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

Clostridium Difficile Clinical Trial

— DYNAMITE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06258551
• Other study ID #: PRO00035528
• Secondary ID: 1P01AI152999-01
• Status: Recruiting
• Start date: December 8, 2020
• Est. completion date: June 2026

Study information

• Verified date: February 2024
• Source: The Methodist Hospital Research Institute
• Contact: Cesar A Arias, MD, PhD, Msc
• Phone: 346-238-4870
• Email: CAArias[@]Houstonmethodist.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Antibiotic Resistant Infection
• Bacterial Infections
• Carbapenem-Resistant Enterobacteriaceae Infection
• Clostridium Difficile
• Communicable Diseases
• Enterobacteriaceae Infections
• Extended Spectrum Beta-Lactamase Producing Bacteria Infection
• Infections
• Vancomycin Resistant Enterococci Infection
• Vancomycin-Resistant Enterococcal Infection

Locations

Country	Name	City	State
United States	Houston Methodist Hospital	Houston	Texas
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas

Sponsors (7)

Lead Sponsor	Collaborator
The Methodist Hospital Research Institute	Baylor College of Medicine, M.D. Anderson Cancer Center, National Institute of Allergy and Infectious Diseases (NIAID), The University of Texas Health Science Center, Houston, University of Houston, William Marsh Rice University

Country where clinical trial is conducted

United States, 

References & Publications (7)

Caballero S, Carter R, Ke X, Susac B, Leiner IM, Kim GJ, Miller L, Ling L, Manova K, Pamer EG. Distinct but Spatially Overlapping Intestinal Niches for Vancomycin-Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae. PLoS Pathog. 2015 Sep 3;11(9):e1005132. doi: 10.1371/journal.ppat.1005132. eCollection 2015 Sep. — View Citation

Evans SR, Rubin D, Follmann D, Pennello G, Huskins WC, Powers JH, Schoenfeld D, Chuang-Stein C, Cosgrove SE, Fowler VG Jr, Lautenbach E, Chambers HF. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis. 2015 Sep 1;61(5):800-6. doi: 10.1093/cid/civ495. Epub 2015 Jun 25. Erratum In: Clin Infect Dis. 2023 Jan 6;76(1):182. — View Citation

Lee KH, Han SH, Yong D, Paik HC, Lee JG, Kim MS, Joo DJ, Choi JS, Kim SI, Kim YS, Park MS, Kim SY, Yoon YN, Kang S, Jeong SJ, Choi JY, Song YG, Kim JM. Acquisition of Carbapenemase-Producing Enterobacteriaceae in Solid Organ Transplantation Recipients. Transplant Proc. 2018 Dec;50(10):3748-3755. doi: 10.1016/j.transproceed.2018.01.058. — View Citation

Satlin MJ, Chavda KD, Baker TM, Chen L, Shashkina E, Soave R, Small CB, Jacobs SE, Shore TB, van Besien K, Westblade LF, Schuetz AN, Fowler VG Jr, Jenkins SG, Walsh TJ, Kreiswirth BN. Colonization With Levofloxacin-resistant Extended-spectrum beta-Lactamase-producing Enterobacteriaceae and Risk of Bacteremia in Hematopoietic Stem Cell Transplant Recipients. Clin Infect Dis. 2018 Nov 13;67(11):1720-1728. doi: 10.1093/cid/ciy363. — View Citation

Taur Y, Xavier JB, Lipuma L, Ubeda C, Goldberg J, Gobourne A, Lee YJ, Dubin KA, Socci ND, Viale A, Perales MA, Jenq RR, van den Brink MR, Pamer EG. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2012 Oct;55(7):905-14. doi: 10.1093/cid/cis580. Epub 2012 Jun 20. — View Citation

Ulrich RJ, Santhosh K, Mogle JA, Young VB, Rao K. Is Clostridium difficile infection a risk factor for subsequent bloodstream infection? Anaerobe. 2017 Dec;48:27-33. doi: 10.1016/j.anaerobe.2017.06.020. Epub 2017 Jun 29. — View Citation

van Duin D, Lok JJ, Earley M, Cober E, Richter SS, Perez F, Salata RA, Kalayjian RC, Watkins RR, Doi Y, Kaye KS, Fowler VG Jr, Paterson DL, Bonomo RA, Evans S; Antibacterial Resistance Leadership Group. Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis. 2018 Jan 6;66(2):163-171. doi: 10.1093/cid/cix783. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Impact of Colonization on Clinical Outcomes Using DOOR Analysis	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.	30 days
Secondary	Additional Clinical Predictors of Negative Outcomes	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.	30 days

External Links

•   Centers for Disease Control and Prevention Antimicrobial Resistance Threats Report
•   World Health Organization Antimicrobial Resistance Fact Sheet