Effect of Direct-from-blood Bacterial Testing on Antibiotic Administration and Clinical Outcomes

Study Overview
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Brief Summary
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Bacterial blood stream infections are common and life-threatening. Bloodstream infections have historically been identified using blood cultures, which often take 24-72 hours to result and are imperfectly sensitive. Early administration of antimicrobial therapy is a fundamental component of the management of adults presenting to the hospital with a suspected bloodstream infection and/or sepsis. But because blood cultures frequently take 24-72 hours to result, patients are typically treated with empiric, broad spectrum antibiotics. In a meta-analysis of sepsis studies, empirical antibiotic therapy was inappropriate for the organism that ultimately grew in culture in almost half of patients. Thus, patients are commonly exposed to unnecessary antibiotics without evidence of infection or with evidence of infection requiring narrow antibiotic selection. For example, current guidelines recommend the use of empiric intravenous vancomycin as coverage for a bloodstream infection caused by the bacterial pathogen methicillin-resistant S. aureus (MRSA). Vancomycin requires careful monitoring due to its narrow therapeutic range and high risk of toxicity. Administration of vancomycin to patients who do not have MRSA can lead to avoidable adverse drug events and costs, as well as drive antimicrobial resistance. There has been increasing interest in using rapid diagnostic tests that identify bacteria directly from whole blood samples without relying on growth in culture, referred to as direct-from-blood tests, to guide early therapeutic management of patients with suspected bloodstream infections in addition to standard blood cultures. One such FDA-approved, direct-from-blood test is the T2Bacteria® Panel. This panel's performance as a direct-from blood test for bacterial pathogens has been described in previous studies. A recent meta-analysis of largely observational studies reported a faster transition to targeted microbial therapy and de-escalation of empirical microbial therapy, as well as a shorter duration of intensive care unit stay and hospital stay for patients who received this direct-from-blood test. We will conduct a pragmatic, randomized clinical trial examining the effect of using the T2Bacteria® Panel direct from-blood testing, compared to using blood cultures alone (standard of care), on antimicrobial receipt and clinical outcomes for adults presenting to the hospital with suspected infection and who have been initiated on empiric therapy with intravenous vancomycin.

Official Title
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Effect of Direct-from-blood Bacterial Testing on Antibiotic Administration and Clinical Outcomes: A Learning Healthcare Pragmatic Randomized Trial

Conditions
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Bloodstream Infection, Sepsis Bacterial, MRSA Bacteremia, Vancomycin

Intervention / Treatment
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* Other: T2Bacteria® Panel (direct-from-blood testing)
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is located in the Emergency Department at Vanderbilt University Hospital ≤ 12 hours from patient presentation to the Emergency Department at Vanderbilt University Hospital Age ≥ 18 years Clinician has ordered blood cultures Clinician has ordered intravenous vancomycin Exclusion Criteria: Patient is known to be a prisoner Patient is known to be pregnant Patient is known to have received more than one dose of intravenous vancomycin within the previous 14 days Patient is known to have a positive bacterial culture in the previous 7 days Patient is known to have an infection for which at least 7 days of intravenous vancomycin would routinely be administered regardless of bacterial testing results (e.g., skin and soft tissue infection, etc.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study will be performed as a pragmatic, randomized controlled clinical trial with parallel group assignment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual Care<br>Patients will receive blood cultures and will not receive direct-from-blood testing. | Other: Usual Care<br>* Standard blood cultures.<br>|
| Active Comparator: Direct-from-blood testing<br>In addition to usual care, patients will receive direct-from-blood testing using the T2Bacteria® Panel. | Other: T2Bacteria® Panel (direct-from-blood testing)<br>* Providers will be prompted to order the T2Bacteria® Panel (direct-from-blood testing) and accompanying communications regarding panel results will be delivered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to last dose of intravenous vancomycin | The time between randomization and the start time for the last dose of intravenous vancomycin received by the patient within 14 days of randomization. | Baseline to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to last dose of systemic anti-pseudomonal beta-lactam antibiotic | The time between randomization and start time of the last dose of systemic anti-pseudomonal beta-lactam antibiotic received by the patient within 14 days of randomization. | Baseline to 14 days |