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

Study Overview
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Brief Summary
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This is a prospective, observational, multicenter, case-control study.

Detailed Description
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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 To describe the treatment regimens used in subjects with 3GCR-Ec and 3GCS-Ec bacteremia. To determine the association between duration of intravenous antibiotics and Inverse Probability Weighting (IPW)-adjusted Desirability Of Outcome Ranking (DOOR) outcomes at 30 days To determine the association between total duration of antibiotics and IPW-adjusted DOOR outcomes at 30 days 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.

Official Title
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MDRO: Study of Highly Resistant Escherichia Coli

Conditions
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E Coli Infection

Intervention / Treatment
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* Other: no Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Positive monomicrobial blood culture for 3GCR-Ec (cases) or 3GCS-Ec (control) 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: Previously included in this study as either control or case subject Previous blood culture positive for E. coli during the current hospitalization In vitro non-susceptibility to any carbapenem tested in the local clinical microbiology laboratory Evidence of carbapenemase production in the E. coli isolate of interest as determined by the local clinical microbiology laboratory
Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 3GCR ceftriaxone-resistant-E. coli<br>Positive blood culture for above resistant e coli. Observational there will be no intervention | Other: no Intervention<br>* This is an observational study. There is no intervention<br>|
| 3GCS ceftriaxone-susceptible-E. coli<br>Positive blood culture for above susceptible e coli. Observational there will be no intervention | Other: no Intervention<br>* This is an observational study. There is no intervention<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Extended Spectrum β-Lactamases (ESBL)