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 CHEST November 2012; 142(5): 1200-1210
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 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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