window [20]. Aminoglycosides could lead to acute kidney injury due to acute tubular necrosis; therefore, pharmacokinetically monitored aminoglycoside therapy in critically ill patients may reduce toxicity [20]. In addition, aminoglycoside TDM could optimise antibiotic dosing in an attempt to achieve pharmacokinetic/pharmacodynamic targets and outcomes of severe infections in critically ill patients [20, 21]. It is, therefore, possible that the frequency of TDM may be associated with reduced mortality. However, TDM for aminoglycoside may simply
<table><caption>Table 3 Antimicrobial resistance-related factors in the ICU</caption><thead><tr><th></th><th>All centres (n=201)</th><th>All patients (n=2209)</th><th>No adequate treatment (n=1081)</th><th>24 h adequate treatment (n=1128)</th><th>p value</th><th>Alive or discharge alive at day-28 (n=1370)</th><th>28-day mortality (n=839)</th><th>p value</th></tr></thead><tbody><tr><td>Selective oropharyngeal and/or digestive tract decontamination (miss centre = 2)</td><td></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td><td>0.07</td></tr><tr><td>Never</td><td>134 (67.3)</td><td>1439 (66.1)</td><td>680 (64.1)</td><td>759 (68)</td><td></td><td>871 (64.3)</td><td>568 (69.1)</td><td></td></tr><tr><td>In a selected group of patients</td><td>25 (12.6)</td><td>266 (12.2)</td><td>121 (11.4)</td><td>145 (13)</td><td></td><td>174 (12.8)</td><td>92 (11.2)</td><td></td></tr><tr><td>In All ICU patients</td><td>40 (20.1)</td><td>472 (21.7)</td><td>260 (24.5)</td><td>212 (19)</td><td></td><td>310 (22.9)</td><td>162 (19.7)</td><td></td></tr><tr><td>Surveillance cultures and screening for multidrug-resistant organism carriage</td><td></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td><td>0.04</td></tr><tr><td>Never/only when clinically indicated</td><td>69 (34.3)</td><td>753 (34.1)</td><td>405 (37.5)</td><td>348 (30.9)</td><td></td><td>475 (34.7)</td><td>278 (33.1)</td><td></td></tr><tr><td>For all (most) patients, on admission</td><td>42 (20.9)</td><td>405 (18.3)</td><td>207 (19.1)</td><td>198 (17.6)</td><td></td><td>269 (19.6)</td><td>136 (16.2)</td><td></td></tr><tr><td>For all (most) patients, on admission and at least once weekly during the ICU stay</td><td>90 (44.8)</td><td>1051 (47.6)</td><td>469 (43.4)</td><td>582 (51.6)</td><td></td><td>626 (45.7)</td><td>425 (50.7)</td><td></td></tr><tr><td>Percentage of <i>Staphylococcus aureus</i> isolates resistant to methicillin in the ICU</td><td></td><td></td><td></td><td></td><td>0.27</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>Less than 10%</td><td>96 (47.8)</td><td>988 (44.7)</td><td>476 (44)</td><td>512 (45.4)</td><td></td><td>644 (47)</td><td>344 (41)</td><td></td></tr><tr><td>10 to 24.9%</td><td>40 (19.9)</td><td>456 (20.6)</td><td>225 (20.8)</td><td>231 (20.5)</td><td></td><td>282 (20.6)</td><td>174 (20.7)</td><td></td></tr><tr><td>25 to 100%</td><td>38 (18.9)</td><td>513 (23.2)</td><td>267 (24.7)</td><td>246 (21.8)</td><td></td><td>288 (21)</td><td>225 (26.8)</td><td></td></tr><tr><td>Unknown</td><td>27 (13.4)</td><td>252 (11.4)</td><td>113 (10.5)</td><td>139 (12.3)</td><td></td><td>156 (11.4)</td><td>96 (11.4)</td><td></td></tr><tr><td>Percentage of <i>Enterococcus</i> spp. isolates resistant to vancomycin in the ICU</td><td></td><td></td><td></td><td></td><td>0.04</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>Less than 10%</td><td>140 (69.7)</td><td>1496 (67.7)</td><td>757 (70)</td><td>739 (65.5)</td><td></td><td>961 (70.1)</td><td>535 (63.8)</td><td></td></tr><tr><td>10 to 24.9%</td><td>16 (8)</td><td>235 (10.6)</td><td>98 (9.1)</td><td>137 (12.1)</td><td></td><td>112 (8.2)</td><td>123 (14.7)</td><td></td></tr><tr><td>25 to 100%</td><td>16 (8)</td><td>128 (5.8)</td><td>66 (6.1)</td><td>62 (5.5)</td><td></td><td>87 (6.4)</td><td>41 (4.9)</td><td></td></tr><tr><td>Unknown</td><td>29 (14.4)</td><td>350 (15.8)</td><td>160 (14.8)</td><td>190 (16.8)</td><td></td><td>210 (15.3)</td><td>140 (16.7)</td><td></td></tr></tbody></table>
<table><caption>Table 3 (Continued)</caption><thead><tr><th></th><th>All centres<br>(n=201)</th><th>All patients<br>(n=2209)</th><th>No adequate treat-<br>ment (n=1081)</th><th>24 h adequate treat-<br>ment (n=1128)</th><th>p value</th><th>Alive or discharge<br>alive at day-28<br>(n=1370)</th><th>28-day mortality<br>(n=839)</th><th>p value</th></tr></thead><tbody><tr><td>Percentage of Entero-<br>bacteriales isolates<br>producing extended-<br>spectrum beta-lacta-<br>mate in the ICU</td><td></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>Less than 10%</td><td>60 (29.9)</td><td>574 (26)</td><td>259 (24)</td><td>315 (27.9)</td><td></td><td>390 (28.5)</td><td>184 (21.9)</td><td></td></tr><tr><td>10 to 24.9%</td><td>45 (22.4)</td><td>469 (21.2)</td><td>223 (20.6)</td><td>246 (21.8)</td><td></td><td>318 (23.2)</td><td>151 (18)</td><td></td></tr><tr><td>25 to 100%</td><td>60 (29.9)</td><td>841 (38.1)</td><td>452 (41.8)</td><td>389 (34.5)</td><td></td><td>460 (33.6)</td><td>381 (45.4)</td><td></td></tr><tr><td>Unknown</td><td>36 (17.9)</td><td>325 (14.7)</td><td>147 (13.6)</td><td>178 (15.8)</td><td></td><td>202 (14.7)</td><td>123 (14.7)</td><td></td></tr><tr><td>Percentage of Entero-<br>bacteriales isolates<br>producing carbapen-<br>emases in the ICU</td><td></td><td></td><td></td><td></td><td>0.09</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>Less than 10%</td><td>111 (55.2)</td><td>1093 (49.5)</td><td>523 (48.4)</td><td>570 (50.5)</td><td></td><td>732 (53.4)</td><td>361 (43)</td><td></td></tr><tr><td>10 to 24.9%</td><td>25 (12.4)</td><td>285 (12.9)</td><td>157 (14.5)</td><td>128 (11.3)</td><td></td><td>160 (11.7)</td><td>125 (14.9)</td><td></td></tr><tr><td>25 to 100%</td><td>31 (15.4)</td><td>519 (23.5)</td><td>259 (24)</td><td>260 (23)</td><td></td><td>282 (20.6)</td><td>237 (28.2)</td><td></td></tr><tr><td>Unknown</td><td>34 (16.9)</td><td>312 (14.1)</td><td>142 (13.1)</td><td>170 (15.1)</td><td></td><td>196 (14.3)</td><td>116 (13.8)</td><td></td></tr></tbody></table>

ICU intensive care unit, AMR antimicrobial resistance, Miss missing data; Of note, missing data are counted at centre level in this table
represent a proxy measure for access to a highly func-
tional laboratory system in a mature healthcare setting
with multiple other protective factors. Further analy-
sis showed that 64% (n=128) of centres administered
aminoglycoside during the study period and, amongst
them, 35% (n=45) did not perform TDM for aminogly-
coside. Interestingly, models conducted in this subpop-
ulation showed similar results (eTables 9–10).

We observed that frequent consultation with clinical
pharmacists was significantly associated with decreased
28-day mortality. Up to now, a positive impact of
pharmacy consultation for ICU patients with severe
infections has been reported only from retrospective
database linkage [22], or by small localised studies [23,
24]. By ensuring optimal drug choice, avoiding interac-
tions and improving delivery with pharmacodynamic/
pharmacokinetic optimisation, clinical pharmacists
could have a significant role in providing safe and effec-
tive care to ICU patients with severe infections.

In settings with a low prevalence of multidrug-resistant microorganisms, screening for multidrug-resistant organism carriage could prevent the spread of such microorganisms by allowing a prompt implementation of infection prevention and control measures, thus decreasing the risk of cross-transmission [25]. We also found that screening for multidrug-resistant organism carriage was associated with an increased probability of adequate therapy within the first 24 h. This association was significant when multidrug microorganisms were tested on admission and at least once weekly. Awareness of multidrug-resistant microorganism colonisation in critically ill patients could, therefore, be crucial for the implementation of the best therapeutic management strategies. In this context, a recent systematic review and meta-regression analysis showed that patients colonised with carbapenem-resistant microorganisms were at increased risk of subsequent infection [26]. Interestingly, one third of patients included in the EUROBACT-2 study were not screened for multidrug-resistant organism carriage, highlighting room for improvement in several centres. Further discussion on ICU AMR factors associated with mortality is described in the supplementary material.

Our study showed an association between the presence
of intermediate care beds in the ICU and 28-day mortal-
ity in the EUROBACT-2 cohort. The role of intermedi-
ate care beds combined with ICU beds has been debated
in the literature in the last 2 decades [27]. On one hand,
intermediate care beds could provide more intensive
monitoring and patient management than the general
ward, thus impacting prognosis [27]. In this context, a
large cohort study highlighted the benefits of intermedi-
ate care beds in term of prognosis for severely ill patients

[28] and our international study underlined the impor-
tance of the presence of these beds, especially during
COVID-19 pandemic. On the other hand, the presence
of intermediate care beds may simply represent a less-
severe patient population. However, after adjusting for
severity on admission, we observed a significant associa-
tion with mortality, thus refuting this hypothesis.

Country factors were also associated with our process
and outcome indicators. We showed that decreasing
values of HDI were associated with a low probability of
adequate antimicrobial therapy and increased probability
of mortality, respectively. To our knowledge, country fac-
tors have not been investigated as dependent variables on
process and outcome indicators in critically ill patients
with HABSI due to difficult to obtain worldwide data.
HDI includes long and healthy life expectancy, educa-
tion, and a decent standard of living measured by gross
national income per capita [29]: our findings clearly high-
lighted the need for policy-mediated large-scale improve-
ments even for critically ill patients.

Our study has several limitations. Centres were pre-
dominantly from high-income and upper-middle-income
countries, which limits the generalisability of our results.
Second, data collection continued during the first year of
the COVID-19 pandemic, whereas the management of
HABSI in the different centres may have been modified
during this period. For this reason, we performed a sen-
sitivity analysis excluding centres that recruited COVID-
19 patients. Third, data collection was performed by
individual investigators in several ICUs, without on-site
monitoring. We mitigated the risk of inconsistencies with
online checks through the electronic case report file, and
by a close monitoring of the data quality and coherence
within each case report by at least one expert. Fourth, for
our multivariable models, we used backward selection
which could be sensitive to the sample size, the order of
variables, the correlation amongst variables, and the sig-
nificance level. Fifth, aggregated AMR ICU data on *Aci-
netobacter* spp. and *Pseudomonas* spp. were not available
in the EUROBACT-2 database. Sixth, adequacy within
24 h may be a debatable process outcome and could only
represent a proxy for the true adequacy of antimicrobial
treatment. Of note, a recent meta-analysis showed that
24 versus 48 h cut-off showed similar impact on mortal-
ity [30]. Seventh, the number of HABSI included in each
centre was low, thus decreasing reliability of adjusted
analyses.

Conclusion

Using a large high-quality international database, we
showed that TDM strategies, availability of clinical
pharmacists, weekly screening for multidrug-resistant
microorganisms carriage, VRE prevalence in HABSI and
<table><caption>Table 4 Country factors</caption><thead><tr><th></th><th>All centres (n = 201)</th><th>All patients (n = 2209)</th><th>No adequate treatment (n = 1081)</th><th>24 h adequate treatment (n = 1128)</th><th>p value</th><th>Alive or discharge alive at day-28 (n = 1370)</th><th>28-day mortality (n = 839)</th><th>p value</th></tr></thead><tbody><tr><td>OECD member</td><td>137 (68.2)</td><td>1681 (76.1)</td><td>810 (74.9)</td><td>871 (77.2)</td><td>0.21</td><td>1040 (75.9)</td><td>641 (76.4)</td><td>0.79</td></tr><tr><td>Human Development Index</td><td>0.88 [0.82; 0.90]</td><td>0.86 [0.82; 0.90]</td><td>0.83 [0.82; 0.90]</td><td>0.89 [0.82; 0.90]</td><td>&lt; 0.01</td><td>0.89 [0.82; 0.90]</td><td>0.83 [0.82; 0.90]</td><td>&lt; 0.01</td></tr><tr><td>National action plan on AMR (miss = 4)</td><td></td><td></td><td></td><td></td><td>0.03</td><td></td><td></td><td>&lt; 0.01</td></tr><tr><td>Not implemented</td><td>79 (40.1)</td><td>1008 (46.5)</td><td>523 (48.8)</td><td>485 (44.2)</td><td></td><td>580 (43.3)</td><td>428 (51.8)</td><td></td></tr><tr><td>Developed and implemented</td><td>118 (59.9)</td><td>1160 (53.5)</td><td>548 (51.2)</td><td>612 (55.8)</td><td></td><td>761 (56.7)</td><td>399 (48.2)</td><td></td></tr><tr><td>Training and professional education on AMR (miss = 8)</td><td></td><td></td><td></td><td></td><td>&lt; 0.01</td><td></td><td></td><td>&lt; 0.01</td></tr><tr><td>Never/in some pre-service training and continuing professional development</td><td>74 (38.3)</td><td>1048 (49.2)</td><td>571 (54.2)</td><td>477 (44.2)</td><td></td><td>576 (43.7)</td><td>472 (58)</td><td></td></tr><tr><td>In all relevant pre-service training and continuing professional development</td><td>119 (61.7)</td><td>1084 (50.8)</td><td>483 (45.8)</td><td>601 (55.8)</td><td></td><td>742 (56.3)</td><td>342 (42)</td><td></td></tr><tr><td>National monitoring system for consumption and rational use of antimicrobials (miss = 4)</td><td></td><td></td><td></td><td></td><td>0.05</td><td></td><td></td><td>0.12</td></tr><tr><td>None</td><td>7 (3.6)</td><td>64 (3)</td><td>26 (2.4)</td><td>38 (3.5)</td><td></td><td>41 (3.1)</td><td>23 (2.8)</td><td></td></tr><tr><td>National sales and consumption</td><td>17 (8.6)</td><td>111 (5.1)</td><td>54 (5)</td><td>57 (5.2)</td><td></td><td>62 (4.6)</td><td>49 (5.9)</td><td></td></tr><tr><td>National and/or sub-national sales and consumption</td><td>46 (23.4)</td><td>554 (25.6)</td><td>263 (24.6)</td><td>291 (26.5)</td><td></td><td>359 (26.8)</td><td>195 (23.6)</td><td></td></tr><tr><td>Prescribing practises and antibiotic use</td><td>15 (7.6)</td><td>114 (5.3)</td><td>70 (6.5)</td><td>44 (4)</td><td></td><td>61 (4.5)</td><td>53 (6.4)</td><td></td></tr><tr><td>Prescribing practises, antibiotic use, national sales, and consumption</td><td>112 (56.9)</td><td>1325 (61.1)</td><td>658 (61.4)</td><td>667 (60.8)</td><td></td><td>818 (61)</td><td>507 (61.3)</td><td></td></tr><tr><td>National surveillance system for AMR<sup>a</sup> (miss = 9)</td><td></td><td></td><td></td><td></td><td>&lt; 0.01</td><td></td><td></td><td>&lt; 0.01</td></tr><tr><td>No reports</td><td>51 (26.6)</td><td>886 (41.5)</td><td>492 (46.9)</td><td>394 (36.4)</td><td></td><td>486 (36.9)</td><td>400 (49)</td><td></td></tr><tr><td>Collects data and produces reports</td><td>141 (73.4)</td><td>1247 (58.5)</td><td>558 (53.1)</td><td>689 (63.6)</td><td></td><td>830 (63.1)</td><td>417 (51)</td><td></td></tr></tbody></table>
<table><caption>Table 4 (Continued)</caption><thead><tr><th></th><th>All centres<br>(n = 201)</th><th>All patients<br>(n = 2209)</th><th>No adequate treat-<br>ment (n = 1081)</th><th>24 h adequate treat-<br>ment (n = 1128)</th><th>p value</th><th>Alive or discharge<br>alive at day-28<br>(n = 1370)</th><th>28-day mortality<br>(n = 839)</th><th>p value</th></tr></thead><tbody><tr><td>Policies for optimising<br>antimicrobial use<br>(miss = 4)</td><td></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>None or in some<br>healthcare facilities,<br>n (%)</td><td>91 (46.2)</td><td>1197 (55.2)</td><td>628 (58.6)</td><td>569 (51.9)</td><td></td><td>682 (50.9)</td><td>515 (62.3)</td><td></td></tr><tr><td>In most healthcare/<br>guidelines imple-<br>mented for all, n (%)</td><td>106 (53.8)</td><td>971 (44.8)</td><td>443 (41.4)</td><td>528 (48.1)</td><td></td><td>659 (49.1)</td><td>312 (37.7)</td><td></td></tr><tr><td>Region</td><td></td><td></td><td></td><td></td><td>0.22</td><td></td><td></td><td>0.01</td></tr><tr><td>The Americas</td><td>6 (3)</td><td>46 (2.1)</td><td>22 (2)</td><td>24 (2.1)</td><td></td><td>30 (2.2)</td><td>16 (1.9)</td><td></td></tr><tr><td>East Asia and Pacific</td><td>34 (16.9)</td><td>304 (13.8)</td><td>132 (12.2)</td><td>172 (15.2)</td><td></td><td>210 (15.3)</td><td>94 (11.2)</td><td></td></tr><tr><td>Europe and Central<br>Asia</td><td>130 (64.7)</td><td>1608 (72.8)</td><td>799 (73.9)</td><td>809 (71.7)</td><td></td><td>966 (70.5)</td><td>642 (76.5)</td><td></td></tr><tr><td>Middle East and<br>Africa</td><td>24 (11.9)</td><td>214 (9.7)</td><td>106 (9.8)</td><td>108 (9.6)</td><td></td><td>144 (10.5)</td><td>70 (8.3)</td><td></td></tr><tr><td>South Asia</td><td>7 (3.5)</td><td>37 (1.7)</td><td>22 (2)</td><td>15 (1.3)</td><td></td><td>20 (1.5)</td><td>17 (2)</td><td></td></tr></tbody></table>

OECD Organisation for Economic Co-operation and Development, AMR antimicrobial resistance, Miss missing data; of note, missing data are counted at centre level in this table
Human Development Index could substantially be asso-
ciated with process and outcome indicators. Centre- and
country-specific factors should be included in further
prospective international studies investigating severe
infections in critically ill patients.

**Supplementary Information**

The online version contains supplementary material available at https://doi.
org/10.1007/s00134-024-07348-0.

Author details

¹ Infection Control Program, Geneva University Hospitals and Faculty of Medicine, World Health Organization Collaborating Centre, Geneva, Switzerland.

² IAME UMR 1137, INSERM, Université Paris-Cité, Paris, France. ³ Intensive Care Unit, Redcliffe Hospital, Brisbane, Australia. ⁴ Queensland Critical Care Research Network (QCCRN), Brisbane, QLD, Australia. ⁵ Queensland University of Technology, Brisbane, QLD, Australia. ⁶ Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. ⁷ Médecine Intensive Réanimation, Centre Hospitalier Régional d'Orléans, 14, Avenue de L'Hôpital, 45000 Orléans, France. ⁸ Institut Maurice Rapin, Hôpital Henri Mondor, Créteil, France.

⁹ Department of Infectious Diseases, Hacettepe University School of Medicine, Ankara, Turkey. ¹⁰ Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey. ¹¹ Faculty of Medicine, Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia. ¹² Department of Anesthesiology and Intensive Care Unit, Hospital Nord, Aix Marseille University, Assistance Publique Hôpitaux Universitaires de Marseille, Marseille, France. ¹³ Infectious Diseases Clinic, Department of Health Sciences, University of Genoa and Ospedale Policlinico San Martino, Genoa, Italy. ¹⁴ Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. ¹⁵ Division of Immunology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. ¹⁶ JVF Intensive Care Unit, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. ¹⁷ Intensive Care Unit, Papageorgiou University Affiliated Hospital, Thessaloniki, Greece. ¹⁸ Intensive Care Medicine Department, Centro Hospitalar Universitário Sao Joao, Porto, Portugal.

¹⁹ Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal. ²⁰ Infection and Sepsis ID Group, Porto, Portugal. ²¹ Intensive Care Department, SODIR-VHIR Research Group, Vall d'Hebron University Hospital, Barcelona, Spain. ²² Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Nanjing Zhongda Hospital, Southeast University, Nanjing 210009, China. ²³ Department of Anesthesia, Intensive Care and Emergency, Città della Salute e della Scienza University Hospital, Turin, Italy. ²⁴ Department of Surgical Sciences, University of Turin, Turin, Italy.

²⁵ Department of Precision Medicine in Medical, Surgical and Critical Care (Me. Pre.C.C.), University of Palermo, Palermo, Italy. ²⁶ Department of Anesthesia, Intensive Care and Emergency, University Hospital Policlinico Paolo Giaccone, University of Palermo, Via del Vespro129, 90127 Palermo, Italy. ²⁷ Department of Infectious Diseases and Clinical Microbiology, Ankara City Hospital, Ankara Yildirim Beyazit University, Ankara, Turkey. ²⁸ Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium. ²⁹ Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. ³⁰ Medical and Infectious Diseases Intensive Care Unit, AP-HP, Bichat-Claude Bernard University Hospital, 46 Rue Henri Huchard, 75877 Paris Cedex, France. ³¹ Biostatistic Department, Outcomerea, 93700 Drancy, France.

Acknowledgements

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

Fourie, Kevin Lapland, Mahesh Ramanan, James Walsham, Jason Meyer, Edward Litton, Anna Maria Palermo, Timothy Yap, Ege Eroglu, Antony George Attokaran, C'havala Jaramillo, Khalid Mahmood Khan Nafees, Nurhikmahtul Agilah Haji Abd Rashid, Haji Adi Muhamad Ibnu Walid, Tomas Mon, P. Dhakshina Moorthi, Shah Sudhirchandra, Dhadappa Damodar Sridharan, Qiu Haibo, Xie Jianfeng, Lu Wei-Hua, Wang Zhen, Chuanyun Qian, Jili Luo, Xiaomei Chen, Hao Wang, Peng Zhao, Juan Zhao, Qiu Wusi, Chen Mingmin, Lei Xu, Chengfen Yin, Ruilan Wang, Jinfeng Wang, Yongjie Yin, Min Zhang, Jilu Ye, Chungfang Hu, Suming Zhou, Min Huang, Jing Yan, Yan Wang, Bingyu Qin, Ling Ye, Xie Weifeng, Li Peije, Nan Geng, Yoshiro Hayashi, Toshiyuki Karumai, Masaki Yamasaki, Satoru Hashimoto, Koji Hosokawa, Jun Makino, Takeo Matsuyoshi, Akira Kuriyama, Hidenobu Shigemitsu, Yuka Mishima, Michio Nagashima, Hideki Yoshida, Shigeki Fujitani, Koichiro Omori, Hiroshi Rinka, Hiroki Saito, Kaori Atobe, Hideaki Kato, Shunsuke Takaki, M. Shahnaz Hasan, Muhamad Fadhil Hadi Jamaluddin, Lee See Pheng, Sheshendrasurian Visvalingam, Mun Thing Liew, Siong Ling Danny Wong, Kean Khang Fong, Hamizah Bt Abdul Rahman, Zuraini Md Noor, Lee Kok Tong, Abd. Hamid Azman, Mohd Zulfakar Mazlan, Saedah Ali, Kyeongman Jeon, Sang-Min Lee, Sunghoon Park, Seung Yong Park, Sung Yoon Lim, Qing Yuan Goh, Shin Yi Ng, Sui An Lie, Andrea Lay Hoon Kwa, Ken Junyeh Goh, Reza Yunkai Li, Caroline Yu Ming Ong, Jia Yan Lim, Jessica Lishan Quah, Kangqi Ng, Louis Xiang Long Ng, Yu Chang Yeh, Nai-Kuan Chou, Cong-Tat Cia, Ting-Yu Hu, Li-Kuo Kuo, Shih-Chi Ku, Phunsup Wongsurakiat, Yutthana Apichatbutr, Supatra Chiewroongroj, Rashid Nadeem, Ashraf El Houfi, Adel Alsisi, Amr Elhadidy, Mina Barsoum, Nermin Osman, Tarek Mostafa, Mohamed Elbahna- sayeh, Ahmed Saber, Amer Aldhalia, Omar Almendouah, Ahmed Elsayed, Merihan A. Elbadawy, Ahmed K. Awad, Hanan M. Hemead, Farid Zand, Maryam Ouhadian, Seyed Hamid Borsi, Zahra Mehraban, Davod Kashipazha, Fatemeh Ahmadi, Mohsen Savae, Farhad Soltani, Mahboobeh Rashidi, Reza Baghban- ian, Fatemeh Javaherforoosh, Fereshteh Amiri, Arash Kiani, Mohammad Amin Zargar, Ata Mahmoodpoor, Fatemeh Aalinezhad, Gholamreza Dabiri, Golnar Sabetian, Hakimeh Sarshad, Mansoor Masjedi, Ramin Tajvidi, Seyed Moham- mad Nasirodin Tabatabaei, Abdullah Khudhur Ahmed, Pierre Singer, Ilya Kagan, Merav Rigler, Daniel Belman, Phillip Levin, Belal Harara, Adei Diab, Fayez Abilama, Rebecca Abrahim, Aya Fares, Ahmad Buimsaedah, Marwa Gamra, Ahmed Aqeela, Almajdoub Ali Mohammed Ali, Ahmed Gaber Sadik Homaidan, Bushray Almiqlash, Hala Bilkhayr, Ahmad Bouhuwaish, Ahmed Sa Tahan, Eman Abdulwahed, Fathi A. Abousnina, Aisha Khaled Hdada, Rania Jobran, Hayat Ben Hasan, Rabab Shaban Ben Hasan, Issam Serghini, Rachid Seddiki, Brahim Boukatta, Nabil Kanjaa, Doumiri Mouhssine, Maazouzi Ahmed Wajdi, Tarek Dendane, Amine Ali Zeggwagh, Brahim Housni, Oujidi Younes, Abdelhamid Hachimi, A. Ghannam, Z. Belkhadir, Sarah Amro, Mustafa Abu Jayyab, Ali Ait Hssain, Abdurahaman Elbuzidi, Edin Karic, Marcus Lance, Shaikh Nissar, Hend Sallam, Omar Elrabi, Ghaleb A. Almekhlafia, Maher Awad, Ahmed Aljabbary, Mohammad Karam Chaaban, Natalia Abu-Sayf, Mohammad Al-Jadaan, Lubna Bahr, Mounir Bouaziz, Olfa Turki, Walid Sellami, Pablo Centeno, Lic Natalia Morvillo, José Oscar Acevedo, Patricia Mabel Lopez, Rubén Fernández, Matías Segura, Dra Marta Aparicio, Microbiologa Irene Alonzo, Yanina Nuccetelli, Pablo Montefiore, Luis Felipe Reyes, Luis Felipe Reyes, Silvio A. Namendys-Silva, Juan P. Romero-Gonzalez, Mariana Hermosillo, Roberto Alejandro Castillo, Jesús Nicolás Pantoja Leal, Candy Garcia Aguilar, Mara Ocotlan Gonzalez Herrera, Missael Vladimir Espinoza Villafuerte, Manuel Lomeli-Teran, Jose G. Dominguez-Cherit, Adrian Davalos-Alvarez, Silvio A. Namendys-Silva, Luis Sánchez-Hurtado, Brigitte Tejeda-Huezo, Orlando R. Perez-Nieto, Ernesto Deloya Tomas, Liesbet De Bus, Jan De Waele, Isabelle Hollevoet, Wouter Denys, Marc Bourgeois, Sofie F. M. Vanderhaeghen, Jean-Baptiste Mesland, Pierre Henin, Lionel Haentjens, Patrick Biston, Cindérella Noel, Nathalie Layos, Benoît Misset, Nicolas De Schryver, Nicolas Serck, Xavier Wittebole, Elisabeth De Waele, Godelive Opdenacker, Pedja Kovacevic, Biljana Zlojutro, Aida Custovic, Ina Filipovic-Grcic, Radovan Radonic, Ana Vujaklija Brajkovic, Jasminka Persec, Sanja Sakan, Mario Nikolic, Hrvoje Lasic, Marc Leone, Charlotte Arbelot, Jean-François Timsit, Juliette Patrier, N. Zappela, P. Montravers, Thierry Dulac, Jérémy Castanera, Johann Auchabie, Anthony Le Meur, A. Marchalot, M. Beuzelin, Alexandre Massri, Charlotte Guesdon, Etienne Escudier, Philippe Mateu, Jérémy Rosman, Olivier Leroy, Serge Alfandari, Alexandru Nica, Bertrand Souweine, Elisabeth Coupez, Thibault Duburcq, Eric Kipnis, Perrine Bortolotti, Mathieu Le Souhaitier, Jean-Paul Mira, Pierre Garcon, Matthieu Duprey, Matthiel Thyrault, Rémi Paulet, François Philippart, Marc Tran, Cédric Bruel, Emmanuel Weiss, Sylvie Janny, Arnaud Focrier, Pierre-François Perrigault, Flora Djanikian, François Barbier, Marc Gainnier, Jérémy Bourenne, Guillaume Louis, Roland Smonig, Laurent
Argaud, Thomas Baudry, Armand Mekonted Dessap, Keyvan Razazi, Pierre Kalfon, Gaëtan Badre, Romaric Larcher, Jean-Yves Lefrant, Claire Roger, Benjamine Sarton, Stein Silva, Sophie Demeret, Loïc Le Guennec, Shidasp Siami, Christelle Aparicio, Guillaume Voiriot, Muriel Fartoukh, Claire Dahyot-Fizelier, Nadia Imzi, Kada Klouche, Hendrik Bracht, Sandra Hoheisen, Frank Bloos, Daniel Thomas-Rueddel, Sirak Petros, Bastian Pasieka, Simon Dubler, Karsten Schmidt, Antje Gottschalk, Carola Wempe, Philippe Lepper, Carlos Metz, Dmitriy Viderman, Yerlan Umbetzhanov, Miras Mugazov, Yelena Bazhykayeva, Zhannur Kaligozhin, Baurzhan Babashev, Yevgeniy Merenkov, Talgat Temirov, Kostoula Arvaniti, Dimitrios Smyrniotis, Vasiliki Psallida, Georgios Fildisis, Vasiliki Souountsi, Evangelos Kaimakamis, Cristina Iasonidou, Sofia Papoti, Foteini Renta, Maria Vasileiou, Vasiliki Romanou, Vasiliki Koutsoukou, Mariana Kristina Matei, Leora Moldovan, Ilias Karaiskos, Harry Paskalis, Kyriaki Marmanidou, M. Papanikolaou, C. Kampolis, Marina Oikonomou, Evangelos Kogkopoulos, Charikleia Nikolaou, Anastasios Sakkalis, Marinos Chatzis, Maria Georgopoulos, Anna Efthymiou, Vasiliki Chantziara, Aikaterini Sakagianni, Zoi Athanasa, Eirini Papageorgiou, Fadi Ali, Georges Dimopoulos, Mariota Panagiota Almiroudi, Polychronis Malliotakis, Diamantina Marouli, Vasiliki Theodorou, Ioannis Retselas, Vasilios Kouroulas, Georgios Papathanakos, Giorgia Montrucchio, Gabriele Sales, Gennaro De Pascale, Luca Maria Montini, Simone Carelli, Joel Vargas, Valentina Di Gravio, Daniele Roberto Giacobbe, Angelo Gratarola, Elisa Porcile, Michele Mirabella, Ivan Daroui, Giovanni Lodi, Francesco Zuccaro, Maria Grazia Schlevenin, Paolo Pelosi, Denise Battaglini, Andrea Cortegiani, Mariachiara Ippolito, Davide Bellina, Andrea Di Guardo, Lorella Pelagalli, Marco Covotta, Monica Rocco, Silvia Fiorelli, Antonella Cotoia, Anna Chiara Rizzo, Adam Mikstacki, Barbara Tamowicz, Irmina Kaptur Komorowska, Anna Szczesniak, Jozef Bojko, Anna Kotkowska, Paulina Walczak-Wieteska, Dominika Wasowska, Tomasz Nowakowski, Hanna Broda, Mariusz Peichota, Iwona Pietraszek-Grzywaczewska, Ignacio Martin-Loeches, Alessandra Bisanti, Nuno Cartoze, Tiago Pereira, Nádia Guimarães, Madalena Alves, Ana Josefina Pinheiro Marques, Ana Rios Pinto, Andriy Krystopchuk, Ana Teresa, António Manuel Pereira de Figueiredo, Isabel Botelho, Tiago Duarte, Vasco Costa, Rui Pedro Cunha, Elena Molinos, Tito da Costa, Sara Ledo, Joana Queiró, Dulce Pascoalinho, Cristina Nunes, José Pedro Moura, Énio Pereira, António Carvalho Mendes, Liana Valeanu, Serban Bubenek-Turconi, Ioana Marina Grintescu, Cristian Cobilinschi, Daniela Carmen Filipescu, Cornelia Elena Predoi, Dana Tomescu, Mihai Popescu, Alexandra Marcu, Ioana Grigoras, Olguta Lungu, Alexey Gritsan, Anastasia Anderzhanova, Yulia Meleshkina, Marat Magomedov, Nadezhda Zubareva, Maksim Tribulev, Denis Gaigolnik, Aleksandr Eremenko, Natala Vistovskaya, Maria Chukina, Vladislav Belskiy, Mikhail Furman, Ricard Ferrer Rocca, Maria Martinez, Vanessa Casares, Paula Vera, Matias Flores, Joaquin Amador Amerigo, Maria Pilar Gracia Arnillas, Rosana Munoz Bermudez, Fernando Armestar, Beatriz Catalan, Regina Roig, Laura Raguier, María Dolores Quesada, Emilio Diaz Santos, Gemma Gomà, Alejandro Ubeda, Dra Maria Salgado, Lorena Forcelledo Espina, Emilio Garcia Prieto, Dra Mj Asensio, Dra M. Rodriguez, Emilio Maseda, Alejandro Suarez De La Rica, J. Ignacio Ayestaran, Mariana Novo, Miguel Angel Blasco-Navalpotro, Alberto Orejas Gallego, Fredrik Sjövall, Dzana Spahic, Carl Johan Svensson, Michael Haney, Alicia Edin, Joyce Åkerlund, Lina De Geer, Josef Prazak, Stephan Jakob, Jl Pagani, S. Abed-Maillard, Murat Akova, Abdullah Tarik Aslan, Arif Timuroglu, Sesin Kocagoz, Hulya Kusoglu, Selcuk Mehtap, Solakoğlu Ceyhun, Neriman Defne Altintas, Leyla Talan, Bircan Kayaslan, Ayşe Kaya Kalem, Ibrahim Kurt, Murat Telli, Barcin Ozturk, Çiğdem Erol, Emine Kubra Dindar Demiray, Sait Çolak, Türkay Akbas, Kursat Gundogan, Ali Sari, Canan Agalar, Onur Çolak, Nurcan N. Baykam, Ozlem O. Akdogan, Mesut Yilmaz, Burcu Tunay, Rumeysa Cakmak, Nese Saltoglu, Ridvan Karaali, İftihar Akosal, Firdews Aksoy, Ahmet Eroglu, Kemal Tolga Saracoglu, Yeliz Bilir, Seda Guzeldag, Gulden Ersoz, Guliz Evik, Hulya Sungurtekin, Cansu Ozgen, Cem Erdoğan, Yunus Gürbüz, Nilgün Altin, Yasar Bayindir, Yasemin Ersoy, Senay Goksu, Ahmet Akyol, Ayse Batirel, Sabahat Cagan Aktas, Andrew Conway Morris, Matthew Routledge, Andrew Conway Morris, Ari Ercole, David Antcliffe, Roceld Rojo, Kate Tizard, Maria Faulkner, Amanda Cowton, Melanie Kent, Ashok Raj, Artemis Zormpa, George Tinaslanidis, Reena Khade, Tomasz Torlinski, Randeep Mulhi, Shraddha Goyal, Manan Bajaj, Marina Soltan, Aimee Yonan, Rachael Dolan, Aimee Johnson, Caroline Macfie, James Lennard, Maie Templeton, Sonia Sousa Arias, Uwe Franke, Keith Hugill, Hollie Angell, Benjamin J. Parcell, Katherine Cobb, Stephen Cole, Tim Smith, Clive Graham, Jaroslav Cerman, Allison Keegan, Jenny Ritzema, Amanda Sanderson, Ashraf Roshdy, Tamas Szakmany, Tom Baumer, Rebecca Longbottom, Daniel Hall, Kate Tatham, S. Loftus, A. Husain, E. Black, S. Jhanji, R. Rao Baikady, Peter Mcguigan, Rachel Mckee, Santhana Kannan, Supriya Antrolikar, Nicholas Marsden, Valentina Della Torre, Dorota

Banach, Ahmed Zaki, Matthew Jackson, Moses Chikungwa, Ben Attwood, Jamie Patel, Rebecca E. Tilley, Miss Sally K. Humphreys, Paul Jean Renaud, Anton Sokhan, Yaroslava Burma, Wendy Sligl, Nadia Baig, Lorena McCoshen, Demetrios J. Kutsogiannis, Wendy Sligl, Patricia Thompson, Tayne Hewer, Raihan Rabbani, Shihan Mahmud Redwanul Huq, Rajib Hasan, Mohammad Motiul Islam, Mohan Gurjar, Arvind Baronia, Nikhil Kothari, Ankur Sharma, Saurabh Karmakar, Priya Sharma, Janardan Nimbolkar, Pratit Samdani, R. Vaidyanathan, Noor Ahmedi Rubina, Nikhilesh Jain, Madhumati Pahuja, Ritu Singh, Saurav Shekhar, Syed Nabeel Muzaffar, Ahmad Ozair, Suhail Sarwar Siddiqui, Payel Bose, Avijatri Datta, Darshana Rathod, Mayur Patel, M. K. Renuka, Sailaja K. Baby, Carol Dsilva, Jagadish Chandran, Pralay Ghosh, Sudipta Mukherjee, Kaladhar Sheshala, Krushna Chandra Misra, Saidu Yusuf Yakubu, Euphemia Mgbosoro Ugwu, John O. Olatosi, Ibironke Desalu, Gabriel Asiyanbi, Motunrayo Oladimeji, Olusola Idowu, Fowotade Adeola, Melanie Mc Cree, Ali Adil Ali Karar, Elfayadh Saidahmed, Hytham K. S. Hamid.

## Author contributions

NB, SR, AT and JFT designed and conceptualised the study. All co-authors acquired the data in their countries. SR, NB, NS and JFT did the statistical analysis. SR performed data curation. JFT and AT acquired funding. NB, SR, AT and JFT analysed and interpreted the data. NB, AT, NS and JFT drafted the manuscript. All authors critically reviewed the manuscript and approved the final report.

## Funding

Open access funding provided by University of Geneva. Research grants were obtained from the European Society of Intensive Care Medicine (ESICM), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP), the Norva Dahlia foundation and the Redcliffe Hospital Private Practice Trust Fund.

## Availability of data and material

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

## Declarations

## Conflicts of interest

NB received a Mobility grant from the Swiss National Science Foundation (Grant number: P400PM_183865). JJDW is a senior clinical investigator funded by the Research Foundation Flanders (FWO, Ref. 1881020N). ACM is supported by a Medical Research Council Clinician Scientist Fellowship (MR/V006118/1) and received speaking fees from Fischer & Paykel, Biomerieux; he participated in scientific advisory board of Cambridge infection diagnostics; he received support for the present manuscript by the medical research council (Clinician Scientist Fellowship grant number: MR/V006118/1). ML received consulting fees from LFB, Shionogi, AOP Pharma and Viatris outside of this project. RF has received consulting fees from Inotrem, Pfizer and Cytosorbent and honoraria for lectures from Shionogi, MSD, Menarini, Thermofisher and Gilead. GM received payment for honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Thermofisher, Gilead, Pfizer and 3 M; and she participated on a data Safety Monitoring Board or Advisory Board by Gilead and 3 M. AC received fees for lectures and scientific consultancies by Gilead, MSD, Mundipharma, Pfizer. LDB participated on data safety monitoring or advisory board of MSD. MB received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Angelini, Biomerieux, Cidara, Gilead, Menarini, MSD, Pfizer, and Shionogi. MB participated on data safety monitoring board or advisory board of Angelini, Biomerieux, Cidara, Gilead, Menarini, MSD, Pfizer, and Shionogi. MA participated on a data safety board for GSK and is the president of the International Immunocompromised Host Society.

## Ethics approval

The initial ethical approval as a low-risk research project with waiver of individual consent was granted by the Ethics Committee of the Royal Brisbane & Women's Hospital, Queensland, Australia (number: LNR/2019/QRBW/48376). Each study centre obtained ethical, governance and any other relevant approvals according to regional and/or national regulations.
**Consent for publication**

Not applicable.

**Open Access**

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Received: 4 October 2023 Accepted: 5 February 2024

Published: 18 March 2024

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