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

MDRO: Study of Highly Resistant Escherichia Coli

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

Study Overview

• Status: Completed
• Conditions: E Coli Infection
• Intervention / Treatment: Other: no Intervention

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• United States
  • California
    • Torrance, California, United States, 90502
      • Harbor-University of California Los Angeles Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Louisiana
    • New Orleans, Louisiana, United States, 21287
      • Ochsner Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina At Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44106-7282
      • Case Western Reserve University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

• Sample size: 300 total: 150 3GCR-Ec cases, 150 3GCS-Ec controls.
• This is a consecutive cohort study without age or gender exclusions. Special populations such as women, children, and minorities will be included.
• The study population will be drawn from subjects who are hospitalized at participating study hospitals.
• This observational study is minimal-risk and will be performed under a waiver of consent and HIPAA.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
3GCR ceftriaxone-resistant-E. coli; Positive blood culture for above resistant e coli. Observational there will be no intervention	Other: no Intervention; This is an observational study. There is no intervention
3GCS ceftriaxone-susceptible-E. coli; Positive blood culture for above susceptible e coli. Observational there will be no intervention	Other: no Intervention; This is an observational study. There is no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of antibiotics	Total duration of antibiotics	From culture collection to 30 days post culture collection
Duration of intravenous antibiotics	Total duration of intravenous antibiotics	From culture collection to 30 days post culture collection
Duration of oral antibiotics	Total duration of oral antibiotics	From culture collection to 30 days post culture collection
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
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
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
Number of participants with anatomic source specific symptomatic response	Number of participants with anatomic source specific symptomatic response	30 days post culture collection
Discharged by 30 days	Discharged from the hospital by 30 days	culture collection through 30 days post culture collection
Days to discharge	Days from culture collection to hospital discharge	culture collection through 30 days post culture collection
Length of stay	Days from hospital admission to hospital discharge	hospital admission through 30 days post culture collection
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
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
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
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
Number of participants with a Clostridioides difficile infection	Number of participants with a Clostridioides difficile infection	culture collection through 30 days post culture collection
Mortality at 30 days	Mortality at 30 days	culture collection through 30 days post culture collection
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibiotic resistance phenotype	Antibiotic resistance phenotype	Day 0, which is the date of culture collection in this observational study
Antimicrobial resistance genes	Antimicrobial resistance genes	Day 0, which is the date of culture collection in this observational study
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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Director: Vance G. Fowler, MD, Duke Clinical Research Institute; Principal Investigator: David van Duin, MD, PhD, University of North Carolina

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 12, 2020
• Primary Completion (ACTUAL): June 1, 2021
• Study Completion (ACTUAL): June 1, 2021

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (ACTUAL): October 5, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Extended Spectrum β-Lactamases (ESBL)
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Escherichia coli Infections
• Other Study ID Numbers: Pro00106280; UM1AI104681 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No