title: Clinical efficacy of β-lactam/β-lactamase inhibitor combinations for the treatment of bloodstream infection due to extended-spectrum β-lactamase-producing Enterobacteriaceae in haematological patients with neutropaenia: a study protocol for a retrospective observational study (BICAR).
abstract: Bloodstream infection (BSI) due to extended-spectrum β-lactamase-producing Gram-negative bacilli (ESBL-GNB) is increasing at an alarming pace worldwide. Although β-lactam/β-lactamase inhibitor (BLBLI) combinations have been suggested as an alternative to carbapenems for the treatment of BSI due to these resistant organisms in the general population, their usefulness for the treatment of BSI due to ESBL-GNB in haematological patients with neutropaenia is yet to be elucidated. The aim of the BICAR study is to compare the efficacy of BLBLI combinations with that of carbapenems for the treatment of BSI due to an ESBL-GNB in this population.
  
  
  
  A multinational, multicentre, observational retrospective study. Episodes of BSI due to ESBL-GNB occurring in haematological patients and haematopoietic stem cell transplant recipients with neutropaenia from 1 January 2006 to 31 March 2015 will be analysed. The primary end point will be case-fatality rate within 30 days of onset of BSI. The secondary end points will be 7-day and 14-day case-fatality rates, microbiological failure, colonisation/infection by resistant bacteria, superinfection, intensive care unit admission and development of adverse events.
  
  
  
  The number of expected episodes of BSI due to ESBL-GNB in the participant centres will be 260 with a ratio of control to experimental participants of 2.
  
  
  
  The protocol of the study was approved at the first site by the Research Ethics Committee (REC) of Hospital Universitari de Bellvitge. Approval will be also sought from all relevant RECs. Any formal presentation or publication of data from this study will be considered as a joint publication by the participating investigators and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). The study has been endorsed by the European Study Group for Bloodstream Infection and Sepsis (ESGBIS) and the European Study Group for Infections in Compromised Hosts (ESGICH).
authors.affiliation: Infectious Diseases Department, Bellvitge University Hospital, IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.|Duran i Reynals Hospital, ICO, L'Hospitalet de Llobregat, Barcelona, Spain.|REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Gudiol
authors.affiliation: Infectious Diseases Department, Bellvitge University Hospital, IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.|REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Royo-Cebrecos
authors.affiliation: Statistics Advisory Service, Institute of Biomedical Research of Bellvitge, Rovira i Virgili University, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Tebe
authors.affiliation: Faculty of Medicine, Instituto do Câncer do Estado de São Paulo, University of São Paulo, Sao Paulo, Brazil.
authors.forename: E
authors.initials: E
authors.lastname: Abdala
authors.affiliation: Hacettepe University School of Medicine, Ankara, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Akova
authors.affiliation: Infectious Diseases Research Group, Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC/University Hospitals Virgen del Rocio and Virgen Macarena, Seville, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Álvarez
authors.affiliation: Infectious Diseases Unit, Instituto de Investigación Hospital "12 de Octubre" (i+12), "12 de Octubre" University Hospital; School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Maestro-de la Calle
authors.affiliation: REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain.|Reina Sofía University Hospital-IMIBIC-UCO, Córdoba, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cano
authors.affiliation: University Hospital of Alberta, Edmonton, Alberta, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Cervera
authors.affiliation: Infectious Disease Consultant, Digestive Transplant Service, Hospital das Clínicas, Universidade Federal Minas Gerais, Brazil.
authors.forename: W T
authors.initials: WT
authors.lastname: Clemente
authors.affiliation: Infectious Diseases Department, Ramon y Cajal Hospital, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Martín-Dávila
authors.affiliation: Infectious Diseases Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: A
authors.initials: A
authors.lastname: Freifeld
authors.affiliation: Department of Internal Medicine, University Hospital Mútua de Terrassa, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Gómez
authors.affiliation: Department of Microbiology & Infectious Diseases, Concord Hospital, Concord, New South Wales, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Gottlieb
authors.affiliation: Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau and Instituto de Investigación Biomédica Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Gurguí
authors.affiliation: Infectious Diseases Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina.
authors.forename: F
authors.initials: F
authors.lastname: Herrera
authors.affiliation: Infectious Diseases, Hospital Rawson, San Juan, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Manzur
authors.affiliation: Department of Hematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Academic Teaching Hospital of Charité University Medical School, Berlin, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Maschmeyer
authors.affiliation: REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain.|Infectious Disease Unit, Internal Medicine Department, Barcelona Hospital, SCIAS, Barcelona, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Meije
authors.affiliation: REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain.|Infectious Diseases Unit, Cruces University Hospital, Bilbao, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Montejo
authors.affiliation: Infectious Diseases Division, Santa Maria Misericordia University Hospital, Udine, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Peghin
authors.affiliation: REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain.|Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospitals Virgen Macarena and Virgen del Rocío-IBiS; Department of Medicine, University of Seville, Seville, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Rodríguez-Baño
authors.affiliation: REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain.|Infectious Diseases Department, Vall d'Hebrón University Hospital, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Ruiz-Camps
authors.affiliation: Hospital Santa Casa de Misericórdia de Porto Alegre, Brazil.
authors.forename: T C
authors.initials: TC
authors.lastname: Sukiennik
authors.affiliation: Infectious Diseases Department, Bellvitge University Hospital, IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.|REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Carratalà
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy; D004359:Drug Therapy, Combination; D004756:Enterobacteriaceae Infections / Q000188:drug therapy*; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications*; D012189:Retrospective Studies; D015163:Superinfection / Q000517:prevention & control; D065093:beta-Lactamase Inhibitors / Q000627:therapeutic use*; D047090:beta-Lactams / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams
keywords: Bacteraemia; ESBLs; Neutropenia; beta-lactam/beta-lactamase inhibitors; haematologic stem cell transplant