title: Pseudomonas aeruginosa-catecholamine inotrope interactions: a contributory factor in the development of ventilator-associated pneumonia?
abstract: BACKGROUND
  Ventilated patients receiving intensive care are at significant risk of acquiring a ventilator-associated pneumonia that is associated with significant morbidity and mortality. Despite intensive research, it is still unclear why Pseudomonas aeruginosa, a microbe that rarely causes pneumonia outside of intensive care, is responsible for so many of these infections.
  
  
  METHODS
  We investigated whether medications frequently prescribed to patients in the ICU, the catecholamine inotropes, were affecting the growth and virulence of P aeruginosa . Effects of clinically attainable concentrations of inotropes on P aeruginosa pathogenicity were explored using in vitro growth and virulence assays and an ex vivo model of infection using ciliated human respiratory epithelium.
  
  
  RESULTS
  We found that inotropes were potent stimulators of P aeruginosa growth, producing upto 50-fold increases in bacterial numbers via a mechanism involving inotrope delivery of transferrin-ron,internalization of the inotrope, and upregulation of the key pseudomonal siderophore pyoverdine.Inotropes also markedly increased biofilm formation on endotracheal tubing and enhanced the biofilm production and toxicity of P aeruginosa in its interaction with respiratory epithelium.Importantly, catecholamine inotropes also facilitated the rapid recovery of P aeruginosa from tobramycin antibiotic challenge. We also tested out the effect of the inotropes vasopressin and phenylephrine on the growth and virulence of P aeruginosa and found that, in contrast to the catecholamines,these drugs had no stimulatory effect.
  
  
  CONCLUSIONS
  Collectively, our results suggest that catecholamine inotrope-bacterial interactions may be an unexpected contributory factor to the development of P aeruginosa -ventilator-associated pneumonia.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester School of Medicine, Leicester, England.
authors.forename: Primrose P
authors.initials: PP
authors.lastname: Freestone
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester School of Medicine, Leicester, England; Division of Child Health, Leicester, England; Institute of Lung Health, Leicester, England.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hirst
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester School of Medicine, Leicester, England.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Sandrini
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester School of Medicine, Leicester, England.
authors.forename: Fathima
authors.initials: F
authors.lastname: Sharaff
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester School of Medicine, Leicester, England.
authors.forename: Helen
authors.initials: H
authors.lastname: Fry
authors.affiliation: Electron Microscopy Laboratory, University of Leicester, Leicester, England.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hyman
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester School of Medicine, Leicester, England; Division of Child Health, Leicester, England; Institute of Lung Health, Leicester, England. Electronic address: j.varma@ucl.ac.uk.
authors.forename: Chris
authors.initials: C
authors.lastname: O'Callaghan
mesh_terms: D000704:Analysis of Variance; D018441:Biofilms; D002395:Catecholamines / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity*; D012307:Risk Factors; D014774:Virulence
chemical_list: D002395:Catecholamines