Rapid Identification and Susceptibility Testing of Pathogens From Blood Cultures

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01898208
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH), National Center for Advancing Translational Science (NCATS) (NIH)
• Enrollment: 743
• Location: 1
• Arms: 3
• Duration (Months): 12
• Patients Per Site Per Month: 62

Study Details

Study Description

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)?

Condition or Disease	Intervention/Treatment	Phase
Bacteremia; Fungemia; Bloodstream Infection	Device: FilmArray testing; Behavioral: Antimicrobial Stewardship; Other: Bacterial culture; Other: Susceptibility testing	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 743 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Diagnostic
• Official Title: Rapid Identification and Susceptibility Testing of Pathogens Growing in Blood Culture Bottles - A Quality Improvement Theragnostic Stewardship Project
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

4. Time to Pathogen Identification [Approximately 14 days after positive blood culture]

5. Number of Subjects Who Had Negative Blood Cultures Within 3 Days After Enrollment [3 Days after enrollment]

6. Length of Entire Hospitalization (Days) [Participants were followed for the duration of hospital stay, approximately 15 days]

7. 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.

8. 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.

9. Percentage of Subjects With Infectious Disease Consultation Within 72 Hours of Enrollment [Approximately within 72 hours of positive blood culture]

10. 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.

Other Outcome Measures

1. Length of Intensive Care Unit Stay [within 14 days of positive blood culture until ICU discharge]

2. Percentage of Patients Who Acquired Clostridium Difficile or Multidrug-resistant Organisms Within 30 Days After Enrollment [Approximately 30 days after positive blood culture]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ritu Banerjee, M.D., Ph.D., MD, Ph.D, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01898208
• Other Study ID Numbers: 11-006920; UM1AI104681; KL2TR000136
• First Posted: Jul 12, 2013
• Last Update Posted: Mar 15, 2016
• Last Verified: Feb 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Ritu Banerjee, M.D., Ph.D., MD, Ph.D, Mayo Clinic: Bacteremia; Fungemia; Bloodstream infection; susceptibility; MRSA; VRE
• Additional relevant MeSH terms: Bacteremia; Sepsis; Fungemia; Disease Susceptibility; Anti-Infective Agents; Anti-Bacterial Agents

Study Results

Participant Flow

Recruitment Details	Subjects were recruited at the Mayo Clinic in Rochester, Minnesota from August 2013 to March 2014.

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	Standard Mayo practices will be used AND FilmArray testing will be performed. Results of the FilmArray Blood Culture Infectious Disease (ID) Panel test will be communicated to the service by phone in real-time, 24 hours a day, 7 days a week.	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.
Period Title: Overall Study
STARTED	247	247	249
COMPLETED	207	198	212
NOT COMPLETED	40	49	37

Baseline Characteristics

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship	Total
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.	Total of all reporting groups
Overall Participants	207	198	212	617
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.5 (19.32)	61.4 (21.22)	61.2 (20.08)	61.4 (20.17)
Sex: Female, Male (Count of Participants)
Female	65 31.4%	82 41.4%	85 40.1%	232 37.6%
Male	142 68.6%	116 58.6%	127 59.9%	385 62.4%
Region of Enrollment (participants) [Number]
United States	207 100%	198 100%	212 100%	617 100%

Outcome Measures

1. Primary Outcome

Title	Duration of Antimicrobial Therapy (Hours)
Description	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.
Time Frame	Approximately 4 days after enrollment

Outcome Measure Data

Analysis Population Description

Subjects could have received more than one antimicrobial. Participants analyzed per variable below are expressed as (n=control, FilmArray test, and FilmArray+Stewardship)

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	207	198	212
Vancomycin (van), all subjects (n=132, 101, 124)	44	42	42
Van, organisms not requiring van (n=56, 56,57)	8.2	0	0
Van-susceptible enterococci (n=8, 8, 16)	20	70	82
Van, Methicillin-susceptible S.aureus(n=13,13,16)	23	11	8
Nafcillin, oxacillin, or cefazolin (n=20, 16, 14)	42	71	85
Piperacillin-tazobactam (n=77, 65, 72)	56	44	45
Cefepime (n=62, 52, 67	55	71	58

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	For Vancomycin, all patients
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	For vancomycin, organisms not requiring vancomycin.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.032
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	For vancomycin-susceptible enterococci
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.037
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	For vancomycin, methicillin-susceptible Staphylococcus aureus.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	For nafcillin, oxacillin, or cefazolin.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	For piperacillin-tazobactam.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	For cefepime.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	Kruskal-Wallis
	Comments

2. Secondary Outcome

Title	Time From Positive Gram Stain to First Active Antibiotic
Description	From positive Gram stain to start of active antibiotic among patients not on active therapy at enrollment; excludes subjects with contaminated blood cultures.
Time Frame	Approximately 14 days after positive blood culture

Outcome Measure Data

Analysis Population Description

Not all subjects were not on active therapy at enrollment, and also subjects with contaminated blood cultures were excluded. Participants analyzed per variable below are expressed as (n=control, FilmArray test, and FilmArray+Stewardship): (n=45, 41, 37)

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	207	198	212
Median (Inter-Quartile Range) [hours]	11	6	4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	This analysis compares the 3 groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	Kruskal-Wallis
	Comments

3. Secondary Outcome

Title	Time to First Appropriate De-escalation or First Appropriate Escalation of Antibiotics
Description	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.
Time Frame	Positive Gram stain, 96 hours after enrollment

Outcome Measure Data

Analysis Population Description

Not all subjects experienced de-escalation or escalation of their antibiotics. Participants analyzed per variable below are expressed as (n=control, FilmArray test, and FilmArray+Stewardship).

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	207	247	249
Time to first approp. de-escalation(n=121,112,111)	34	38	21
Time to first appropriate escalation (40,38,44)	24	6	5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	For time to first appropriate de-escalation comparing the 3 groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	For time to first appropriate escalation comparing the 3 groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Kruskal-Wallis
	Comments

4. Secondary Outcome

Title	Percent of Contaminated Blood Cultures Not Treated or Treated for Less Than 24 Hours
Description	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 Frame	Within 14 days after positive blood culture

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	207	198	212
Number [Percentage of blood cultures]	75	89	92

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	This analysis compares the 3 groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Time to Pathogen Identification
Time Frame	Approximately 14 days after positive blood culture

Outcome Measure Data

Analysis Population Description

The number of subjects analyzed per arm differs from the number of subjects who completed the study because this outcome measure includes only the subset of subjects who had organisms represented on the rapid multiplex PCR (rmPCR) panel.

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	169	147	165
Median (Inter-Quartile Range) [hours]	22.3	1.3	1.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test
	Comments	This analysis compares the FilmArray test to control arm.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Plus Antimicrobial Stewardship
	Comments	This analysis compares FilmArray plus antimicrobial stewardship to the control arm.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Kruskal-Wallis
	Comments

6. Secondary Outcome

Title	Number of Subjects Who Had Negative Blood Cultures Within 3 Days After Enrollment
Time Frame	3 Days after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	207	198	212
Number [participants]	147 71%	131 66.2%	146 68.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	This analysis is to compare the three groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	Kruskal-Wallis
	Comments

7. Other Pre-specified Outcome

Title	Length of Intensive Care Unit Stay
Time Frame	within 14 days of positive blood culture until ICU discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	207	198	212
Median (Inter-Quartile Range) [days]	3	2	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.90
	Comments
	Method	Kruskal-Wallis
	Comments

8. Other Pre-specified Outcome

Title	Percentage of Patients Who Acquired Clostridium Difficile or Multidrug-resistant Organisms Within 30 Days After Enrollment
Description	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.
Time Frame	Approximately 30 days after positive blood culture

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	207	198	212
Number [percentage of participants]	7.2 3.5%	8.1 4.1%	9.9 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	This analysis is a comparison of the 3 groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Chi-squared
	Comments

9. Secondary Outcome

Title	Length of Entire Hospitalization (Days)
Time Frame	Participants were followed for the duration of hospital stay, approximately 15 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	207	198	212
Median (Inter-Quartile Range) [days]	8	8	8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	This analysis compares the three groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.60
	Comments
	Method	Kruskal-Wallis
	Comments

10. Secondary Outcome

Title	All-cause and Attributable Mortality
Description	If records of death were incomplete, mortality was determined using Accurint (LexisNexis, Philadelphia, PA), an internet research and location service.
Time Frame	30 days after positive blood culture

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	207	198	212
All-cause mortality	22 10.6%	20 10.1%	18 8.5%
Attributable mortality	7 3.4%	7 3.5%	2 0.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	Comparison of the 3 groups for all-cause mortality.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	Comparison of the 3 groups for attributable mortality.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	Fisher Exact
	Comments

11. Secondary Outcome

Title	Number of Subjects With Antibiotic-Associated Toxicities/Adverse Events
Description	This included all adverse events that occurred within 2 weeks following enrollment and were documented in the medical record.
Time Frame	Approximately 14 days after positive blood culture

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	207	198	212
Number [participants]	3 1.4%	3 1.5%	2 0.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	This analysis is a comparison across all three groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.82
	Comments
	Method	Fisher Exact
	Comments

12. Secondary Outcome

Title	Percentage of Subjects With Infectious Disease Consultation Within 72 Hours of Enrollment
Time Frame	Approximately within 72 hours of positive blood culture

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	207	198	212
Number [percentage of participants]	49.8 24.1%	49 24.7%	45.3 21.4%

13. Secondary Outcome

Title	Mean Total Hospitalization, Laboratory Test, and Antimicrobials Costs Per Subject
Description	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.
Time Frame	Approximately 7 days after positive blood culture and for duration of entire hospitalization

Outcome Measure Data

Analysis Population Description

The number of subjects analyzed per arm is different than the number of subjects who completed the study because outpatients and a few subjects without final billing data available were excluded.

Arm/Group Title	Control	FilmArray Test	FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.	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.	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.
Measure Participants	191	171	182
Overall Hospitalization Costs	65,450 (128,686)	66,887 (117,832)	68,729 (134,215)
Laboratory Test Cost	5,377 (10,115)	5,680 (8,872)	5,743 (9,809)
Antimicrobials Costs	2,194 (4,175)	1,932 (3,175)	1,741 (2,748)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	Comparison between the 3 arms for total hospitalization costs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7789
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	Comparison between the 3 arms for laboratory test cost.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Control, FilmArray Test, FilmArray Plus Antimicrobial Stewardship
	Comments	Comparison between the 3 arms for antimicrobials costs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6540
	Comments
	Method	Kruskal-Wallis
	Comments

Adverse Events

Adverse Event Reporting Description	All events that occurred within 2 weeks following enrollment and were documented in the medical record were collected.
Arm/Group Title	Control		FilmArray Test		FilmArray Plus Antimicrobial Stewardship
Arm/Group Description	Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed.		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.		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.
All Cause Mortality
	Control		FilmArray Test		FilmArray Plus Antimicrobial Stewardship
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Control		FilmArray Test		FilmArray Plus Antimicrobial Stewardship
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/207 (0%)		0/198 (0%)		0/212 (0%)
Other (Not Including Serious) Adverse Events
	Control		FilmArray Test		FilmArray Plus Antimicrobial Stewardship
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/207 (1.4%)		3/198 (1.5%)		2/212 (0.9%)
Cardiac disorders
Prolonged QTc interval	0/207 (0%)	0	0/198 (0%)	0	1/212 (0.5%)	1
Hepatobiliary disorders
Hepatitis	1/207 (0.5%)	1	0/198 (0%)	0	0/212 (0%)	0
Immune system disorders
Myelosuppression	0/207 (0%)	0	0/198 (0%)	0	1/212 (0.5%)	1
Nervous system disorders
Seizures	0/207 (0%)	0	1/198 (0.5%)	1	0/212 (0%)	0
Renal and urinary disorders
Renal insufficiency	1/207 (0.5%)	1	0/198 (0%)	0	0/212 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/207 (0.5%)	1	2/198 (1%)	2	0/212 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.