Pathobiomes in Gut of Critically Ill Patients

Обзор

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.

Вмешательства

• Другое P. aeruginosa using in vitro and in vivo assays
  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 investigators also plan 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.

Первичные конечные точки

• In vitro pyocyanin screening assay to determine if a stool sample has any virulence inducing ability on laboratory strains of P. aeruginosa [Срок оценки: Through study completion, an average of 3 years]
• In vivo C. elegans lethality model to determine if liquid media culture "spiked" with stool sample filtrate will induce a lethal phenotype in laboratory strains of P. aeruginosa [Срок оценки: Through study completion, an average of 3 years]
• PCR array analysis of known P. aeruginosa virulence genes following exposure to stool sample filtrate deemed to be highly activating by the in vitro pyocyanin assay and in vivo C. elegans lethality model. [Срок оценки: Through study completion, an average of 3 years]

Критерии участия

Критерии включения

• Any ethnicity
• Age > 18 years and < 85 years

Критерии исключения

• A known history of HIV/AIDS
• Active pregnancy
• Are incarcerated will be excluded from the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• The University of Chicago — Hyde Park

Идентификаторы

NCT: NCT06822465 · 16494B · 5R01GM062344-23

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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