title: A Systematic Review of the Definitions, Determinants, and Clinical Outcomes of Antimicrobial De-escalation in the Intensive Care Unit.
abstract: Antimicrobial de-escalation (ADE) is a strategy to reduce the spectrum of antimicrobials and aims to prevent the emergence of bacterial resistance. We present a systematic review describing the definitions, determinants and outcomes associated with ADE. We included 2 randomized controlled trials and 12 cohort studies. There was considerable variability in the definition of ADE. It was more frequently performed in patients with broad-spectrum and/or appropriate antimicrobial therapy (P= .05 to .002), when more agents were used (P= .002), and in the absence of multidrug-resistant pathogens (P< .05). Where investigated, lower or improving severity scores were consistently associated with ADE (P= .04 to <.001). The pooled effect of ADE on mortality is protective (relative risk, 0.68; 95% confidence interval, .52-.88). Because the determinants of ADE are markers of clinical improvement and/or of lower risk of treatment failure this effect on mortality cannot be retained as evidence. None of the studies were designed to investigate the effect of ADE on antimicrobial resistance.
authors.affiliation: Intensive Care Unit, Royal Brisbane and Women's Hospital.|Burns, Trauma, and Critical Care Research Centre.
authors.forename: Alexis
authors.initials: A
authors.lastname: Tabah
authors.affiliation: Intensive Care Unit, Royal Brisbane and Women's Hospital.|Burns, Trauma, and Critical Care Research Centre.|School of Pharmacy, The University of Queensland.
authors.forename: Menino Osbert
authors.initials: MO
authors.lastname: Cotta
authors.affiliation: Unidad Clínica de Cuidados Intensivos, Hospital Universitario Virgen Macarena, Instituto de Biomedicina de Sevilla, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Garnacho-Montero
authors.affiliation: Department of Intensive Care, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Schouten
authors.affiliation: Intensive Care Unit, Royal Brisbane and Women's Hospital.|Burns, Trauma, and Critical Care Research Centre.|School of Pharmacy, The University of Queensland.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Intensive Care Unit, Royal Brisbane and Women's Hospital.|Burns, Trauma, and Critical Care Research Centre.|Faculty of Health, Queensland University of Technology, Brisbane.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Melbourne EpiCentre, Royal Melbourne Hospital and Department of Medicine, University of Melbourne, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Tacey
authors.affiliation: APHP - Hopital Bichat - Reanimation Medicale et des Maladies Infectieuses.|UMR 1137 - IAME Team 5 - DeSCID: Decision Sciences in Infectious Diseases, Control and Care; Inserm/Univ Paris Diderot, Sorbonne Paris Cité.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Timsit
authors.affiliation: Service d'Anesthésie et de Réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université.
authors.forename: Marc
authors.initials: M
authors.lastname: Leone
authors.affiliation: Unité de Prévention et de Lutte Contre les Infections Nosocomiales, CHU Angers-Université D'Angers, France.
authors.forename: Jean Ralph
authors.initials: JR
authors.lastname: Zahar
authors.affiliation: Department of Critical Care Medicine, Ghent University Hospital, Belgium.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: De Waele
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D004352:Drug Resistance, Microbial; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents
keywords: de-escalation; resistance; stewardship; streamlining