title: Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock.
abstract: OBJECTIVE
  Our goal was to determine the impact of the initiation of inappropriate antimicrobial therapy on survival to hospital discharge of patients with septic shock.
  
  
  METHODS
  The appropriateness of initial antimicrobial therapy, the clinical infection site, and relevant pathogens were retrospectively determined for 5,715 patients with septic shock in three countries.
  
  
  RESULTS
  Therapy with appropriate antimicrobial agents was initiated in 80.1% of cases. Overall, the survival rate was 43.7%. There were marked differences in the distribution of comorbidities, clinical infections, and pathogens in patients who received appropriate and inappropriate initial antimicrobial therapy (p < 0.0001 for each). The survival rates after appropriate and inappropriate initial therapy were 52.0% and 10.3%, respectively (odds ratio [OR], 9.45; 95% CI, 7.74 to 11.54; p < 0.0001). Similar differences in survival were seen in all major epidemiologic, clinical, and organism subgroups. The decrease in survival with inappropriate initial therapy ranged from 2.3-fold for pneumococcal infection to 17.6-fold with primary bacteremia. After adjustment for acute physiology and chronic health evaluation II score, comorbidities, hospital site, and other potential risk factors, the inappropriateness of initial antimicrobial therapy remained most highly associated with risk of death (OR, 8.99; 95% CI, 6.60 to 12.23).
  
  
  CONCLUSIONS
  Inappropriate initial antimicrobial therapy for septic shock occurs in about 20% of patients and is associated with a fivefold reduction in survival. Efforts to increase the frequency of the appropriateness of initial antimicrobial therapy must be central to efforts to reduce the mortality of patients with septic shock.
authors.affiliation: Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada; Cooper Hospital/University Medical Center, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Camden. Electronic address: akumar61@yahoo.com.
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Emergency Medicine, University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Ellis
authors.affiliation: Intensive Care Department, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
authors.forename: Yaseen
authors.initials: Y
authors.lastname: Arabi
authors.affiliation: Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Dan
authors.initials: D
authors.lastname: Roberts
authors.affiliation: Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Bruce
authors.initials: B
authors.lastname: Light
authors.affiliation: Cooper Hospital/University Medical Center, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Camden.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parrillo
authors.affiliation: Section of Critical Care Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Dodek
authors.affiliation: Critical Care Medicine, Royal Jubilee and Victoria General Hospitals, Vancouver Island Health Authority, Victoria, BC, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Wood
authors.affiliation: Biomolecular Sciences Program and Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, Canada.
authors.forename: Aseem
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Section of Infectious Diseases, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL.
authors.forename: David
authors.initials: D
authors.lastname: Simon
authors.affiliation: Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Peters
authors.affiliation: Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ahsan
authors.affiliation: Biostatistical Consulting Unit, Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Dan
authors.initials: D
authors.lastname: Chateau
mesh_terms: D000900:Anti-Bacterial Agents / Q000633:toxicity*; D015897:Comorbidity; D006801:Humans; D016017:Odds Ratio; D012189:Retrospective Studies; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality*; D015996:Survival Rate
chemical_list: D000900:Anti-Bacterial Agents