title: Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study.
abstract: Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E.
  
  
  
  A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all-cause 30 day mortality.
  
  
  
  The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rates were 90.6% with ertapenem and 75.5% with other carbapenems (P = 0.06) in the ETC and 89.8% and 82.6% (P = 0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (P = 0.01) in the ETC and 9.3% and 17.1% (P = 0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24-20.08; P = 0.58) and 1.04 (0.44-2.50; P = 0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43-3.29; P = 0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43-2.03; P = 0.86) and for the propensity-matched cohorts it was 1.05 (0.46-2.44; P = 0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems.
  
  
  
  Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock.
authors.affiliation: Unidad Clínica Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Seville, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Gutiérrez-Gutiérrez
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA Departments of Medicine, Pharmacology, Biochemistry, Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
authors.affiliation: Division of Epidemiology and Preventive Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, and National Center for Infection Control, Israel Ministry of Health, Tel Aviv, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Carmeli
authors.affiliation: University of Queensland Centre for Clinical Research, The University of Queensland, Herston, Brisbane, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Paterson
authors.affiliation: Hospital Universitari Vall d'Hebrón, Barcelona, Spain.
authors.forename: Benito
authors.initials: B
authors.lastname: Almirante
authors.affiliation: Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain, and Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Martínez
authors.affiliation: Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliver
authors.affiliation: Hospital Universitari Mútua de Terrassa, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Calbo
authors.affiliation: Hospital Universitari de Bellvitge, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Peña
authors.affiliation: Hacettepe University School of Medicine, Ankara, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Akova
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Johann
authors.initials: J
authors.lastname: Pitout
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Origüen
authors.affiliation: Department of Infectious Diseases, Hospital Ramón y Cajal-IRYCIS, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Pintado
authors.affiliation: Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: García-Vázquez
authors.affiliation: Corporacio Sanitaria Parc Taulí, Sabadell, Barcelona, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Gasch
authors.affiliation: Institut für Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Köln, Cologne, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Hamprecht
authors.affiliation: Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Prim
authors.affiliation: Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Tumbarello
authors.affiliation: Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
authors.forename: German
authors.initials: G
authors.lastname: Bou
authors.affiliation: Teaching Hospital Policlinico S. Orsola Malpighi, Bologna, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Viale
authors.affiliation: Universitätsklinikum Tübingen, Tübingen, Germany.
authors.forename: Evelina
authors.initials: E
authors.lastname: Tacconelli
authors.affiliation: Hospital Clinic, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Almela
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA.
authors.forename: Federico
authors.initials: F
authors.lastname: Pérez
authors.affiliation: Hygeia General Hospital, Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
authors.affiliation: Unidad Clínica Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Seville, Spain.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Cisneros
authors.affiliation: Division of Epidemiology and Preventive Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, and National Center for Infection Control, Israel Ministry of Health, Tel Aviv, Israel.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Schwaber
authors.affiliation: Policlinico Umberto I, University of Rome La Sapienza, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Venditti
authors.affiliation: Wits Donald Gordon Medical Centre, Johannesburg, South Africa.
authors.forename: Warren
authors.initials: W
authors.lastname: Lowman
authors.affiliation: Hospital Español, Rosario, Argentina.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Bermejo
authors.affiliation: National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Po-Ren
authors.initials: PR
authors.lastname: Hsueh
authors.affiliation: Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Mora-Rillo
authors.affiliation: Hospital Universitario Reina Sofia-IMIBIC-UCO, Córdoba, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Gracia-Ahulfinger
authors.affiliation: Unidad Clínica Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Seville, Spain Departamento de Microbiología, Universidad de Sevilla, Seville, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual
authors.affiliation: Unidad Clínica Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Seville, Spain Departamento de Medicina, Universidad de Sevilla, Seville, Spain jesusrb@us.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Rodríguez-Baño
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015780:Carbapenems / Q000627:therapeutic use*; D004755:Enterobacteriaceae / Q000201:enzymology* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D000077727:Ertapenem; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D016019:Survival Analysis; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000378:metabolism*; D047090:beta-Lactams / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D047090:beta-Lactams; D001618:beta-Lactamases; D000077727:Ertapenem