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

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

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.

This study will be performed as a pragmatic, randomized controlled clinical trial with parallel group assignment.

In addition to usual care, patients will receive direct-from-blood testing using the T2Bacteria® Panel.

Providers will be prompted to order the T2Bacteria® Panel (direct-from-blood testing) and accompanying communications regarding panel results will be delivered.

The time between randomization and the start time for the last dose of intravenous vancomycin received by the patient within 14 days of randomization.

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.

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.)

Individual participant data that underlie the results reported will be made available (including data dictionaries) after de-identification.

The data will become available 3 months following publication of outcomes and will remain available for at least 5 years.

Data will be made available to researchers who provide a methodologically sound proposal that has been approved by the Vanderbilt Institutional Review Board and the study executive committee.

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