Rapid Identification and Susceptibility Testing of Pathogens From Blood Cultures

Bacteremia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01898208
• Other study ID #: 11-006920
• Secondary ID: UM1AI104681KL2TR
• Status: Completed
• Phase: N/A
• First received: July 8, 2013
• Last updated: February 17, 2016
• Start date: August 2013
• Est. completion date: August 2014

Study information

• Verified date: February 2016
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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)?

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 information / eligibility

• Status: Completed
• Enrollment: 743
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 99 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Bacteremia
• Bloodstream Infection
• Disease Susceptibility
• Fungemia

Intervention

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.

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.
• 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.

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Mayo Clinic	National Center for Advancing Translational Science (NCATS), National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Oc — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Length of Intensive Care Unit Stay		within 14 days of positive blood culture until ICU discharge	No
Other	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.	Approximately 30 days after positive blood culture	No
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.	Approximately 4 days after enrollment	No
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.	Approximately 14 days after positive blood culture	No
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.	Positive Gram stain, 96 hours after enrollment	No
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.	Within 14 days after positive blood culture	No
Secondary	Time to Pathogen Identification		Approximately 14 days after positive blood culture	No
Secondary	Number of Subjects Who Had Negative Blood Cultures Within 3 Days After Enrollment		3 Days after enrollment	No
Secondary	Length of Entire Hospitalization (Days)		Participants were followed for the duration of hospital stay, approximately 15 days	No
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.	30 days after positive blood culture	No
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.	Approximately 14 days after positive blood culture	Yes
Secondary	Percentage of Subjects With Infectious Disease Consultation Within 72 Hours of Enrollment		Approximately within 72 hours of positive blood culture	No
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.	Approximately 7 days after positive blood culture and for duration of entire hospitalization	No