title: EUropean prospective cohort study onEnterobacteriaceaeshowing REsistance to CArbapenems (EURECA): a protocol of a European multicentre observational study.
abstract: The rapid worldwide spread of carbapenem-resistantEnterobacteriaceae(CRE) constitutes a major challenge. The aim of the EUropean prospective cohort study onEnterobacteriaceaeshowing REsistance to CArbapenems (EURECA), which is part of the Innovative Medicines Initiative Joint Undertaking (IMI JU) funded COMBACTE-CARE project, is to investigate risk factors for and outcome determinants of CRE infections to inform randomised clinical trial designs and to provide a historical cohort that could eventually be used for future comparisons with new drugs targeting CRE.
  
  
  
  A multicentre (50 sites), multinational (11 European countries), analytical observational project was designed, comprising 3 studies. The aims of study 1 (a prospective cohort study) include characterising the features, clinical management and outcomes of hospitalised patients with intra-abdominal infection, pneumonia, complicated urinary tract infections and bloodstream infections caused by CRE (202 patients in each group). The main outcomes will be 30-day all-cause mortality and clinical response. Study 2 (a nested case-control study) will identify the risk factors for target infections caused by CRE; 248 selected patients from study 1 will be matched with patients with carbapenem-susceptibleEnterobacteriaceae(1:1) and with hospitalised patients (1:3) and will provide a historical cohort of patients with CRE infections. Study 3 (a matched cohort study) will follow patients in study 2 in order to assess mortality, length of stay and hospital costs associated with CRE. All patients will be followed for 30 days. Different, up-to-date statistical methods will be applied to come to unbiased estimates for all 3 studies.
  
  
  
  Before-study sites will be initiated, approval will be sought from appropriate regulatory agencies and local Ethics Committees of Research or Institutional Review Boards (IRBs) to conduct the study in accordance with regulatory requirements. This is an observational study and therefore no intervention in the diagnosis, management or treatment of the patients will be required on behalf of the investigation. Any formal presentation or publication of data collected from this study will be considered as a joint publication by the participating physician(s) and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE) for authorship.
  
  
  
  NCT02709408.
authors.affiliation: Instituto de Biomedicina de Sevilla, IBiS-Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla, Seville, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Gutiérrez-Gutiérrez
authors.affiliation: Instituto de Biomedicina de Sevilla, IBiS-Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla, Seville, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Sojo-Dorado
authors.affiliation: Instituto de Biomedicina de Sevilla, IBiS-Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla, Seville, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Bravo-Ferrer
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Nienke
authors.initials: N
authors.lastname: Cuperus
authors.affiliation: Infection Control Program, Geneva University Hospitals, Genève, Switzerland.
authors.forename: Marlieke
authors.initials: M
authors.lastname: de Kraker
authors.affiliation: Faculty of Medicine, Department of Medical Microbiology, University of Antwerp, Antwerp, Belgium.|Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Tomislav
authors.initials: T
authors.lastname: Kostyanev
authors.affiliation: National Institute of Public Health of Kosovo and Faculty of Medicine, University of Prishtina, Prishtina, Serbia.
authors.forename: Lul
authors.initials: L
authors.lastname: Raka
authors.affiliation: National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Daikos
authors.affiliation: Institute of Statistics, Ulm University, Ulm, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Feifel
authors.affiliation: Paediatric Infectious Diseases Research Group, St George's University of London, London, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Folgori
authors.affiliation: Instituto de Biomedicina de Sevilla, IBiS-Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla, Seville, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual
authors.affiliation: Faculty of Medicine, Department of Medical Microbiology, University of Antwerp, Antwerp, Belgium.|Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.affiliation: AstraZeneca, Cheshire, UK.
authors.forename: Seamus
authors.initials: S
authors.lastname: O'Brien
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
authors.affiliation: Instituto de Biomedicina de Sevilla, IBiS-Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla, Seville, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Rodríguez-Baño
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D015780:Carbapenems; D016022:Case-Control Studies; D002423:Cause of Death; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D005060:Europe; D006760:Hospitalization; D006801:Humans; D059413:Intraabdominal Infections / Q000188:drug therapy* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009026:Mortality; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D011446:Prospective Studies; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems
keywords: antimicrobial therapy; carbapenem-resistance; complicated intraabdominal infections; complicated urinary tract infections; healthcare-associated pneumonia; outcome