title: The adequacy of timely empiric antibiotic therapy for ventilator-associated pneumonia: an important determinant of outcome.
abstract: OBJECTIVE
  The individual impact of timeliness vs adequacy of empiric antibiotic therapy for a clinical suspicion of ventilator-associated pneumonia (CSVAP) is unknown. Accordingly, in patients with CSVAP and timely initiation of empiric antibiotic therapy, we determined the impact of inadequate therapy (IT).
  
  
  METHODS
  Analysis of a randomized trial of CSVAP treated empirically with meropenem or meropenem plus ciprofloxacin was done. Adequate therapy (AT) was considered present if all pathogens in the index culture were sensitive to the empiric antibiotics; IT was defined as the presence of pathogens resistant to the empiric antibiotics. A priori, for Pseudomonas sp, 2 antibiotics with activity against the organisms were required for AT to be considered present.
  
  
  RESULTS
  Of 739 patients with CSVAP, 350 had positive cultures: 313 (89.4%) had AT, and 37 (10.6%), IT. The IT group had higher intensive care unit (35.1% vs 11.8%, P = .0001) and hospital mortalities (48.7% vs 19.5%, P < .0001), increased mechanical ventilation (15.8 vs 6.8 days, P = .0005), intensive care unit stay (13.5 vs 8.4 days, P = .02), and hospital stay (42.2 vs 27.9 days, P = .04). In multivariate analysis and a separate case control analysis, the odds ratio of hospital mortality with IT was 3.05 (95% confidence interval, 1.25-7.45; P = .01) and 3.00 (95% confidence interval, 1.24-7.24; P = .01), respectively.
  
  
  CONCLUSIONS
  In the context of early administration of empiric broad spectrum antibiotics for CSVAP, IT is associated with higher morbidity and mortality.
authors.affiliation: Department of Medicine, Queen's University, Kingston, Ontario, Canada. muscedej@kgh.kari.net
authors.forename: John G
authors.initials: JG
authors.lastname: Muscedere
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Shorr
authors.forename: Xuran
authors.initials: X
authors.lastname: Jiang
authors.forename: Andrew
authors.initials: A
authors.lastname: Day
authors.forename: Daren K
authors.initials: DK
authors.lastname: Heyland
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002939:Ciprofloxacin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D000077731:Meropenem; D008875:Middle Aged; D015999:Multivariate Analysis; D009864:Ontario / Q000453:epidemiology; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies; D013845:Thienamycins / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D002939:Ciprofloxacin; D000077731:Meropenem