Pathobiomes in Gut of Critically Ill Patients

NCT06822465 | Recruiting

• 2 other identifiers: 16494B5R01GM062344-23
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pseudomonas Aeruginosa

Outcome Measures

Primary Outcomes (3)

• In vitro pyocyanin screening assay to determine if a stool sample has any virulence inducing ability on laboratory strains of P. aeruginosa

  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

  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.

  Through study completion, an average of 3 years

Study Arms (1)

Critically Ill Patients

All patients admitted to the burn intensive care unit (BICU), surgical intensive care unit (SICU), and the medical intensive care unit (MICU) longer than 24 hours at University of Chicago Medical Center

Other: P. aeruginosa using in vitro and in vivo assays

Interventions

P. aeruginosa using in vitro and in vivo assays OTHER

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.

Critically Ill Patients

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients admitted to the burn intensive care unit (BICU), surgical intensive care unit (SICU), and the medical intensive care unit (MICU) longer than 24 hours at University of Chicago Medical Center and are expected to have a prolonged course of care will be recruited into the study.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Chicago: lead
• National Institutes of Health (NIH): collaborator
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

The University of Chicago

Hyde Park, Illinois, 60637, United States

RECRUITING

MeSH Terms

Conditions

Pseudomonas Infections

Interventions

In Vitro Techniques

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Investigative Techniques

Study Officials

• John Alverdy, MD FACS FSIS

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Alverdy, MD FACS FSIS

CONTACT

773-702-4876; jalverdy@bsd.uchicago.edu

Leila Yazdanbakhsh, MSCI

CONTACT

773-834-5087; leila.yazdanbakhsh@bsd.uchicago.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2025
• First Posted: February 12, 2025
• Study Start: December 19, 2024
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: February 2, 2026

Record last verified: 2026-01

Locations

US (1)