title: Colonization and infection with extended-spectrum β-lactamase-producing Enterobacteriaceae in ICU patients: what impact on outcomes and carbapenem exposure?
abstract: OBJECTIVE
  It remains uncertain whether colonization and infection with ESBL-producing Enterobacteriaceae (ESBL-PE) affect the outcomes for ICU patients. Our objectives were to measure the effects of ESBL-PE carriage and infection on mortality, ICU length of stay (LOS) and carbapenem exposure in this population.
  
  
  METHODS
  A cause-specific hazard model based on prospectively collected data was built to assess the impact of ESBL-PE colonization and infection on competing risks of death and ICU discharge at day 28 in a multicentre cohort of ICU patients. Carbapenem exposure during the ICU stay was compared between infected carriers, uninfected carriers and non-carriers.
  
  
  RESULTS
  Among the 16,734 included patients, 594 (3.5%) were ESBL-PE carriers, including 98 (16.4%) with one or more ESBL-PE infections during the ICU stay. After adjustment for baseline and time-dependent confounders, ESBL-PE infections increased the probability of death at day 28 [adjusted cause-specific hazard ratio (aCSHR), 1.825, 95% CI 1.235-2.699, P = 0.0026] and the ICU LOS (aCSHR for discharge alive at day 28, 0.563, 95% CI 0.432-0.733, P < 0.0001). ESBL-PE carriage without infection extended the LOS (aCSHR, 0.623, 95% CI, 0.553-0.702, P < 0.0001), without affecting mortality (aCSHR, 0.906, 95% CI, 0.722-1.136, P = 0.3916). Carbapenem exposure increased in both infected and uninfected carriers when compared with non-carriers (627, 241 and 69 carbapenem days per 1000 patient days, respectively, P < 0.001).
  
  
  CONCLUSIONS
  ESBL-PE infections increased carbapenem consumption, LOS and day 28 mortality. ESBL-PE infections were rather infrequent in carriers; however, even ESBL-PE carriage without infection increased carbapenem exposure and delayed discharge, thereby amplifying the selective pressure and the colonization pressure in the ICU.
authors.affiliation: Medical Intensive Care Unit (ICU), La Source Hospital-CHR Orléans, Orléans, France.
authors.forename: François
authors.initials: F
authors.lastname: Barbier
authors.affiliation: UMR1137-IAME Inserm, Paris Diderot University, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Pommier
authors.affiliation: UMR1137-IAME Inserm, Paris Diderot University, Paris, France.
authors.forename: Wafa
authors.initials: W
authors.lastname: Essaied
authors.affiliation: Medical-Surgical ICU, Saint-Joseph Hospital Network, Paris, France.
authors.forename: Maïté
authors.initials: M
authors.lastname: Garrouste-Orgeas
authors.affiliation: Medical ICU, Albert Michallon University Hospital, Grenoble, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Schwebel
authors.affiliation: Department of Biostatistics, OUTCOMEREA, Bobigny, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ruckly
authors.affiliation: Surgical ICU, Antoine Béclère University Hospital, Clamart, France.
authors.forename: Anne-Sylvie
authors.initials: AS
authors.lastname: Dumenil
authors.affiliation: Medical ICU, Saint-Louis University Hospital, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Lemiale
authors.affiliation: Medical and Infectious Diseases ICU, Bichat-Claude Bernard University Hospital, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Mourvillier
authors.affiliation: Medical ICU, Avicenne University Hospital, Bobigny, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Clec'h
authors.affiliation: Medical ICU, Saint-Etienne University Hospital, Saint-Priest en Jarez, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: Darmon
authors.affiliation: Medical ICU, André Mignot Hospital, Versailles, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Laurent
authors.affiliation: Surgical ICU, Edouard Herriot University Hospital, Lyon, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Marcotte
authors.affiliation: UMR1137-IAME Inserm, Paris Diderot University, Paris, France Infection Control Unit, Bichat-Claude Bernard University Hospital, Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Lucet
authors.affiliation: Medical ICU, Gabriel Montpied University Hospital, Clermont-Ferrand, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Souweine
authors.affiliation: Infection Control Unit, Angers University Hospital, Angers, France.
authors.forename: Jean-Ralph
authors.initials: JR
authors.lastname: Zahar
authors.affiliation: UMR1137-IAME Inserm, Paris Diderot University, Paris, France Medical and Infectious Diseases ICU, Bichat-Claude Bernard University Hospital, Paris, France jean-francois.timsit@bch.aphp.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Timsit
mesh_terms: D000368:Aged; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use; D002423:Cause of Death; D003428:Cross Infection; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011159:Population Surveillance; D016016:Proportional Hazards Models; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D015780:Carbapenems; D001618:beta-Lactamases