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Original Research: Critical Care |

Pseudomonas aeruginosa-Catecholamine Inotrope InteractionsPseudomonas aeruginosa, Inotropes, and Pneumonia: A Contributory Factor in the Development of Ventilator-Associated Pneumonia?

Primrose P. Freestone, PhD; Robert A. Hirst, PhD; Sara M. Sandrini, PhD; Fathima Sharaff, MSc; Helen Fry, MD; Stefan Hyman; Chris O’Callaghan, DM, PhD
Author and Funding Information

From the Department of Infection, Immunity and Inflammation (Drs Freestone, Hirst, Sandrini, Fry, and O’Callaghan and Ms Sharaff), University of Leicester School of Medicine; the Division of Child Health (Drs Hirst and O’Callaghan); and the Electron Microscopy Laboratory (Mr Hyman), University of Leicester; and the Institute of Lung Health (Drs Hirst and O’Callaghan), Leicester, England.

Correspondence to: Chris O’Callaghan, DM, PhD, Department of Respiratory Medicine, Portex Unit, Institute of Child Health, University College London (UCL), 30 Guildford St, London, WC1N 1EH, England; e-mail: j.varma@ucl.ac.uk


Funding/Support: Drs Freestone, Sandrini, and O’Callaghan are funded by the SPARKS Children’s Charity (www.sparks.org.uk), England [Grant 09 LCS 01].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(5):1200-1210. doi:10.1378/chest.11-2614
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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 up to 50-fold increases in bacterial numbers via a mechanism involving inotrope delivery of transferrin-iron, 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.

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