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

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.

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

• 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.