Clinical trial NCT04574596: Multi-Drug Resistant Organism (MDRO): Study of Highly Resistant Escherichia Coli
Official title: MDRO: Study of Highly Resistant Escherichia Coli
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: E Coli Infection
Keywords: Extended Spectrum β-Lactamases (ESBL)
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2020-10-05
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants who received oral step-down therapy
timeFrame: Within 30 days of culture collection
Secondary outcomes:
measure: Duration of antibiotics
timeFrame: From culture collection to 30 days post culture collection
measure: Duration of intravenous antibiotics
timeFrame: From culture collection to 30 days post culture collection
measure: Duration of oral antibiotics
timeFrame: From culture collection to 30 days post culture collection
measure: Number of participants who received short course antibiotic therapy
timeFrame: From culture collection to 30 days post culture collection
measure: Number of participants with ongoing antibiotic treatment at 30 days
timeFrame: 30 days post culture collection
measure: Number of participants with resolution or improvement of symptoms
timeFrame: 30 days post culture collection
measure: Number of participants with anatomic source specific symptomatic response
timeFrame: 30 days post culture collection
measure: Discharged by 30 days
timeFrame: culture collection through 30 days post culture collection
measure: Days to discharge
timeFrame: culture collection through 30 days post culture collection
measure: Length of stay
timeFrame: hospital admission through 30 days post culture collection
measure: Number of participants with a readmission within 30 days of index culture
timeFrame: culture collection through 30 days post culture collection
measure: Number of participants with a new positive blood culture with E. coli within 30 days of index culture
timeFrame: culture collection through 30 days post culture collection
measure: Number of participants with a three-fold or greater increase in serum creatinine from day of index culture
timeFrame: culture collection through 30 days post culture collection
measure: Number of participants with a newly required renal replacement therapy post index culture
timeFrame: culture collection through 30 days post culture collection
measure: Number of participants with a Clostridioides difficile infection
timeFrame: culture collection through 30 days post culture collection
measure: Mortality at 30 days
timeFrame: culture collection through 30 days post culture collection
measure: Number of participants in the ICU on day 0, 3, 5, and 7
timeFrame: Days 0, 3, 5, 7
measure: Desireability of Outcome Ranking (DOOR) outcome at 30 days
timeFrame: 30 days post culture collection
Other outcomes:
measure: Antibiotic resistance phenotype
timeFrame: Day 0, which is the date of culture collection in this observational study
measure: Antimicrobial resistance genes
timeFrame: Day 0, which is the date of culture collection in this observational study
measure: Duration of individual antibiotics and specific combinations of antibiotics
timeFrame: culture collection through 30 days post culture collection
Locations:
city: Torrance
country: United States
facility: Harbor-University of California Los Angeles Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: Duke Clinical Research Institute
name: Vance G. Fowler, MD
role: STUDY_DIRECTOR
affiliation: University of North Carolina
name: David van Duin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: