title: Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic resistance in ICU patients: a retrospective observational study.
abstract: OBJECTIVE
  Antibiotic de-escalation is promoted to limit prolonged exposure to broad-spectrum antibiotics, but proof that it prevents the emergence of resistance is lacking. We evaluated determinants of antibiotic de-escalation in an attempt to assess whether the latter is associated with a lower emergence of antimicrobial resistance.
  
  
  METHODS
  Antibiotic treatments, starting with empirical beta-lactam prescriptions, were prospectively documented during 2013 and 2014 in a tertiary intensive care unit (ICU) and categorized as continuation, de-escalation or escalation of the empirical antimicrobial treatment. Determinants of the de-escalation or escalation treatments were identified by multivariate logistic regression; the continuation category was used as the reference group. Using systematically collected diagnostic and surveillance cultures, we estimated the cumulative incidence of antimicrobial resistance following de-escalation or continuation of therapy, with adjustment for ICU discharge and death as competing risks.
  
  
  RESULTS
  Of 478 anti-pseudomonal antibiotic prescriptions, 42 (9 %) were classified as escalation of the antimicrobial treatment and 121 (25 %) were classified as de-escalation, mainly through replacement of the originally prescribed antibiotics with those having a narrower spectrum. In multivariate analysis, de-escalation was associated with the identification of etiologic pathogens (p < 0.001). The duration of the antibiotic course in the ICU in de-escalated versus continued prescriptions was 8 (range 6-10) versus 5 (range 4-7) days, respectively (p < 0.001). Mortality did not differ between patients in the de-escalation and continuation categories. The cumulative incidence estimates of the emergence of resistance to the initial beta-lactam antibiotic on day 14 were 30.6 and 23.5 % for de-escalation and continuation, respectively (p = 0.22). For the selection of multi-drug resistant pathogens, these values were 23.5 (de-escalation) and 18.6 % (continuation) respectively (p = 0.35).
  
  
  CONCLUSIONS
  The emergence of antibiotic-resistant bacteria after exposure to anti-pseudomonal beta-lactam antibiotics was not lower following de-escalation.
authors.affiliation: Department of Critical Care Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. liesbet.debus@ugent.be.
authors.forename: Liesbet
authors.initials: L
authors.lastname: De Bus
authors.affiliation: Department of Critical Care Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Denys
authors.affiliation: Department of Critical Care Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Catteeuw
authors.affiliation: Department of Critical Care Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: Gadeyne
authors.affiliation: Department of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Ghent, Belgium.
authors.forename: Karel
authors.initials: K
authors.lastname: Vermeulen
authors.affiliation: Department of Laboratory Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Jerina
authors.initials: J
authors.lastname: Boelens
authors.affiliation: Department of Laboratory Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Claeys
authors.affiliation: Department of Critical Care Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: De Waele
authors.affiliation: Department of Critical Care Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Decruyenaere
authors.affiliation: Department of Critical Care Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.|Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
authors.forename: Pieter O
authors.initials: PO
authors.lastname: Depuydt
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002442:Ceftazidime / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000187:drug effects*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010878:Piperacillin / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D012189:Retrospective Studies; D013845:Thienamycins / Q000627:therapeutic use; D047090:beta-Lactams / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D047090:beta-Lactams; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D002442:Ceftazidime; D000077731:Meropenem; D010878:Piperacillin
keywords: Antibiotic stewardship; Beta-lactam antibiotics; De-escalation; Information technology system; Multi-drug resistance