Clinical Research Directory

Pathobiomes in Gut of Critically Ill Patients

Sponsor: University of Chicago

Summary

Despite powerful antibiotics, 50% of the intestinal tracts of critically ill surgical patients are colonized by Pseudomonas aeruginosa, whose mere presence in this site increases mortality fourfold by mechanisms that remain unknown. Many patients who survive the initial surgical trauma still succumb to multi-organ failure and septicemia secondary to an invasive nosocomial infection. The sequelae of shock, hypoxia, and parental nutrition result in injury to the intestinal mucosa, changes in gut permeability, and failure of intestinal defense mechanisms. These conditions put patients at risk for infection and multiple organ failure secondary to the translocation of enteric bacteria, initiating a systemic release of inflammatory mediators-a process that has been termed gut-derived sepsis. Intestinal P. aeruginosa senses host factors released during stress and responds by activating its virulence gene machinery. As such, the presence of a highly activating intestinal milieu serves to induce virulence in strains of P. aeruginosa and this correlates to the severity of a patient's illness. While the host-pathogen interaction is a dynamic process, the study expects that as a patient's illness worsens or resolves over time, the "virulence-activating" properties of their intestinal milieu will change accordingly. This study will conduct a prospective observational trial in a population of critically ill patients at the Universtiy of Chicago Medical Center. This trial will entail collecting and screening stool samples obtained from critically ill patients for their virulence inducing capabilities on laboratory strains of P. aeruginosa using in vitro and in vivo assays. The study also plans to isolate strains of intestinal P. aeruginosa from stool samples to determine the prevalence of intestinal P. aeruginosa in a population of critically ill patients.

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