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Rapid Identification and Susceptibility Testing of Pathogens From Blood Cultures

This study has been completed.
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
National Center for Advancing Translational Science (NCATS)
Information provided by (Responsible Party):
Ritu Banerjee, M.D., Ph.D., Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01898208
First received: July 8, 2013
Last updated: February 17, 2016
Last verified: February 2016
  Purpose
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)?

Condition Intervention
Bacteremia
Fungemia
Bloodstream Infection
Device: FilmArray testing
Behavioral: Antimicrobial Stewardship
Other: Bacterial culture
Other: Susceptibility testing

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Diagnostic
Official Title: Rapid Identification and Susceptibility Testing of Pathogens Growing in Blood Culture Bottles - A Quality Improvement Theragnostic Stewardship Project

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Duration of Antimicrobial Therapy (Hours) [ Time Frame: Approximately 4 days after enrollment ] [ Designated as safety issue: No ]
    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:
  • Time From Positive Gram Stain to First Active Antibiotic [ Time Frame: Approximately 14 days after positive blood culture ] [ Designated as safety issue: No ]
    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 [ Time Frame: Positive Gram stain, 96 hours after enrollment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 14 days after positive blood culture ] [ Designated as safety issue: No ]
    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 [ Time Frame: Approximately 14 days after positive blood culture ] [ Designated as safety issue: No ]
  • Number of Subjects Who Had Negative Blood Cultures Within 3 Days After Enrollment [ Time Frame: 3 Days after enrollment ] [ Designated as safety issue: No ]
  • Length of Entire Hospitalization (Days) [ Time Frame: Participants were followed for the duration of hospital stay, approximately 15 days ] [ Designated as safety issue: No ]
  • All-cause and Attributable Mortality [ Time Frame: 30 days after positive blood culture ] [ Designated as safety issue: No ]
    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 [ Time Frame: Approximately 14 days after positive blood culture ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Approximately within 72 hours of positive blood culture ] [ Designated as safety issue: No ]
  • Mean Total Hospitalization, Laboratory Test, and Antimicrobials Costs Per Subject [ Time Frame: Approximately 7 days after positive blood culture and for duration of entire hospitalization ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Length of Intensive Care Unit Stay [ Time Frame: within 14 days of positive blood culture until ICU discharge ] [ Designated as safety issue: No ]
  • Percentage of Patients Who Acquired Clostridium Difficile or Multidrug-resistant Organisms Within 30 Days After Enrollment [ Time Frame: Approximately 30 days after positive blood culture ] [ Designated as safety issue: No ]
    Multidrug-resistant organisms included vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, extended-spectrum cephalosporin-resistant Enterobacteriaceae, and Pseudomonas aeruginosa and Acinetobacter species resistant to greater than or equal to 3 antibiotic classes.


Enrollment: 743
Study Start Date: August 2013
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Control
Standard Mayo practices (bacterial culture and susceptibility testing) will be used. FilmArray testing will not be performed.
Other: Bacterial culture
This test identifies the pathogen responsible for an infection.
Other: Susceptibility testing
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.
Experimental: FilmArray test
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
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.
Other Name: FilmArray Blood Culture Identification Panel
Other: Bacterial culture
This test identifies the pathogen responsible for an infection.
Other: Susceptibility testing
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.
Experimental: FilmArray plus 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.
Device: FilmArray testing
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.
Other Name: FilmArray Blood Culture Identification Panel
Behavioral: Antimicrobial Stewardship
Real time antimicrobial stewardship: an infectious diseases pharmacist or physician will provide patient-specific recommendations to modify antimicrobial therapy.
Other: Bacterial culture
This test identifies the pathogen responsible for an infection.
Other: Susceptibility testing
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.

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.
  Eligibility

Ages Eligible for Study:   up to 99 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01898208

Locations
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Institute of Allergy and Infectious Diseases (NIAID)
National Center for Advancing Translational Science (NCATS)
Investigators
Principal Investigator: Robin Patel, MD Mayo Clinic
Principal Investigator: Ritu Banerjee, MD, Ph.D Mayo Clinic
  More Information

Publications:
Responsible Party: Ritu Banerjee, M.D., Ph.D., MD, Ph.D, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01898208     History of Changes
Other Study ID Numbers: 11-006920  UM1AI104681  KL2TR000136 
Study First Received: July 8, 2013
Results First Received: December 2, 2015
Last Updated: February 17, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Mayo Clinic:
Bacteremia
Fungemia
Bloodstream infection
susceptibility
MRSA
VRE

Additional relevant MeSH terms:
Disease Susceptibility
Bacteremia
Fungemia
Disease Attributes
Pathologic Processes
Bacterial Infections
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Mycoses
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 27, 2016