title: Attributable mortality of ICU-acquired bloodstream infections: Impact of the source, causative micro-organism, resistance profile and antimicrobial therapy.
abstract: ICU-acquired bloodstream infection (ICUBSI) in Intensive Care unit (ICU) is still associated with a high mortality rate. The increase of antimicrobial drug resistance makes its treatment increasingly challenging.
  
  
  
  We analyzed 571 ICU-BSI occurring amongst 10,734 patients who were prospectively included in the Outcomerea Database and who stayed at least 4 days in ICU. The hazard ratio of death associated with ICU-BSI was estimated using a multivariate Cox model adjusted on case mix, patient severity and daily SOFA.
  
  
  
  ICU-BSI was associated with increased mortality (HR, 1.40; 95% CI, 1.16-1.69; p = 0.0004). The relative increase in the risk of death was 130% (HR, 2.3; 95% CI, 1.8-3.0) when initial antimicrobial agents within a day of ICU-BSI onset were not adequate, versus only 20% (HR, 1.2; 95% CI, 0.9-1.5) when an adequate therapy was started within a day. The adjusted hazard ratio of death was significant overall, and even higher when the ICU-BSI source was pneumonia or unknown origin. When treated with appropriate antimicrobial agents, the death risk increase was similar for ICU-BSI due to multidrug resistant pathogens or susceptible ones. Interestingly, combination therapy with a fluoroquinolone was associated with more favorable outcome than monotherapy, whereas combination with aminoglycoside was associated with similar mortality than monotherapy.
  
  
  
  ICU-BSI was associated with a 40% increase in the risk of 30-day mortality, particularly if the early antimicrobial therapy was not adequate. Adequacy of antimicrobial therapy, but not pathogen resistance pattern, impacted attributable mortality.
authors.affiliation: Physiology Department, Cochin University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Paris Descartes University, Paris, France. Electronic address: christophe.adrie@cch.aphp.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Adrie
authors.affiliation: INSERM, IAME, UMR 1137, Team DesCID, F-75018 Paris, France; Medical-Surgical Intensive Care Unit, Saint Joseph Hospital, Paris, France.
authors.forename: Maité
authors.initials: M
authors.lastname: Garrouste-Orgeas
authors.affiliation: INSERM, IAME, UMR 1137, Team DesCID, F-75018 Paris, France.
authors.forename: Wafa
authors.initials: W
authors.lastname: Ibn Essaied
authors.affiliation: Medical Intensive Care Unit, Michallon University Hospital, Grenoble, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Schwebel
authors.affiliation: Medical ICU, Saint-Etienne University Hospital, Saint-Priest en Jarez, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Darmon
authors.affiliation: INSERM, IAME, UMR 1137, Team DesCID, F-75018 Paris, France; Medical Intensive Care Unit, Assistance Publique des Hôpitaux de Paris (AP-HP), Bichat University Hospital, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Mourvillier
authors.affiliation: INSERM, IAME, UMR 1137, Team DesCID, F-75018 Paris, France; Outcomerea Network, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ruckly
authors.affiliation: Medical-Surgical Intensive Care Unit, Antoine Béclère University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Clamart, France.
authors.forename: Anne-Sylvie
authors.initials: AS
authors.lastname: Dumenil
authors.affiliation: Medical-Surgical Intensive Care Unit, Centre hospitalier de Cayenne, Guyane, France.
authors.forename: Hatem
authors.initials: H
authors.lastname: Kallel
authors.affiliation: Medical-Intensive Care Unit, Edouard Heriot Hospital, Lyon University Hospital, Lyon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Argaud
authors.affiliation: Surgical-Intensive Care Unit, Edouard Heriot Hospital, Lyon University Hospital, Lyon, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Marcotte
authors.affiliation: Medical Intensive Care Unit, La Source Hospital - CHR Orléans, Orléans, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Barbier
authors.affiliation: Medical-Surgical Intensive Care Unit, André Mignot Hospital, Versailles-Le Chesnay, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Laurent
authors.affiliation: Medical-Surgical Intensive Care Unit, Gonesse Hospital, Gonesse, France.
authors.forename: Dany
authors.initials: D
authors.lastname: Goldgran-Toledano
authors.affiliation: INSERM, IAME, UMR 1137, Team DesCID, F-75018 Paris, France; Medical Intensive Care Unit, Assistance Publique des Hôpitaux de Paris (AP-HP), Avicenne University Hospital, Bobigny, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Clec'h
authors.affiliation: Medical Intensive Care Unit, Saint-Louis University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.affiliation: Medical Intensive Care Unit, Gabriel Montpied University Hospital, Clermont-Ferrand, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Souweine
authors.affiliation: INSERM, IAME, UMR 1137, Team DesCID, F-75018 Paris, France; Medical Intensive Care Unit, Assistance Publique des Hôpitaux de Paris (AP-HP), Bichat University Hospital, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Timsit
mesh_terms: D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality* / Q000517:prevention & control; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality* / Q000517:prevention & control; D016208:Databases, Factual; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005602:France / Q000453:epidemiology; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology / Q000401:mortality; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones
keywords: Antimicrobial therapy; Bloodstream infection; Nosocomial; Outcome