Dynamics of Colonization and Infection by Multidrug-Resistant Pathogens in Immunocompromised and Critically Ill Patients

Recruiting

• Conditions: Carbapenem Resistant Bacterial Infection; Clostridium Difficile; Carbapenem-Resistant Enterobacteriaceae Infection; Extended Spectrum Beta-Lactamase Producing Bacteria Infection; Vancomycin Resistant Enterococci Infection; Antimicrobial Drug Resistance; Antibiotic Resistant Infection; Vancomycin-Resistant Enterococcal Infection

• Registration Number: NCT06258551
• Lead Sponsor: The Methodist Hospital Research Institute

Brief Summary

The goal of this observational study is to investigate how bacterial populations from the intestine and mouth of patients change during the hospitalization period and evaluate if some populations of specific bacteria increase or decrease the risk of acquiring an infection or becoming colonized by pathogenic bacteria. Participants will have the following samples collected during enrollment: stool samples (maximum 2x/week), blood draws (1x/week), oral swab (1x/week).

Detailed Description

The objectives of this study are to dissect the main microbial, clinical, and antimicrobial resistance determinants that impact colonization and infection by vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Clostridium difficile; to evaluate the role of commensal microbiota in VRE, ESBL-E/CRE, and C. difficile colonization, and to define the functional aspects of keystone microbiota and mechanisms of protection against colonization/infection.

Patients will be recruited from both intensive care units (n=500) and stem cell transplant units (n=500) and will be followed until discharge from these units, or for a maximum of four weeks. In addition to stool, blood, and oral samples, enrolled patients will have clinical data collected by chart review to evaluate colonization/infection-related clinical status, microbiological laboratory information, exposure to antibiotics, and clinical outcomes. Positive clinical cultures taken during the course of hospitalization will also be collected for analysis.

Study Timeline

• Study Start: 2020-12-08
• Status Verified: 2024-02
• Study First Submitted: 2024-02-06
• Study First Submitted QC: 2024-02-06
• Last Update Submitted: 2024-02-06
• Study First Posted: 2024-02-14
• Last Update Posted: 2024-02-14
• Primary Completion: 2026-06
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

• Admission to an intensive care unit or stem cell transplant unit (for allogeneic stem cell transplantation) within previous 24 hours

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Exclusion Criteria

• <18 years of age
• Pregnancy
• History of inflammatory bowel disease (Crohn's disease, ulcerative colitis)
• Gastrointestinal derivation (colostomy, ileostomy, etc.)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Impact of Colonization on Clinical Outcomes Using DOOR Analysis	30 days	A desirability of outcome ranking (DOOR) algorithm will be used to analyze the impact of colonization by any target organism (CRE/ESBL-E, VRE, or C. difficile) on 30 day clinical outcomes. DOOR outcomes will be ranked as follows: 1) alive without infection, 2) alive with infection, or 3) dead.

Secondary Outcome Measures

Name	Time	Method
Additional Clinical Predictors of Negative Outcomes	30 days	Separate univariable logistic regression models will be used to evaluate associations between each individual component of the DOOR outcome (i.e., mortality and clinical infection) and the type of colonization as well as other independent predictors of mortality (e.g., neutropenia, hemodialysis, Pitt score, among others). Variables with p \< 0.10 in bivariate analysis will also be included in the logistic models to assess for independent associations with outcome.

Trial Locations

Locations (2)

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States