Epidemiology and Determinants of Outcomes of Hospital Acquired Blood Stream Infections in the Intensive Care: the Eurobact II Multinational Cohort Study
Conditions: Bacteremia, Sepsis, Hospital Acquired Condition, Resistance Bacterial
Sponsor: Outcome Rea

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EUROBACT II 
 
 
 
 
 
 
 
 
Epidemiology and determinants of outcomes of Hospital 
Acquired Blood Stream Infections in the Intensive Care. 
 
A multinational cohort study by the ESICM Trials Group. 
 
  
 
 
 
 
STUDY PROTOCOL 
V 1.06 
19/04/2019 
 
Eurobact II is endorsed by:  
The ESICM Infection Section 
ESCMID Study Group for Infections in Critically Ill Patients – ESGCIP 
Asia Pacific Association of Critical Care Medicine - APACCM 
 
 

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Title  
Epidemiology and determinant of outcomes of hospital acquired Blood Stream 
Infections in the intensive care. (Eurobact II) 
Design 
Prospective observational multinational, multicenter cohort study. 
Target pop.  
Patients with a Hospital acquired blood stream infection treated in the ICU. 
Interventions 
None  
Study 
objectives/ 
research 
questions 
Primary outcome measure 
Day 28 mortality in patients with HA-BSI  
Secondary outcome measures 
Progress of organ failures at day 7 
Days free of RRT/MV/Vasopressors/ICU 
Objectives 
• To describe the organisation of microbiology processing 
o Communication, changes with day/night/weekend. 
o Use of rapid testing for resistance patterns (VRE, CPE, others) 
o Use of Maldi-Tof for rapid identification. 
• To describe the determinants of outcomes of HA-BSI, specifically the effects 
o Source 
o Microorganisms. 
 Species and antibiogram 
 Resistance and “difficult to treat” status 
 Mechanism of resistance and specific enzymes (ESBL, 
Carbapenemase producers, VRE…) 
 MICs for Difficult to treat pathogens. 
o Antimicrobial therapy 
 Timing, Spectrum and adequacy 
 Combination therapy 
 Dose and Mode of administration 
 Modifications including escalation and de-escalation. 
o Source control, including timing and adequacy. 
o Patient specific factors 
o Severity of shock, organ failures and lactate levels 
o Organisational factors 
• To assess the respective impact of the source the microorganism and the 
components of therapy on outcomes. 
• To describe the determinants of management of HA-BSI, including 
o Diagnostic methods and how they influence starting and modifying 
therapy (MALDI-TOF and molecular vs traditional methods for 
identification, speciation and susceptibility reporting) 
o Type, dosing and duration of antimicrobial therapy 
o Source control 
o Other treatments for sepsis (steroids) 
• To describe epidemiological changes since the Eurobact study. 
Study 
duration 
3 months or 10 included patients per center. 
Follow-up 
period 
28 days or hospital discharge. 

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Table of Contents 
Rationale: ........................................................................................................................ 4 
Objectives and outcome measures: ................................................................................... 5 
Design: ............................................................................................................................. 5 
Intervention: .................................................................................................................... 6 
Patient Inclusion criteria: .................................................................................................. 6 
Exclusion criteria: ............................................................................................................. 6 
Duration of the study: ....................................................................................................... 6 
Unit participation criteria: ................................................................................................ 6 
Ethical considerations. ...................................................................................................... 7 
Timeline ........................................................................................................................... 7 
Data to record: ................................................................................................................. 8 
Operational considerations ............................................................................................... 9 
Principal investigators .............................................................................................................. 9 
Organisational committee: ....................................................................................................... 9 
Operational committee: ........................................................................................................... 9 
National Coordinator: ............................................................................................................ 10 
Local Primary Investigators (LPI) ............................................................................................. 10 
Electronic data capture: ......................................................................................................... 10 
Financial considerations ................................................................................................. 11 
Sponsor and Legal considerations ................................................................................... 11 
Security, confidentiality and data quality processes ........................................................ 11 
Use of data and property ................................................................................................ 11 
Statistical analysis .......................................................................................................... 11 
Rules for publication and authorship .............................................................................. 12 
Pre-Planned subgroup and ancillary analysis. ................................................................. 12 
Organization .................................................................................................................. 13 
References...................................................................................................................... 14 
Version record ................................................................................................................ 15 
 
 
 

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Rationale: 
 
Sepsis is recognised as one of the leading causes of mortality and has become a global 
healthcare priority. It is defined as life-threatening organ dysfunction caused by a 
dysregulated host response to infection [1]. In a large multinational study Infections were 
thought to be present in 51% of ICU patients, of which 30% were culture negative [2].  
Blood stream infection (BSI) is defined as the presence of a pathogen in the blood stream of 
a patient.  As such, and once contaminants are excluded, BSI is the only cause of sepsis where 
the presence of an infection and the pathogen are known with certainty. This makes BSI the 
perfect model of infection to study the effects of the micro-organism on the patient, and the 
effects of the antibiotics and other treatments on survival. 
The Eurobact 1 study collected multinational data on HA-BSI in 2010-11 as part of a large 
multicentric collaboration coordinated by the infection section of the ESICM [3]. By including 
1156 patients with HA-BSI from 162 ICUs in 24 countries this was the largest and most cited 
study of HA-BSI treated in the ICU. It has been topical in describing the relationship between 
antimicrobial resistance (AMR) and increased delays in effective drug therapy and how 
resistance is independently associated with mortality.  
While growing AMR and sepsis makes the headlines of mainstream media, the problematic 
of growing AMR was recently highlighted in a joint roundtable hosted by the European Society 
of Intensive Care Medicine (ESICM) and the European Society of Clinical Microbiology and 
Infectious Diseases (ESCMID) and the World Alliance Against Antimicrobial Resistance 
(WAAAR) [4]. The panel published a list of 6 recommendations, of which 1 was to make AMR 
a priority in research activities, 2 to document Gram Negative AMR infection from a global 
perspective and 4 to collect data on treatment and outcome of XDR/PDR infections. 
Furthermore recent changes in the overall management of patients with sepsis and shock and 
a reported change in prognosis makes it urgent to obtain current data on HA-BSI in the 
critically ill [5, 6]. 
Eurobact 2 was developed by the infection section of the ESICM to specifically answer those 
questions and recommendations. By targeting HA-BSI in a large multinational study we will 
obtain granular data and investigate how management and outcomes of patients with severe 
hospital acquired infections may have changed while there has been a worldwide increase in 
AMR.  
 
 
 

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Objectives and outcome measures: 
Primary outcome measure 
Day 28 mortality in patients with HA-BSI  
Secondary outcome measures 
Progress of organ failures at day 7 
Days free of RRT/MV/Vasopressors/ICU 
 
Objectives 
• To describe the epidemiology and determinants of outcome of HA-BSI treated in the ICU 
• To describe the organisation of microbiology processing 
o Communication, changes with day/night/weekend. 
o Use of rapid testing for resistance patters (VRE, CPE, others) 
o Use of Maldi-Tof for rapid identification. 
• To describe the determinants of outcomes of HA-BSI and specifically the effects of: 
o Source 
o Microorganisms. 
 Species and antibiogram 
 Resistance and difficult to treat status 
 Mechanism of resistance and specific enzymes (ESBL, Carbapenemase 
producers, VRE…) 
 MICs for Difficult to treat pathogens. 
o Antimicrobial therapy 
 Timing 
 Spectrum and adequacy 
 Combination therapy 
 Dose 
 Mode of administration 
 Modifications including escalation and de-escalation. 
o Source control, including timing and adequacy. 
o Patient specific factors 
o Severity of shock, organ failures and lactate levels 
o Organisational factors 
• To describe the determinants of management of HA-BSI, including 
o Diagnostic methods and how they influences starting and modifying therapy 
(MALDI-TOF and molecular vs traditional methods for identification, speciation 
and susceptibility reporting.) 
o Type, dosing and duration of antimicrobial therapy 
o Source control 
o Other treatments for sepsis (steroids) 
• To describe epidemiological changes since the Eurobact study. 
 
Design: 
Prospective observational multicenter cohort study. 
 

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Intervention:  
none 
 
Patient Inclusion criteria: 
All adult (Age > 18 Years) patients with a Hospital Acquired Bloodstream Infection (HA-BSI) 
treated in the ICU.  
HA-BSI is defined as a positive blood culture (BC) sampled after 48 hours following hospital 
admission. 
 
For CNS and common contaminants (coagulase-negative staphylococci, Corynebacterium 
species, Bacillus species, Propionibacterium species, Aerococcus species, Micrococcus 
species), 2 blood cultures with the same antimicrobial susceptibility profile are mandatory for 
strong clinical grounds that it is not a contaminant. One example is infected material proven 
as a source for the HA-BSI.  
 
Treated in the ICU is defined as the BC has been sampled in the ICU or the patient has been 
transferred to the ICU for the treatment of the BSI.  
 
Exclusion criteria: 
Community acquired BSI = Blood culture sampled before 48 hours following hospital 
admissions. 
Patient not treated in the ICU.  
Patients that had a positive blood culture in the hospital and transferred to ICU for a different 
reason than specific treatment of the causes or consequences of HA-BSI. 
Patients less than 18 years of age. 
 
Duration of the study:  
3 consecutive months or 10 consecutive hospital-acquired bacteraemia per intensive care 
unit, whichever comes first. 
A flexible start of the inclusion period will be allowed for each ICU to facilitate participation 
in the study. 
Unit participation criteria: 
Definitions of Intensive Care vary over the world. Any department specifically designed to 
manage patients with organ failures within a health facility and able to provide invasive 
mechanical ventilation for a duration of more than 24 hours is defined as ICU for this study. 
 
 
 

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Ethical considerations. 
Eurobact 2 is a prospective observational study. All data will be collected from the patient’s 
chart. There is no requirement for any diagnostic test or intervention additional to what the 
patient is receiving s part of their treatment. 
All data will be anonymously collected on a secured webserver by the operational committee. 
No identifying data will be collected. 
Ethical requirements for data collection vary within countries and jurisdictions. Where 
appropriate, ethical approval and requirement or waiver for consent of participation will be 
obtained for each country by the country coordinator and where required by the local primary 
investigator at each site. 
 
Timeline 
• March 2018: 
o First announcement of the study. 
o A team of experts constitutes the organisational committee. 
o Country coordinators are recruited. 
o Protocol and data requirements are designed. 
o An e-crf is designed. 
• October 2018: 
o The study has been awarded the ESICM Trials Group award. 
o National Coordinators recruitment ongoing 
• November-June 
o Expressions of interest are sought from prospective participating centres 
o Ethical requirements are completed by country coordinators 
o E-CRF setup and testing 
• June 2019 
o Study commencement. 
• June 2019 – April 2020 
o Flexible 3 months commencement period 
• October 2020 
o Preliminary results presented at ESICM LIVES 2020 
o Completion of 28 days follow-up 
o Data-quality controlled and tidying-up the database. 
• Late 2020 
o Data analysis and write up of the core epidemiological description of the 
database. 
• Early 2021 
o Publication of the core paper  
o Analysis and write up of ancillary analysis. 
 
 
 

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Data to record: 
• Center data: Single entry for each participating ICU. 
o To collect adjustment variables and define center effect. 
o To define the effect of specific microbiology processing techniques on 
outcomes. 
 Type of hospital/ICU/specific recruitment 
 Staffing variables  
 Scoring systems used 
 Stewardship practices.  
• Infectious diseases specialist availability within and outside of 
the ICU.  
• Specific ID or Stewardship rounds and/or Phone advise 
• Timings (daily vs specific day vs on demand) 
• Written protocols and common practices for administration 
and modification of antimicrobial therapy (modality of 
infusion, use of TDM, MIC based adjustments) 
• Restricted antibiotics/preauthorization/use of computerized 
prescription systems 
 Microbiological lab specifics 
• Organization and communication with the ICU 
o Opening times and reporting delays 
o Communication mode (phone, internet, proprietary 
software, fax, in person, email, paper mail) 
o Techniques used  
o availability of novel rapid diagnostic techniques 
o Reporting to the clinicians and stewardship specialists 
(if different) 
 Sensitive vs resistant status 
 Reporting of MICs, resistance mechanisms, 
specific enzymes 
o Availability of TDM for each class of antibiotics and use 
of pharmacodynamic principles for dose adjustment of 
antimicrobials 
 MDR prevalence. 
 Type and frequency of screening for MDR colonisation. 
 Number of patients and severity for the study period. 
• Patient data: once per patient 
o Admission data 
 Dates of ICU and Hospital admission 
 Reason for admission 
 Co-morbid conditions 
 Severity score: APACHE II  
 Frailty and treatment limitation orders. 
o Infection data (day of bacteraemia) 
 Source  
 Severity of shock 
• SOFA score 

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• Lactate levels 
• Organ supportive therapy (MV/RRT/Vasoactive) 
 Specific / other treatments 
• steroids 
o Microbiological data 
 Center questionnaire will determine what data and timings each 
centre can provide and adjust to those 
 Date-time of sampling / positivity 
 Date-time of Gram stain / antibiogram where available 
 Rapid testing if used  
 Antibiogram / molecular methods  
 Mechanism of resistance if known 
• ESBL, CPE, MRSA, VISA, VRE 
Specific enzyme 
 MICs 
o Treatment data 
 Antibiotics already present at onset of bacteraemia 
 Antibiotics given for the infection 
• Date / time of start 
• Date / time of changes and reasons 
• Date time of stop 
• Dose / route / mode of admin (II as default, CI if used…) 
• TDM. Change of antibiotic doses based on TDM results 
o Follow up data 
 Censored at d28 
 Duration of MV/RRT/Vasoactive agents 
 SOFA score at day 7. 
 Dates of ICU and Hospital discharge 
 Vital status and cause of death 
 
Operational considerations 
 
Principal investigators 
To design the study, coordinate all actors and take primary responsibility for the conduct of 
the study. 
 
Steering (organisational) committee: 
To design the study, including protocol, data collected and scientific protocol. 
To participate in the analysis of the data and preparation of the manuscript. 
To analyse the data, results and content of the manuscript. 
 
Operational committee: 
To coordinate all actors and ensure smooth conduct of the study according to the principles 
defined in this document. They will report to the organisational committee. 
 

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National Coordinator: 
National Coordinators (NCs) will be appointed by the Organisational Committee and will 
have a key role in the conduction of the study in the individual countries as leaders of the 
project. The role/responsibilities of the NC include the following: 
• Advertise the study in the individual countries and identify participating hospitals 
and local investigators in their country. 
• Apply for regulatory approval in a national level where applicable and ensure that 
ethical committee (EC) approvals or waivers for all the participating hospitals in the 
country are in place prior to the initiation of the study. The NC will receive scanned 
copies of the EC approvals from all centers, will check them and report to the 
Principal Investigator (PI). The checked by the NC scanned copies of the EC approval 
will be sent altogether to the PI prior to the initiation of the study. 
• Assist with the translation of the study protocol/CRF where required. 
• Ensure the distribution of study material to the centers (protocol, CRF, instruction 
manuals etc.) and that the local investigators are familiar to the study material prior 
to the start date. 
• Ensure good communication with the participating sites in the respective country 
and to animate local investigators to achieve optimal recruitment and follow up 
during the period of the study. During the period of database quality control (data 
‘cleaning’) the NC should animate the individual to reply in possible queries. 
• They are invited to participate in data analysis and preparation of the manuscript. 
 
Local Primary Investigators (LPI) 
There will be one local investigator per ICU with the following role/responsibilities: 
• Lead the study in their hospital. 
• Communication with the NC and OC for each issue that may arise. 
• Apply for ethical review where applicable in accordance with the requirements for 
each jurisdiction. 
• Ensure accurate data collection and accurate and timely eCRF completion.  
• Reply promptly to possible queries during the period of database quality control  
• Maintain a patient list to match identifier codes in the database to individual patients 
in order to record clinical outcomes and supply any missing data points. 
• Guarantee the integrity, consistency and quality of data collection and ensure that 
the EC approval, the patient list and the paper CRFs will be kept in a safe and locked 
place for the period of time set in the study protocol. 
 
Electronic data capture: 
The case report file and the electronic version will follow these principles: 
• Anonymity. 
• Data security and encryption of internet communications. 
• Minimisation of the data required to answer the primary and secondary objectives. 
• Ease of use. 
• Reliability. 
Data will be collected on an electronic CRF (eCRF, secured website). The patient file or a local 
copy of the Paper/PDF versions of the center form and the patient’s CRF will be considered 
as source data. 

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Financial considerations 
A grant of 25 000 euros has been awarded by the ESICM Trials Group for operational 
management of the study and eCRF management. 
A grant of 30 000 euros has been awarded by the ESCMID for operational management of 
the study and statistical analysis. 
A grant of 5000 Australian dollars has been awarded by the Norva Dahlia foundation 
specifically to facilitate patient inclusions in Australia. 
Support will be provided in kind by the primary investigators at their institutions.  
 
Sponsor and Legal considerations 
The Outcomerea organization is the sponsor, data-custodian and responsible for data 
security, management and statistical analysis.  Where required the Outcomerea 
organization will provide with data transfer agreements between them and participating 
centres. 
Security, confidentiality and data quality processes 
All data will be collected by the LPI at each site. A list of included patients will only be kept 
locally by the LPI at each site. Confidentiality must be kept at all times and the file should be 
kept in a locked environment or digitally encrypted in a secure fashion. 
Data will be collected to a secure webserver.  
No identifying data will be transferred at any time. 
 
The eCRF will contain consistency checks to avoid typing errors and capture of implausible 
data. Efforts will be made to accommodate different unit systems and harmonise data in the 
back-end. Routine data consistency checks will be operated by the statistical team and any 
inconsistencies will be returned to the operational committee to be discussed with the NC 
and LPI. Every case report will be reviewed manually by the operational committee and 
queries discussed by the LPI. 
In extreme cases of inconsistencies and unavailable data case reports may be excluded from 
the study. 
 
Use of data and property 
The data pooled in the databank will be the collective property of the investigators and 
maintained by the Outcomerea organization and the primary investigators to be used for 
scientific purposes. 
 
An initial description of the data will be provided by the statistical team to describe the 
database and answer the primary and secondary objectives of the study. 
Any requests for subsequent analysis will be reviewed by the steering committee, on behalf 
of the investigators. Validity, overlap and scientific interests will be taken in account before 
a decision is made and a supplementary analysis is provided or not. 
Statistical analysis 
Statistical analyses will be performed using SAS (SAS institute, NC USA), R (R project Vienna 
Austria) and additional software where appropriate. Categorical variables will be described 

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as numbers and proportions. Continuous variables will be described as mean and standard 
deviation or median and inter-quartile range. Differences between groups will be described 
with the appropriate statistical test accordingly. Multivariable hierarchical models will be 
used to investigate the independent associations within collected variables and mortality.  
Models for causal inferences (propensity score or inverse probability of treatment weighting) 
will be used for the appropriate determinants of outcome.  
Rules for publication and authorship 
 
After the study and data monitoring are completed and the database has been closed, the 
statistical team will provide a comprehensive analysis. The principal investigators will prepare 
a draft manuscript and submit to the organisational committee and prospective authors for 
discussion, analysis and editing. They will form the Writing Committee.  From each submission 
a period of 2-3 weeks will be allowed for comments and discussion before a revised 
manuscript is prepared. The process is to be repeated until a satisfactory scientific manuscript 
is obtained. In case of disagreements on the scientific content, adjudication will be obtained 
by voting within prospective authors. In extreme cases adjudication will be done by the 
principal investigators. 
 
Authorship will be defined according to the guidelines published by the international 
Committee of Medical Journal Editors (ICMJE) which can be summarized in the following 4 
principles to define an author [7]. 
1. Substantial contributions to the conception or design of the work; or the acquisition, 
analysis, or interpretation of data for the work; AND 
2. Drafting the work or revising it critically for important intellectual content; AND 
3. Final approval of the version to be published; AND 
4. Agreement to be accountable for all aspects of the work in ensuring that questions 
related to the accuracy or integrity of any part of the work are appropriately 
investigated and resolved. 
Substantial coordination efforts will also be considered for authorship. 
It is expected that most members of the organization committee and country coordinators 
may fulfil the above criteria according to their contribution. 
Group authorship will be defined as “The Eurobact 2 study group”. All research publications 
will be reported as: “the authors, the Eurobact 2 study group on behalf of the infection section 
of the ESICM.” 
We will list all PI at each center as collaborators as allowed by the publishing journal. All 
collaborators will be listed in the acknowledgement section of each publication according to 
their contribution. 
Pre-Planned subgroup and ancillary analysis. 
 
• The effects of combination therapy and aminoglycosides in high severity patients. 
• Timing of source control  
 
 

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Organization 
 
Primary investigators 
Alexis Tabah 
Jean-François Timsit  
 
Steering committee, National Coordinators (NC) 
Country \  NC 
Name 
Contact 
Argentina 
NC 
Gabriela Vidal 
mariagabrielavidal@hotmail.com 
Australia 
NC 
Alexis Tabah 
atabah@gmail.com 
Australia 
 
Mahesh Ramanan 
ramanan.mahesh@gmail.com 
Australia 
 
Jeffrey Lipman 
j.lipman@uq.edu.au 
Australia 
 
Kathryn Wilks 
Kathryn.Wilks@health.qld.gov.au 
Australia 
 
Kevin Laupland 
klaupland@gmail.com 
Belgium 
NC 
Liesbet De Bus 
Liesbet.DeBus@ugent.be 
Belgium 
 
Jan de Waele 
Jan.DeWaele@UGent.be 
Brazil 
NC 
Frederico Bruzzi de 
Carvalho 
fredbruzcarv@gmail.com 
Bosnia & Herzegovina 
NC 
Pedja Kovacevic 
peko051@yahoo.com 
Bolivia 
NC 
Monica Crespo 
mcrespor81@gmail.com 
Canada 
 
Anand Kumar 
akumar61@yahoo.com 
Canada 
NC 
Wendy Sligl 
wsligl@ualberta.ca 
China 
NC 
Haibo Qiu 
haiboq2000@163.com 
Colombia 
NC 
Mario Arias 
aguilera1105@hotmail.com 
Croatia 
NC 
Ina Filipovic-Grcic 
inafg@yahoo.com 
Dubai 
NC 
Adel Alsisi 
adel_sisi75@yahoo.com 
Egypt 
NC 
Adel Alsisi 
adel_sisi75@yahoo.com 
France 
 
Jean-François Timsit  
jean-francois.timsit@aphp.fr 
France 
NC 
Marc Leone 
Marc.LEONE@ap-hm.fr 
France 
 
Etienne Ruppe 
etienne.ruppe@gmail.com 
France 
 
Stephane Ruckly 
stephane.ruckly@icuresearch.eu 
Georgia 
NC 
Vakhtang Kaloiani 
vaxtang_kaloiani@yahoo.com 
Germany 
NC 
Hendrik Bracht 
Hendrik.Bracht@uniklinik-ulm.de 
Greece 
NC 
Kostoula Arvaniti 
arvanitik@hotmail.com 
Greece 
 
Georgios Dimopoulos 
gdimop@med.uoa.gr 
Hungary 
NC 
Akos Csomos 
csomos.akos@gmail.com 
India 
NC 
Mohan Gurjar 
m.gurjar@rediffmail.com 
Italy 
NC 
Matteo Bassetti 
matteo.bassetti@asuiud.sanita.fvg.it 
Japan 
NC 
Yoshiro Hayashi 
yoshi.icu@gmail.com 
Lebanon 
NC 
Fayez Abillama 
fayez.abillama@gmail.com 
Libya 
NC 
Muhammed Elhadi 
muhammed.elhadi.uot@gmail.com 
Lithuania 
NC 
Saulius Vosylius 
saulius.vosylius@gmail.com 
Malaysia 
NC 
Helmi Sulaiman 
edenhelmi@gmail.com 
Mexico 
NC 
Silvio A. Namendys-Silva 
snamendyss@medicasur.org.mx 
Morocco 
NC 
Khalid Abidi 
abidikhalid6@gmail.com 
Netherlands 
NC 
Jeroen Schouten 
Jeroen.Schouten@radboudumc.nl 

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Nepal 
NC 
Gentle Shrestha 
gentlesunder@hotmail.com 
New Zealand 
NC 
Ross Freebairn 
ross.freebairn@gmail.com 
Nigeria 
NC 
Oyebola O. Adekola 
oyebolaadekola@yahoo.com 
Philippines 
NC 
Aaron Mark Hernandez 
aaronmark923@gmail.com 
Poland 
NC 
Adam Mikstacki 
adamiks@ump.edu.pl 
Portugal 
NC 
Jose Artur Paiva 
jarturpaiva@gmail.com 
Portugal 
 
Pedro Povoa 
pedrorpovoa@gmail.com 
Qatar 
NC 
Ali Aithssain  
a_aithssain@hotmail.com 
Republic of Ireland 
NC 
Ignacio Martin-Loeches 
drmartinloeches@gmail.com 
Republic of Korea 
NC 
Jeon Kyeongman 
kjeon@skku.edu 
Russian Federation 
NC 
Alexey Gritsan 
gritsan67@mail.ru 
South Africa 
NC 
Mervyn Mer 
Mervyn.Mer@wits.ac.za 
Spain 
NC 
Ricard Ferrer Rocca 
r.ferrer@vhebron.net 
Spain 
 
Jose Garnacho-Montero 
jgarnachom@gmail.com 
Sweden 
NC 
Fredrik Sjovall 
fredrik.sjovall@med.lu.se 
Tunisia 
NC 
Mounir Bouaziz 
mounir.bouaziz@rns.tn 
Turkey 
NC 
Murat Akova 
makova@hacettepe.edu.tr 
United Kingdom 
NC 
Andrew Conway Morris 
mozza@doctors.org.uk 
USA 
NC 
Andre Kalil 
akalil@unmc.edu 
 
Operational committee: 
Alexis Tabah 
Stephane Ruckly 
 
Data management and quality control: 
Stephane Ruckly 
Alexis Tabah 
Mahesh Ramanan 
Cheryl Fourie 
 
Statistical analysis 
Jean-François Timsit 
Stephane Ruckly 
Alexis Tabah 
 
Outcomerea is a non-profit nongovernmental organization, collaborative of researchers to 
promote and develop research and education in critical care. Outcomerea maintains the e-
rhrea multicentre database of ICU admissions and has a strong track record in ICU research. 
 
Outcomerea is the data custodian for the Eurobact II database on behalf of the investigators. 
It will provide with the CRF, data hosting and security, data management and statistical 
analysis for the Eurobact II study. 
References 
 
1.  
Singer M, Deutschman CS, Seymour C, et al (2016) The third international consensus 
definitions for sepsis and septic shock (sepsis-3). JAMA - J. Am. Med. Assoc. 315:801–

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810 
2.  
Vincent J, Rello J, Marshall J, et al (2009) International study of the prevalence and 
outcomes of infection in intensive care units. JAMA 302:2323–9 . doi: 
10.1001/jama.2009.1754 
3.  
Tabah A, Koulenti D, Laupland K, et al (2012) Characteristics and determinants of 
outcome of hospital-acquired bloodstream infections in intensive care units: The 
EUROBACT International Cohort Study. Intensive Care Med 38:1930–1945 . doi: 
10.1007/s00134-012-2695-9 
4.  
De Waele JJ, Akova M, Antonelli M, et al (2018) Antimicrobial resistance and 
antibiotic stewardship programs in the ICU: insistence and persistence in the fight 
against resistance. A position statement from ESICM/ESCMID/WAAAR round table on 
multi-drug resistance. Intensive Care Med 44:189–196 . doi: 10.1007/s00134-017-
5036-1 
5.  
Vincent J-L, Lefrant J-Y, Kotfis K, et al (2018) Comparison of European ICU patients in 
2012 (ICON) versus 2002 (SOAP). Intensive Care Med. doi: 10.1007/s00134-017-5043-
2 
6.  
Investigators TP (2017) Early, Goal-Directed Therapy for Septic Shock — A Patient-
Level Meta-Analysis. N Engl J Med 376:2223–2234 . doi: 10.1056/NEJMoa1701380 
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ICMJE (2017) Recommendations for the Conduct, Reporting, Editing, and Publication 
of Scholarly Work in Medical Journals. ICMJE 1–17 
 
 
Version record 
 
 
CRF 
1.04-15/04/2019 
Corrected typographic errors in subsections numbering.  
1.03 –28/02/2019 
Simplified admission categories to medical and surgical elective or emergency  
Clarified Co-morbidities to allow for Charlson score calculation but also APACHE II ROD. 
Re-organised scoring data to simplify data capture and avoid duplicate entry of the same 
values if cases have a date of ICU admission = date of BSI. Data captured is the same. 
Added the variables: CRP, Procalcitonin, Lymphocyte count. 
Added a section to inform on previous MDR colonisation and antibiotics received in the 7 
days prior to the index BSI. 
Clarified definitions for withhold or withdraw life-sustaining treatment. 
1.02 – 21 /01/2019   added information about antimicrobial loading dose (Yes/No).  
Added version number to footer 
1.01 – 03/01/2019 
Added details on haematological malignancies on co-morbid conditions (2.5)  
Added high flow nasal canula, levosimendan, terlipressin to severity assessment and day 7 
status (2.7, 5) 
Added neutrophil count additionally to White blood cell count that was already recorded 
(2.7, 3.5, 5) 
Added Tracheobronchitis as an option for possible sources for BSI (3.3) 
Added once daily dose as an option for antibiotic administration (4.0) 

Page 16 of 16 
Protocol v 1.06 – 19/04/2019 
Added the option of withdrawing treatment as a reason to stop the antibiotic (4.0) 
Added G-CSF, INF-γ and blood purification techniques as other treatments for sepsis (4.3) 
Added bronchoscopy as investigations (now section 4.4) 
Removed the section where the investigator could enter other pre-calculated scores as this 
is not required anymore (2.8, removed) 
Added detail to which type of ventilation (Invasive, non-invasive, high flow) to day 28 follow 
up (6). 
 
Protocol 
1.06-19/04/2019 
Added Prof. Anand Kumar (sc) and Prof. Wendy Sligl (NC) for Canada 
1.05-17/04/2019 
Added Dr. Haibo Qiu as NC for China and Dr. Alexey Gritsan as NC for the Russian Federation  
1.04- 15/04/2019 
Added Dr. Adel Alsisi as NC for Egypt and Dubai 
1.03– 28/03/2019 
Clarified the role of the Outcomerea organization as the sponsor and data custodian for the 
study. 
Mention of the ESCMID grant. 
1.02 Added Dr. Pedro Povoa to the steering committee. 
1.01 
11/01/2019 
Added Dr Ross Freebairn as NC for New Zealand. 
1.01– 03/01/2019  
Added Dr Muhammed Elhadi as a NC for Libya 
Added page numbers to protocol 
Clarified the electronic data capture requirements 
Corrected typographic errors. 
3/1/2019 : added changes to version record for CRF 
Changed file naming convention from file-date.extension to file-version.extension