title: The dynamics of the pulmonary microbiome during mechanical ventilation in the intensive care unit and the association with occurrence of pneumonia.
abstract: Ventilator-associated pneumonia (VAP) is the most common nosocomial infections in patients admitted to the ICU. The adapted island model predicts several changes in the respiratory microbiome during intubation and mechanical ventilation.
  
  
  
  We hypothesised that mechanical ventilation and antibiotic administration decrease the diversity of the respiratory microbiome and that these changes are more profound in patients who develop VAP.
  
  
  
  Intubated and mechanically ventilated ICU-patients were included. Tracheal aspirates were obtained three times a week. 16S rRNA gene sequencing with the Roche 454 platform was used to measure the composition of the respiratory microbiome. Associations were tested with linear mixed model analysis and principal coordinate analysis.
  
  
  
  111 tracheal aspirates were obtained from 35 patients; 11 had VAP, 18 did not have VAP. Six additional patients developed pneumonia within the first 48 hours after intubation. Duration of mechanical ventilation was associated with a decrease in α diversity (Shannon index; fixed-effect regression coefficient (β): -0.03 (95% CI -0.05 to -0.005)), but the administration of antibiotic therapy was not (fixed-effect β: 0.06; 95% CI -0.17 to 0.30). There was a significant difference in change of β diversity between patients who developed VAP and control patients for Bray-Curtis distances (p=0.03) and for Manhattan distances (p=0.04).Burkholderia, Bacillalesand, to a lesser extent,Pseudomonadalespositively correlated with the change in β diversity.
  
  
  
  Mechanical ventilation, but not antibiotic administration, was associated with changes in the respiratory microbiome. Dysbiosis of microbial communities in the respiratory tract was most profound in patients who developed VAP.
authors.affiliation: Intensive Care, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Zakharkina
authors.affiliation: Intensive Care, St James Hospital, Dublin, Ireland.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Martin-Loeches
authors.affiliation: Intensive Care, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Matamoros
authors.affiliation: Intensive Care, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Povoa
authors.affiliation: Department of Pneumology, Hospital Clinic i Provincial, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Torres
authors.affiliation: Intensive Care, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Janine B
authors.initials: JB
authors.lastname: Kastelijn
authors.affiliation: Clinical Microbiology, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Jorrit J
authors.initials: JJ
authors.lastname: Hofstra
authors.affiliation: Clinical Microbiology, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: de Wever
authors.affiliation: Department of Microbiology, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Menno
authors.initials: M
authors.lastname: de Jong
authors.affiliation: Intensive Care, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.affiliation: Critical Care Centre, Corporació Sanitària I Universitaria Parc Taulí-Hospital De Sabadell-Ciber Enfermedades Respiratorias, Sabadell, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Artigas
authors.affiliation: Intensive Care, Academic Medical Center, Amsterdam, Netherlands.|Department of Respiratory Medicine, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Lieuwe D J
authors.identifier: 0000-0003-2911-4549
authors.initials: LDJ
authors.lastname: Bos
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D064806:Dysbiosis / Q000382:microbiology; D005260:Female; D014644:Genetic Variation / Q000187:drug effects; D006801:Humans; D007362:Intensive Care Units; D007442:Intubation, Intratracheal; D008297:Male; D064307:Microbiota / Q000187:drug effects / Q000235:genetics*; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000635:transmission; D053717:Pneumonia, Ventilator-Associated / Q000382:microbiology*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012121:Respiration, Artificial / Q000009:adverse effects*; D012137:Respiratory System / Q000382:microbiology*; D014132:Trachea / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S
keywords: Bacterial Infection; Pneumonia