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Chest. 2012 Nov;142(5):1200-1210. doi: 10.1378/chest.11-2614.

Pseudomonas aeruginosa-catecholamine inotrope interactions: a contributory factor in the development of ventilator-associated pneumonia?

Author information

1
Department of Infection, Immunity and Inflammation, University of Leicester School of Medicine, Leicester, England.
2
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.
3
Electron Microscopy Laboratory, University of Leicester, Leicester, England.
4
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.

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.

PMID:
22556319
DOI:
10.1378/chest.11-2614
[Indexed for MEDLINE]

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