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| ID | Type | Description | Link |
|---|---|---|---|
| UM1AI104681 | U.S. NIH Grant/Contract | View source | |
| KL2TR000136 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
| National Center for Advancing Translational Sciences (NCATS) | NIH |
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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)?
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | Experimental | Standard Mayo practices (bacterial culture and susceptibility testing) will be used. FilmArray testing will not be performed. |
|
| FilmArray test | Experimental | 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 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FilmArray testing | Device | 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. |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Length of Intensive Care Unit Stay | within 14 days of positive blood culture until ICU discharge | |
| Percentage of Patients Who Acquired Clostridium Difficile or Multidrug-resistant Organisms Within 30 Days After Enrollment | 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. |
Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robin Patel, MD | Mayo Clinic | Principal Investigator |
| Ritu Banerjee, MD, Ph.D | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic in Rochester | Rochester | Minnesota | 55905 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26197846 | Result | Banerjee R, Teng CB, Cunningham SA, Ihde SM, Steckelberg JM, Moriarty JP, Shah ND, Mandrekar JN, Patel R. Randomized Trial of Rapid Multiplex Polymerase Chain Reaction-Based Blood Culture Identification and Susceptibility Testing. Clin Infect Dis. 2015 Oct 1;61(7):1071-80. doi: 10.1093/cid/civ447. Epub 2015 Jul 20. |
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Subjects were recruited at the Mayo Clinic in Rochester, Minnesota from August 2013 to March 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | Control | Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed. |
| FG001 | FilmArray Test | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Randomized subjects were excluded if they had a positive blood culture in the prior week, had not provided the state research authorization, previously enrolled in the study, died or transitioned to comfort care within 24 hours of enrollment, or had a negative Gram stain. Only non-excluded subjects were included in the baseline characteristics.
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| ID | Title | Description |
|---|---|---|
| BG000 | Control | Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed. |
| BG001 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Subjects could have received more than one antimicrobial. Participants analyzed per variable below are expressed as (n=control, FilmArray test, and FilmArray+Stewardship) | Posted | Median | Inter-Quartile Range | hours | Approximately 4 days after enrollment |
|
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All events that occurred within 2 weeks following enrollment and were documented in the medical record were collected.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control | Standard Mayo practices (culture and susceptibility testing) will be used. FilmArray testing will not be performed. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hepatitis | Hepatobiliary disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ritu Banerjee, M.D., Ph.D. | Mayo Clinic | 507-284-6904 | banerjee.ritu@mayo.edu |
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| ID | Term |
|---|---|
| D016470 | Bacteremia |
| D016469 | Fungemia |
| D018805 | Sepsis |
| D004198 | Disease Susceptibility |
| ID | Term |
|---|---|
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
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| ID | Term |
|---|---|
| D000073602 | Antimicrobial Stewardship |
| ID | Term |
|---|---|
| D017723 | Drug Utilization Review |
| D004363 | Drug Utilization |
| D010605 | Pharmacy Administration |
| D009934 | Organization and Administration |
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|
| Antimicrobial Stewardship | Behavioral | Real time antimicrobial stewardship: an infectious diseases pharmacist or physician will provide patient-specific recommendations to modify antimicrobial therapy. |
|
| Bacterial culture | Other | This test identifies the pathogen responsible for an infection. |
|
| Susceptibility testing | Other | 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. |
|
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 |
| Approximately 30 days after positive blood culture |
| Negative Gram Stain |
|
| Non-Blood Specimens in Bottles |
|
| System/Technical Error |
|
| Lost to Follow-up |
|
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 |
| 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. |
| OG002 | 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. |
|
|
|
| Secondary | 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. | 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) | Posted | Median | Inter-Quartile Range | hours | Approximately 14 days after positive blood culture |
|
|
|
|
| Secondary | 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. | 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). | Posted | Median | Inter-Quartile Range | hours | Positive Gram stain, 96 hours after enrollment |
|
|
|
|
| Secondary | 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. | Posted | Number | Percentage of blood cultures | Within 14 days after positive blood culture |
|
|
|
|
| Secondary | Time to Pathogen Identification | 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. | Posted | Median | Inter-Quartile Range | hours | Approximately 14 days after positive blood culture |
|
|
|
|
| Secondary | Number of Subjects Who Had Negative Blood Cultures Within 3 Days After Enrollment | Posted | Number | participants | 3 Days after enrollment |
|
|
|
|
| Other Pre-specified | Length of Intensive Care Unit Stay | Posted | Median | Inter-Quartile Range | days | within 14 days of positive blood culture until ICU discharge |
|
|
|
|
| Other Pre-specified | Percentage of Patients Who Acquired Clostridium Difficile or Multidrug-resistant Organisms Within 30 Days After Enrollment | 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. | Posted | Number | percentage of participants | Approximately 30 days after positive blood culture |
|
|
|
|
| Secondary | Length of Entire Hospitalization (Days) | Posted | Median | Inter-Quartile Range | days | Participants were followed for the duration of hospital stay, approximately 15 days |
|
|
|
|
| Secondary | 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. | Posted | Number | participants | 30 days after positive blood culture |
|
|
|
|
| Secondary | 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. | Posted | Number | participants | Approximately 14 days after positive blood culture |
|
|
|
|
| Secondary | Percentage of Subjects With Infectious Disease Consultation Within 72 Hours of Enrollment | Posted | Number | percentage of participants | Approximately within 72 hours of positive blood culture |
|
|
|
| Secondary | 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. | 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. | Posted | Mean | Standard Deviation | dollars | Approximately 7 days after positive blood culture and for duration of entire hospitalization |
|
|
|
|
| 0 |
| 207 |
| 3 |
| 207 |
| EG001 | 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. | 0 | 198 | 3 | 198 |
| EG002 | 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. | 0 | 212 | 2 | 212 |
| Renal insufficiency | Renal and urinary disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Seizures | Nervous system disorders | Systematic Assessment |
|
| Prolonged QTc interval | Cardiac disorders | Systematic Assessment |
|
| Myelosuppression | Immune system disorders | Systematic Assessment |
|
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| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000072742 | Invasive Fungal Infections |
| D009181 | Mycoses |
| D020969 | Disease Attributes |
| D006298 | Health Services Administration |
| D014600 | Utilization Review |
| D011787 | Quality of Health Care |
| D011785 | Quality Assurance, Health Care |
| D017530 | Health Care Quality, Access, and Evaluation |
|
| Kruskal-Wallis |
| 0.04 |
| 2-Sided |
| No |
| Superiority or Other |
| Kruskal-Wallis |
| <0.0001 |
| 2-Sided |
| No |
| Superiority or Other |
|
| Fisher Exact |
| 0.42 |
| 2-Sided |
| No |
| Superiority or Other |
|
| Antimicrobials Costs |
|
| Kruskal-Wallis |
| 0.0006 |
| 2-Sided |
| No |
| Superiority or Other |
| Comparison between the 3 arms for antimicrobials costs. | Kruskal-Wallis | 0.6540 | 2-Sided | No | Superiority or Other |