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|Title:||Pseudomonas aeruginosa-Catecholamine Inotrope Interactions: A Contributory Factor in the Development of Ventilator Associated Pneumonia?|
|Abstract:||Abstract BACKGROUND:Ventilated patients on 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. RESULTS:We took a novel approach and investigated whether medications frequently prescribed to intensive care patients, 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. 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, internalisation of the inotrope, and up-regulation of the key pseudomonal siderophore pyoverdine. Inotropes also markedly increased biofilm formation on endotracheal tubing as well as enhancing 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 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 for the development of P. aeruginosa-ventilator-associated pneumonia.|
|Appears in Collections:||Published Articles, Dept. of Infection, Immunity and Inflammation|
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