Rapid Identification and Susceptibility Testing of Pathogens From Blood Cultures

Study Overview
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Brief Summary
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Would rapid identification of bacteria and rapid detection of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE) (using an FDA-cleared assay) in positive blood culture bottles improve patient care at Mayo Clinic Rochester (or just lead to increased cost)?

Detailed Description
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We hypothesize that the FilmArray Blood Culture ID Panel will reduce the duration of empiric broad-spectrum antimicrobial therapy typically administered in patients who have positive blood cultures, improving clinical outcome and reducing cost. To test this hypothesis we propose a prospective, randomized controlled study comparing outcomes among patients with positive blood cultures who receive either: Standard culture and antimicrobial susceptibility testing (AST) of positive blood culture bottles as is done today (control), standard culture and AST of positive blood culture bottles plus the FilmArray Blood Culture ID Panel (intervention group 1), or standard culture and AST of positive blood culture bottles plus the FilmArray Blood Culture ID Panel testing along with expert infectious diseases phone consultation (intervention group 2). In both intervention groups, results of the FilmArray test will be communicated by phone to the primary service, along with templated comments about optimal antimicrobial therapy, based on the result. (Templated comments will also be used in the control group). In intervention group 2, an infectious diseases pharmacist or physician will provide patient-specific recommendations to modify antimicrobial therapy, if appropriate, based on microbiology results and clinical information obtained through medical record review and discussion with the primary service.

Official Title
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Rapid Identification and Susceptibility Testing of Pathogens Growing in Blood Culture Bottles - A Quality Improvement Theragnostic Stewardship Project

Conditions
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Bacteremia, Fungemia, Bloodstream Infection

Intervention / Treatment
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* Device: FilmArray testing
* Behavioral: Antimicrobial Stewardship
* Other: Bacterial culture
* Other: Susceptibility testing


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Positive blood culture during the study period. No positive blood cultures in prior 7 days Minnesota state research authorization provided Exclusion criteria: No Minnesota state research authorization Deceased or transitioned to comfort care within 24 hours of enrollment Positive blood culture in prior 7 days Previously enrolled in this study Negative Gram stain

Ages Eligible for Study
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Maximum Age: 99 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control<br>Standard Mayo practices (bacterial culture and susceptibility testing) will be used. FilmArray testing will not be performed. | Other: Bacterial culture<br>* This test identifies the pathogen responsible for an infection.<br>Other: Susceptibility testing<br>* Antibiotic susceptibility testing determines the susceptibility of a bacterial strain to a specific antibiotic or a panel of antibiotics. Antibiotic susceptibility testing determines the susceptibility of a bacterial strain to a specific antibiotic or a panel of antibiotics.<br>|
| Experimental: FilmArray test<br>Standard Mayo practices will be used AND FilmArray testing will be performed. Results of the FilmArray Blood Culture ID Panel test will be communicated to the service by phone in real-time, 24 hours a day, 7 days a week. | Device: FilmArray testing<br>* FilmArray Blood Culture Identification (BCID) Panel is a polymerase chain reaction (PCR) panel that identifies 19 types of bacteria, 5 types of fungi, and select antimicrobial-resistance genes.<br>* Other names: FilmArray Blood Culture Identification Panel;Other: Bacterial culture<br>* This test identifies the pathogen responsible for an infection.<br>Other: Susceptibility testing<br>* Antibiotic susceptibility testing determines the susceptibility of a bacterial strain to a specific antibiotic or a panel of antibiotics. Antibiotic susceptibility testing determines the susceptibility of a bacterial strain to a specific antibiotic or a panel of antibiotics.<br>|
| Experimental: FilmArray plus antimicrobial stewardship<br>Standard Mayo practices will be used. FilmArray testing will be performed and reported as above, for intervention group 1. IN ADDITION, an expert will review the subject's FilmArray Blood Culture ID Panel result and medical record and contact the primary service if a modification of antimicrobial therapy may be appropriate. | Device: FilmArray testing<br>* FilmArray Blood Culture Identification (BCID) Panel is a polymerase chain reaction (PCR) panel that identifies 19 types of bacteria, 5 types of fungi, and select antimicrobial-resistance genes.<br>* Other names: FilmArray Blood Culture Identification Panel;Behavioral: Antimicrobial Stewardship<br>* Real time antimicrobial stewardship: an infectious diseases pharmacist or physician will provide patient-specific recommendations to modify antimicrobial therapy.<br>Other: Bacterial culture<br>* This test identifies the pathogen responsible for an infection.<br>Other: Susceptibility testing<br>* Antibiotic susceptibility testing determines the susceptibility of a bacterial strain to a specific antibiotic or a panel of antibiotics. Antibiotic susceptibility testing determines the susceptibility of a bacterial strain to a specific antibiotic or a panel of antibiotics.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Antimicrobial Therapy (Hours) | Difference between the date and time of the antibiotic start order (or Gram stain-positive blood culture, if antibiotics were started prior to the positive culture result) and the date and time of the antibiotic stop order. Shorter duration of broad spectrum antibiotics and longer duration of narrow-spectrum antibiotics were considered favorable outcomes. | Approximately 4 days after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Positive Gram Stain to First Active Antibiotic | From positive Gram stain to start of active antibiotic among patients not on active therapy at enrollment; excludes subjects with contaminated blood cultures. | Approximately 14 days after positive blood culture | 
| Time to First Appropriate De-escalation or First Appropriate Escalation of Antibiotics | De-escalation included discontinuation of 1 or more antibiotics and/or switching from a broad- to a narrow spectrum antibiotic. Escalation included initiation of 1 or more antibiotics and/or switching from a narrow- to a broad-spectrum antibiotic. | Positive Gram stain, 96 hours after enrollment | 
| Percent of Contaminated Blood Cultures Not Treated or Treated for Less Than 24 Hours | Contaminated blood cultures were defined as growth of organisms such as coagulase-negative staphylococci from a single blood culture set when greater than or equal to 2 blood culture sets were collected, except among subjects suspected to have true bacteremia associated with central venous catheters or devices. | Within 14 days after positive blood culture | 
| Time to Pathogen Identification |  | Approximately 14 days after positive blood culture | 
| Number of Subjects Who Had Negative Blood Cultures Within 3 Days After Enrollment |  | 3 Days after enrollment | 
| Length of Entire Hospitalization (Days) |  | Participants were followed for the duration of hospital stay, approximately 15 days | 
| All-cause and Attributable Mortality | If records of death were incomplete, mortality was determined using Accurint (LexisNexis, Philadelphia, PA), an internet research and location service. | 30 days after positive blood culture | 
| Number of Subjects With Antibiotic-Associated Toxicities/Adverse Events | This included all adverse events that occurred within 2 weeks following enrollment and were documented in the medical record. | Approximately 14 days after positive blood culture | 
| Percentage of Subjects With Infectious Disease Consultation Within 72 Hours of Enrollment |  | Approximately within 72 hours of positive blood culture | 
| Mean Total Hospitalization, Laboratory Test, and Antimicrobials Costs Per Subject | Costs were calculated using a standardized inflation-adjusted estimate of costs for each service or procedure performed in constant dollars. This approach adjusts for hospital-billed charges with Medicare Cost Report department-level cost-to-charge ratios. Physician services were proxied with Medicare reimbursement rates based on Current Procedure Terminology (CPT)-4 codes using the Medicare Fee Schedule. We did not include the cost of the stewardship program in the cost analysis, as it is not a billed service. As there was no Medicare reimbursement rate for the rmPCR test at the time of the study, test cost was proxied using the FilmArray respiratory panel. These costs were varied in sensitivity analysis with rmPCR test cost ranging from a 50% decrease to a 300% increase. | Approximately 7 days after positive blood culture and for duration of entire hospitalization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacteremia, Fungemia, Bloodstream infection, susceptibility, MRSA, VRE