Multi-Drug Resistant Organism (MDRO): Study of Highly Resistant Escherichia Coli

E Coli Infection Clinical Trial

— SHREC  

Official title:

MDRO: Study of Highly Resistant Escherichia Coli

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04574596
• Other study ID #: Pro00106280
• Secondary ID: UM1AI104681
• Status: Completed
• Start date: November 12, 2020
• Est. completion date: June 1, 2021

Study information

• Verified date: September 2020
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a prospective, observational, multicenter, case-control study.

Description:

This is an observational cohort study. A total of 300 subjects will be enrolled. Cases are defined as unique subjects who have a monomicrobial blood culture positive for growth of 3rd Generation Cephalosporin Resistant Escherichia coli (3GCR-Ec), defined as resistance to ceftriaxone or cefotaxime, during hospitalization. For each case, the next available unique subject from the same study site, with a monomicrobial blood culture positive for growth of 3rd Generation Cephalosporin Sensitive Escherichia coli (3GCS-Ec) during hospitalization will be included as a control. A waiver of informed consent and HIPAA will be requested. This is a minimal risk study without any direct subject contact. In addition, no subject information will be collected that is not part of routine clinical care.

The trigger for enrollment in the study will be the identification in a participating local microbiology laboratory of a 3GCR-Ec in a monomicrobial blood culture. These will be reported to study personnel at the study site, who will evaluate eligibility. If the subject is deemed eligible, the 3GCR-Ec isolate will be saved for shipping to the Laboratory Center, and the isolate also saved at the local laboratory. Sites will be advised to destroy any samples saved at the local laboratory as part of this study at the end of the study. The local microbiology laboratory, or designee, will then identify the next subject available with a 3GCS-Ec in a blood culture. These will also be reported to study personnel for evaluation of eligibility as a control. If the control subject is eligible, the corresponding 3GCS-Ec isolate will be saved for shipping to the Laboratory Center, and the isolate will also be saved at the local laboratory . Sites will be advised to destroy any samples saved at the local laboratory as part of this study at the end of the study.

For cases and controls, clinical data will be collected from the electronic health records (EHR) for up to 30 days after the index blood culture. Data collection will be performed by study personnel at the site into a central, secure, research database.

One E. coli isolate per study subject will be collected from the index blood culture. No other biologic samples will be collected. Data will be entered at or after the 30-day time point. There will be no long-term follow-up for subjects.

Primary Objective:

To evaluate the use of oral step down therapy in subjects with 3GCR-Ec and 3GCS-Ec bacteremia.

Secondary Objectives

1. To describe the treatment regimens used in subjects with 3GCR-Ec and 3GCS-Ec bacteremia.

2. To determine the association between duration of intravenous antibiotics and Inverse Probability Weighting (IPW)-adjusted Desirability Of Outcome Ranking (DOOR) outcomes at 30 days

3. To determine the association between total duration of antibiotics and IPW-adjusted DOOR outcomes at 30 days

4. To determine risk factors on days 0, 3, 5, and 7 after first positive blood culture for poor outcomes (either DOOR composite score or individual outcomes) at 30 days.

Exploratory Objective:

• To describe phenotypic and genotypic characteristics of bacterial isolates.

This study is minimal risk to study participants, and has no data safety monitoring board.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: June 1, 2021
• Est. primary completion date: June 1, 2021
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion criteria:

1. Positive monomicrobial blood culture for 3GCR-Ec (cases) or 3GCS-Ec (control)

2. Hospitalized at the time of obtaining index blood culture OR in the emergency department at the time of obtaining index blood culture, if followed by hospitalization within 72 hours

Exclusion criteria:

1. Previously included in this study as either control or case subject

2. Previous blood culture positive for E. coli during the current hospitalization

3. In vitro non-susceptibility to any carbapenem tested in the local clinical microbiology laboratory

4. Evidence of carbapenemase production in the E. coli isolate of interest as determined by the local clinical microbiology laboratory

Related Conditions & MeSH terms

• E Coli Infection
• Escherichia coli Infections

Intervention

Other:
• no Intervention
This is an observational study. There is no intervention

Locations

Country	Name	City	State
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Case Western Reserve University	Cleveland	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Weill Cornell Medical College	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Harbor-University of California Los Angeles Medical Center	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Antibiotic resistance phenotype	Antibiotic resistance phenotype	Day 0, which is the date of culture collection in this observational study
Other	Antimicrobial resistance genes	Antimicrobial resistance genes	Day 0, which is the date of culture collection in this observational study
Other	Duration of individual antibiotics and specific combinations of antibiotics	Duration of individual antibiotics and specific combinations of antibiotics	culture collection through 30 days post culture collection
Primary	Number of participants who received oral step-down therapy	Number of participants who received oral-step down therapy for treatment of e. Coli	Within 30 days of culture collection
Secondary	Duration of antibiotics	Total duration of antibiotics	From culture collection to 30 days post culture collection
Secondary	Duration of intravenous antibiotics	Total duration of intravenous antibiotics	From culture collection to 30 days post culture collection
Secondary	Duration of oral antibiotics	Total duration of oral antibiotics	From culture collection to 30 days post culture collection
Secondary	Number of participants who received short course antibiotic therapy	Number of participants who received short-course antibiotic therapy defined as <= 7 days of antibiotic therapy	From culture collection to 30 days post culture collection
Secondary	Number of participants with ongoing antibiotic treatment at 30 days	Number of participants with ongoing antibiotic treatment at 30 days	30 days post culture collection
Secondary	Number of participants with resolution or improvement of symptoms	Number of participants with resolution or improvement of symptoms by 30 days	30 days post culture collection
Secondary	Number of participants with anatomic source specific symptomatic response	Number of participants with anatomic source specific symptomatic response	30 days post culture collection
Secondary	Discharged by 30 days	Discharged from the hospital by 30 days	culture collection through 30 days post culture collection
Secondary	Days to discharge	Days from culture collection to hospital discharge	culture collection through 30 days post culture collection
Secondary	Length of stay	Days from hospital admission to hospital discharge	hospital admission through 30 days post culture collection
Secondary	Number of participants with a readmission within 30 days of index culture	Number of participants with a readmission to the same hospital within 30 days of index culture	culture collection through 30 days post culture collection
Secondary	Number of participants with a new positive blood culture with E. coli within 30 days of index culture	Number of participants with a new positive blood culture with E. coli within 30 days of index culture	culture collection through 30 days post culture collection
Secondary	Number of participants with a three-fold or greater increase in serum creatinine from day of index culture	Number of participants with a three-fold or greater increase in serum creatinine from day of index culture	culture collection through 30 days post culture collection
Secondary	Number of participants with a newly required renal replacement therapy post index culture	Number of participants with a newly required renal replacement therapy post index culture	culture collection through 30 days post culture collection
Secondary	Number of participants with a Clostridioides difficile infection	Number of participants with a Clostridioides difficile infection	culture collection through 30 days post culture collection
Secondary	Mortality at 30 days	Mortality at 30 days	culture collection through 30 days post culture collection
Secondary	Number of participants in the ICU on day 0, 3, 5, and 7	Number of participants in the ICU on day 0, 3, 5, and 7	Days 0, 3, 5, 7
Secondary	Desireability of Outcome Ranking (DOOR) outcome at 30 days	The desirability of outcome ranking (DOOR) in this study will assess three deleterious events (lack of clinical response, unsuccessful discharge, and undesirable events) in addition to survival at 30 days after the index culture. The five ordered levels of the variable, from best to worst, are: Alive without deleterious events; Alive with 1 deleterious event; Alive with 2 deleterious events; Alive with 3 deleterious events; Death by 30 days; The undesirable events are: Post-culture renal failure; Clostridioides difficile infection	30 days post culture collection