title: Determinants and impact of multidrug antibiotic resistance in pathogens causing ventilator-associated-pneumonia.
abstract: BACKGROUND
  The idea that multidrug resistance (MDR) to antibiotics in pathogens causing ventilator-associated pneumonia (VAP) is an independent risk factor for adverse outcome is still debated. We aimed to identify the determinants of MDR versus non-MDR microbial aetiology in VAP and assessed whether MDR versus non-MDR VAP was independently associated with increased 30-day mortality.
  
  
  METHODS
  We performed a retrospective analysis of a prospectively registered cohort of adult patients with microbiologically confirmed VAP, diagnosed at a university hospital intensive care unit during a three-year period. Determinants of MDR as compared with non-MDR microbial aetiology and impact of MDR versus non-MDR aetiology on mortality were investigated using multivariate logistic and competing risk regression analysis.
  
  
  RESULTS
  MDR pathogens were involved in 52 of 192 episodes of VAP (27%): methicillin-resistant Staphylococcus aureus in 12 (6%), extended-spectrum beta-lactamase producing Enterobacteriaceae in 28 (15%), MDR Pseudomonas aeruginosa and other non-fermenting pathogens in 12 (6%). Multivariable logistic regression identified the Charlson index of comorbidity (odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08 to 1.75, p = 0.01) and previous exposure to more than two different antibiotic classes (OR = 5.11, 95% CI = 1.38 to 18.89, p = 0.01) as predictors of MDR aetiology. Thirty-day mortality after VAP diagnosis caused by MDR versus non-MDR was 37% and 20% (p = 0.02), respectively. A multivariate competing risk regression analysis showed that renal replacement therapy before VAP (standardised hazard ratio (SHR) = 2.69, 95% CI = 1.47 to 4.94, p = 0.01), the Charlson index of comorbidity (SHR = 1.21, 95% CI = 1.03 to 1.41, p = 0.03) and septic shock on admission to the intensive care unit (SHR = 1.86, 95% CI = 1.03 to 3.35, p = 0.03), but not MDR aetiology of VAP, were independent predictors of mortality.
  
  
  CONCLUSIONS
  The risk of MDR pathogens causing VAP was mainly determined by comorbidity and prior exposure to more than two antibiotics. The increased mortality of VAP caused by MDR as compared with non-MDR pathogens was explained by more severe comorbidity and organ failure before VAP.
authors.affiliation: Department of Intensive Care, Ghent University Hospital, De Pintelaan 185, B-9000 Gent, Belgium. pieter.depuydt@ugent.be
authors.forename: Pieter O
authors.initials: PO
authors.lastname: Depuydt
authors.forename: Dominique M
authors.initials: DM
authors.lastname: Vandijck
authors.forename: Maarten A
authors.initials: MA
authors.lastname: Bekaert
authors.forename: Johan M
authors.initials: JM
authors.lastname: Decruyenaere
authors.forename: Stijn I
authors.initials: SI
authors.lastname: Blot
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Vogelaers
authors.forename: Dominique D
authors.initials: DD
authors.lastname: Benoit
mesh_terms: D000368:Aged; D001530:Belgium / Q000453:epidemiology; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D053717:Pneumonia, Ventilator-Associated / Q000209:etiology* / Q000382:microbiology / Q000401:mortality; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors