title: De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock.
abstract: OBJECTIVE
  We set out to assess the safety and the impact on in-hospital and 90-day mortality of antibiotic de-escalation in patients admitted to the ICU with severe sepsis or septic shock.
  
  
  METHODS
  We carried out a prospective observational study enrolling patients admitted to the ICU with severe sepsis or septic shock. De-escalation was defined as discontinuation of an antimicrobial agent or change of antibiotic to one with a narrower spectrum once culture results were available. To control for confounding variables, we performed a conventional regression analysis and a propensity score (PS) adjusted-multivariable analysis.
  
  
  RESULTS
  A total of 712 patients with severe sepsis or septic shock at ICU admission were treated empirically with broad-spectrum antibiotics. Of these, 628 were evaluated (84 died before cultures were available). De-escalation was applied in 219 patients (34.9%). By multivariate analysis, factors independently associated with in-hospital mortality were septic shock, SOFA score the day of culture results, and inadequate empirical antimicrobial therapy, whereas de-escalation therapy was a protective factor [Odds-Ratio (OR) 0.58; 95% confidence interval (CI) 0.36-0.93). Analysis of the 403 patients with adequate empirical therapy revealed that the factor associated with mortality was SOFA score on the day of culture results, whereas de-escalation therapy was a protective factor (OR 0.54; 95% CI 0.33-0.89). The PS-adjusted logistic regression models confirmed that de-escalation therapy was a protective factor in both analyses. De-escalation therapy was also a protective factor for 90-day mortality.
  
  
  CONCLUSIONS
  De-escalation therapy for severe sepsis and septic shock is a safe strategy associated with a lower mortality. Efforts to increase the frequency of this strategy are fully justified.
authors.affiliation: Unidad Clínica de Cuidados Críticos y Urgencias, Hospital Universitario Virgen del Rocío, Sevilla, Spain, jgarnachom@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Garnacho-Montero
authors.forename: A
authors.initials: A
authors.lastname: Gutiérrez-Pizarraya
authors.forename: A
authors.initials: A
authors.lastname: Escoresca-Ortega
authors.forename: Y
authors.initials: Y
authors.lastname: Corcia-Palomo
authors.forename: Esperanza
authors.initials: E
authors.lastname: Fernández-Delgado
authors.forename: I
authors.initials: I
authors.lastname: Herrera-Melero
authors.forename: C
authors.initials: C
authors.lastname: Ortiz-Leyba
authors.forename: J A
authors.initials: JA
authors.lastname: Márquez-Vácaro
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001419:Bacteria / Q000302:isolation & purification / Q000472:pathogenicity; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012044:Regression Analysis; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D012772:Shock, Septic / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality*; D013030:Spain / Q000453:epidemiology; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents
references.citation: Infection. 2013 Feb;41(1):203-10
references.pmid: 23254646
references.citation: Crit Care Med. 2004 Nov;32(11):2183-90
references.pmid: 15640629
references.citation: Crit Care. 2010;14(6):R225
references.pmid: 21167047
references.citation: Intensive Care Med. 2007 Aug;33(8):1369-78
references.pmid: 17558493
references.citation: Crit Care Med. 2013 Feb;41(2):580-637
references.pmid: 23353941
references.citation: Chest. 2009 Nov;136(5):1237-1248
references.pmid: 19696123
references.citation: Clin Infect Dis. 1999 Nov;29(5):1171-7
references.pmid: 10524959
references.citation: Crit Care Med. 2010 May;38(5):1276-83
references.pmid: 20308885
references.citation: J Antimicrob Chemother. 2008 Feb;61(2):436-41
references.pmid: 18056733
references.citation: Intensive Care Med. 2007 Sep;33(9):1533-40
references.pmid: 17549458
references.citation: Crit Care. 2013 Jul 12;17(4):R140
references.pmid: 23849321
references.citation: Crit Care Med. 1985 Oct;13(10):818-29
references.pmid: 3928249
references.citation: Intensive Care Med. 1993;19(5):265-72
references.pmid: 8408935
references.citation: Crit Care. 2011;15(2):R79
references.pmid: 21366903
references.citation: Cochrane Database Syst Rev. 2013 Mar 28;(3):CD007934
references.pmid: 23543557
references.citation: Crit Care Med. 2003 Dec;31(12):2742-51
references.pmid: 14668610
references.citation: Chest. 2000 Jul;118(1):146-55
references.pmid: 10893372
references.citation: Crit Care Med. 2005 Jul;33(7):1538-48
references.pmid: 16003060
references.citation: Crit Care Med. 2006 Jun;34(6):1589-96
references.pmid: 16625125
references.citation: Crit Care Med. 2003 Feb;31(2):462-7
references.pmid: 12576952
references.citation: Chest. 2003 May;123(5):1615-24
references.pmid: 12740282
references.citation: Crit Care Med. 2012 May;40(5):1404-9
references.pmid: 22430235
references.citation: Intensive Care Med. 2003 Jan;29(1):49-54
references.pmid: 12528022
references.citation: Crit Care Med. 2008 Jan;36(1):296-327
references.pmid: 18158437
references.citation: Infection. 2011 Aug;39(4):319-25
references.pmid: 21509424
references.citation: Intensive Care Med. 1996 Jul;22(7):707-10
references.pmid: 8844239
references.citation: J Infect Dis. 2008 Apr 15;197(8):1079-81
references.pmid: 18419525
references.citation: Int J Antimicrob Agents. 2010 Apr;35(4):375-81
references.pmid: 20122817
references.citation: Clin Infect Dis. 2011 Sep;53 Suppl 2:S33-55; quiz S56-8
references.pmid: 21868447
references.citation: Chest. 2006 May;129(5):1210-8
references.pmid: 16685011
references.citation: Intensive Care Med. 2010 Dec;36(12):1993-2003
references.pmid: 20689924