Rapid Identification and Susceptibility Testing of Pathogens From Blood Cultures

Not Applicable

Completed

Conditions: Bloodstream Infection
Fungemia
Bacteremia

Interventions: Other: Bacterial culture
Device: FilmArray testing
Other: Susceptibility testing
Behavioral: Antimicrobial Stewardship

Registration Number: NCT01898208

Lead Sponsor: Mayo Clinic

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 743

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Susceptibility testing	Standard Mayo practices (bacterial culture and susceptibility testing) will be used. FilmArray testing will not be performed.
Control	Bacterial culture	Standard Mayo practices (bacterial culture and susceptibility testing) will be used. FilmArray testing will not be performed.
FilmArray test	FilmArray testing	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.
FilmArray test	Bacterial culture	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.
FilmArray test	Susceptibility testing	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.
FilmArray plus antimicrobial stewardship	FilmArray testing	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.
FilmArray plus antimicrobial stewardship	Bacterial culture	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.
FilmArray plus antimicrobial stewardship	Susceptibility testing	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.
FilmArray plus antimicrobial stewardship	Antimicrobial Stewardship	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.

Primary Outcome Measures

Name	Time	Method
Duration of Antimicrobial Therapy (Hours)	Approximately 4 days after enrollment	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.

Secondary Outcome Measures

Name	Time	Method
Time From Positive Gram Stain to First Active Antibiotic	Approximately 14 days after positive blood culture	From positive Gram stain to start of active antibiotic among patients not on active therapy at enrollment; excludes subjects with contaminated blood cultures.
Time to First Appropriate De-escalation or First Appropriate Escalation of Antibiotics	Positive Gram stain, 96 hours after enrollment	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.
Percent of Contaminated Blood Cultures Not Treated or Treated for Less Than 24 Hours	Within 14 days after positive blood culture	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.
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	30 days after positive blood culture	If records of death were incomplete, mortality was determined using Accurint (LexisNexis, Philadelphia, PA), an internet research and location service.
Number of Subjects With Antibiotic-Associated Toxicities/Adverse Events	Approximately 14 days after positive blood culture	This included all adverse events that occurred within 2 weeks following enrollment and were documented in the medical record.
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	Approximately 7 days after positive blood culture and for duration of entire hospitalization	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.