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

Completed

• Conditions: E Coli Infection
• Interventions: Other: no Intervention

• Registration Number: NCT04574596
• Lead Sponsor: Duke University

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Status Verified: 2020-09
• Study First Submitted: 2020-09-09
• Study First Submitted QC: 2020-09-28
• Study First Posted: 2020-10-05
• Study Start: 2020-11-12
• Primary Completion: 2021-06-01
• Study Completion: 2021-06-01
• Last Update Submitted: 2021-07-26
• Last Update Posted: 2021-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
3GCR ceftriaxone-resistant-E. coli	no Intervention	Positive blood culture for above resistant e coli. Observational there will be no intervention
3GCS ceftriaxone-susceptible-E. coli	no Intervention	Positive blood culture for above susceptible e coli. Observational there will be no intervention

Primary Outcome Measures

Name	Time	Method
Number of participants who received oral step-down therapy	Within 30 days of culture collection	Number of participants who received oral-step down therapy for treatment of e. Coli

Secondary Outcome Measures

Name	Time	Method
Duration of antibiotics	From culture collection to 30 days post culture collection	Total duration of antibiotics
Number of participants with resolution or improvement of symptoms	30 days post culture collection	Number of participants with resolution or improvement of symptoms by 30 days
Days to discharge	culture collection through 30 days post culture collection	Days from culture collection to hospital discharge
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 three-fold or greater increase in serum creatinine from day of index culture
Number of participants with a Clostridioides difficile infection	culture collection through 30 days post culture collection	Number of participants with a Clostridioides difficile infection
Number of participants with anatomic source specific symptomatic response	30 days post culture collection	Number of participants with anatomic source specific symptomatic response
Length of stay	hospital admission through 30 days post culture collection	Days from hospital admission to hospital discharge
Number of participants with ongoing antibiotic treatment at 30 days	30 days post culture collection	Number of participants with ongoing antibiotic treatment at 30 days
Duration of intravenous antibiotics	From culture collection to 30 days post culture collection	Total duration of intravenous antibiotics
Duration of oral antibiotics	From culture collection to 30 days post culture collection	Total duration of oral antibiotics
Number of participants who received short course antibiotic therapy	From culture collection to 30 days post culture collection	Number of participants who received short-course antibiotic therapy defined as \<= 7 days of antibiotic therapy
Discharged by 30 days	culture collection through 30 days post culture collection	Discharged from the hospital by 30 days
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 new positive blood culture with E. coli within 30 days of index culture
Number of participants in the ICU on day 0, 3, 5, and 7	Days 0, 3, 5, 7	Number of participants in the ICU on day 0, 3, 5, and 7
Number of participants with a readmission within 30 days of index culture	culture collection through 30 days post culture collection	Number of participants with a readmission to the same hospital within 30 days of 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 newly required renal replacement therapy post index culture
Mortality at 30 days	culture collection through 30 days post culture collection	Mortality at 30 days
Desireability of Outcome Ranking (DOOR) outcome at 30 days	30 days post culture collection	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: 1. Alive without deleterious events; 2. Alive with 1 deleterious event; 3. Alive with 2 deleterious events; 4. Alive with 3 deleterious events; 5. Death by 30 days; The undesirable events are: * Post-culture renal failure; * Clostridioides difficile infection

Trial Locations

Locations (13)

Case Western Reserve University; 🇺🇸 Cleveland, Ohio, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States

Harbor-University of California Los Angeles Medical Center; 🇺🇸 Torrance, California, United States

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States

Ochsner Medical Center; 🇺🇸 New Orleans, Louisiana, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

University of Michigan Health System; 🇺🇸 Ann Arbor, Michigan, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Weill Cornell Medical College; 🇺🇸 New York, New York, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States