title: Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis.
abstract: BACKGROUND
  Septic shock represents the major cause of infection-associated mortality in the intensive care unit. The possibility that combination antibiotic therapy of bacterial septic shock improves outcome is controversial. Current guidelines do not recommend combination therapy except for the express purpose of broadening coverage when resistant pathogens are a concern.
  
  
  OBJECTIVE
  To evaluate the therapeutic benefit of early combination therapy comprising at least two antibiotics of different mechanisms with in vitro activity for the isolated pathogen in patients with bacterial septic shock.
  
  
  METHODS
  Retrospective, propensity matched, multicenter, cohort study.
  
  
  METHODS
  Intensive care units of 28 academic and community hospitals in three countries between 1996 and 2007.
  
  
  METHODS
  A total of 4662 eligible cases of culture-positive, bacterial septic shock treated with combination or monotherapy from which 1223 propensity-matched pairs were generated.
  
  
  RESULTS
  The primary outcome of study was 28-day mortality. Using a Cox proportional hazards model, combination therapy was associated with decreased 28-day mortality (444 of 1223 [36.3%] vs. 355 of 1223 [29.0%]; hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; p = .0002). The beneficial impact of combination therapy applied to both Gram-positive and Gram-negative infections but was restricted to patients treated with beta-lactams in combination with aminoglycosides, fluoroquinolones, or macrolides/clindamycin. Combination therapy was also associated with significant reductions in intensive care unit (437 of 1223 [35.7%] vs. 352 of 1223 [28.8%]; odds ratio, 0.75; 95% confidence interval, 0.63-0.92; p = .0006) and hospital mortality (584 of 1223 [47.8%] vs. 457 of 1223 [37.4%]; odds ratio, 0.69; 95% confidence interval, 0.59-0.81; p < .0001). The use of combination therapy was associated with increased ventilator (median and [interquartile range], 10 [0-25] vs. 17 [0-26]; p = .008) and pressor/inotrope-free days (median and [interquartile range], 23 [0-28] vs. 25 [0-28]; p = .007) up to 30 days.
  
  
  CONCLUSIONS
  Early combination antibiotic therapy is associated with decreased mortality in septic shock. Prospective randomized trials are needed.
authors.affiliation: Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada. akumar61@yahoo.com
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
authors.forename: Ryan
authors.initials: R
authors.lastname: Zarychanski
authors.forename: Bruce
authors.initials: B
authors.lastname: Light
authors.forename: Joseph
authors.initials: J
authors.lastname: Parrillo
authors.forename: Dennis
authors.initials: D
authors.lastname: Maki
authors.forename: Dave
authors.initials: D
authors.lastname: Simon
authors.forename: Denny
authors.initials: D
authors.lastname: Laporta
authors.forename: Steve
authors.initials: S
authors.lastname: Lapinsky
authors.forename: Paul
authors.initials: P
authors.lastname: Ellis
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Mirzanejad
authors.forename: Greg
authors.initials: G
authors.lastname: Martinka
authors.forename: Sean
authors.initials: S
authors.lastname: Keenan
authors.forename: Gordon
authors.initials: G
authors.lastname: Wood
authors.forename: Yaseen
authors.initials: Y
authors.lastname: Arabi
authors.forename: Daniel
authors.initials: D
authors.lastname: Feinstein
authors.forename: Aseem
authors.initials: A
authors.lastname: Kumar
authors.forename: Peter
authors.initials: P
authors.lastname: Dodek
authors.forename: Laura
authors.initials: L
authors.lastname: Kravetsky
authors.forename: Steve
authors.initials: S
authors.lastname: Doucette
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D012189:Retrospective Studies; D012772:Shock, Septic / Q000188:drug therapy* / Q000382:microbiology; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents