title: Empiric antibiotic therapy for suspected ventilator-associated pneumonia: a systematic review and meta-analysis of randomized trials.
abstract: OBJECTIVE
  To compare specific antibiotic regimens, and monotherapy vs. combination therapy, for the empirical treatment of ventilator-associated pneumonia (VAP).
  
  
  METHODS
  Meta-analysis.
  
  
  METHODS
  Medline, Embase, Cochrane register of controlled trials, study authors, and review articles.
  
  
  METHODS
  We included randomized controlled trials that evaluated empirical parenteral antibiotic regimens for adult patients with clinically suspected VAP.
  
  
  METHODS
  Two independent review groups searched the literature, extracted data, and evaluated trial quality. The primary outcome was all-cause mortality; secondary outcomes included treatment failure. Relative risks were pooled using a random effects model.
  
  
  RESULTS
  We identified 41 trials randomizing 7,015 patients and comparing 29 unique regimens. Methodological quality was low, reflecting low rates of complete follow-up (43.9%), use of a double-blinded interventional strategy (14.6%), and randomization concealment (48.6%). Overall mortality was 20.3%; treatment failure occurred in 37.4% of patients who could be evaluated microbiologically. No mortality differences were observed between any of the regimens compared. Only one of three pooled comparisons yielded a significant difference for treatment failure: The combination of ceftazidime/aminoglycoside was inferior to meropenem (two trials, relative risk 0.70, 95% confidence interval 0.53-0.93). Rates of mortality and treatment failure for monotherapy compared with combination therapy were similar (11 trials, relative risk for mortality of monotherapy 0.94, confidence interval 0.76-1.16; and relative risk of treatment failure for monotherapy 0.88, confidence interval 0.72-1.07).
  
  
  CONCLUSIONS
  Monotherapy is not inferior to combination therapy in the empirical treatment of VAP. Available data neither identify a superior empirical regimen nor conclusively conclude that available regimens result in equivalent outcomes. Larger and more rigorous trials evaluating the choice of, and even need for, empirical therapy for VAP are needed.
authors.affiliation: Department of Surgery, University of Toronto, Toronto, Ontario.
authors.forename: Mary-Anne W
authors.initials: MA
authors.lastname: Aarts
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Hancock
authors.forename: Daren
authors.initials: D
authors.lastname: Heyland
authors.forename: Robin S
authors.initials: RS
authors.lastname: McLeod
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D019348:Empiricism; D006801:Humans; D053717:Pneumonia, Ventilator-Associated / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D015163:Superinfection / Q000175:diagnosis / Q000188:drug therapy; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents