The impact of mixed or polymicrobial flora in the development of ventilator-associated pneumonia.

Pneumonia is one of the most common causes of hospital-acquired infections with mortality rates reaching higher than 30%. One in 3 patients receiving mechanical ventilation develop ventilator-associated pneumonia (VAP). Despite this high incidence and mortality, the disease pathogenesis of VAP remains poorly understood. Pseudomonas aeruginosa and Staphylococcus aureus are the most common causes of VAP, and when present together, cause mortality rates of up to 50%. Recent work in our laboratory has revealed an immunosuppressive role of mechanical ventilation that likely plays a role in VAP pathogenesis. Inspired by these data – as well as a growing body of evidence that polymicrobial flora is an important cause of immunosuppression in sepsis and some other infection-related conditions, and that VAP is polymicrobial even though one or two organisms predominate – we intend to test the hypothesis that polymicrobial flora in lungs could also cause local immunosuppression and that, together with MV-induced immunosuppression, leads to growth of pathogenic bacteria in the causation of VAP. Besides this, we also intend to dissect any immunosuppressive role of Staphylococcus spp. in VAP pathogenesis as these organisms are known to have an immune-modulatory role and are frequently (co)-cultured from VAP patients. Lastly, we intend to pinpoint key interactions between P. aeruginosa and S. aureus in a humanized immune context, that together with other objectives could reveal important, and perhaps targetable steps in the pathogenesis of VAP.

Keywords:VENTILATOR ASSOCIATED PNEUMONIA

Disciplines:Inflammation, Bacteriology, Infectious diseases