Actionable Results: Bloodstream Infection Molecular Assay Evaluation

Assessment of the Use and Impact of a Molecular Identification Assay in the Diagnosis and Management of Bloodstream Infections at in Healthcare Settings in Princess Marina Hospital, Botswana

A number of rapid panel-based molecular assays for direct organism identification and resistance characterization in positive blood culture bottles are now commercially available. They have been shown to improve accuracy and decrease the time-to-result, allowing targeted treatment in hospitalized patients with bacteraemia, in high-income countries (HICs). However, these molecular assays are add-on tests performed in addition to conventional testing, increasing the complexity of diagnostic algorithms and costs of patient care. Conventional organism identification includes performing a Gram stain, biochemical identification and phenotypic drug susceptibility testing. The FilmArray Blood Culture Identification (BioFire, USA) is an example of a rapid panel-based molecular assay that combines nesting and multiplexing of PCR (nested multiplex PCR) to detect multiple pathogens simultaneously. There are limited data on how such tests impact patient management, health care costs and how they can better be incorporated into diagnostic algorithms.

The aim of this study is to assess the added value and acceptability of a multiplexed molecular diagnostic assay in the identification of pathogens in patients presenting with bacteremia at hospitals in LMICs, and to assess health care providers' satisfaction with the assay.

Study Overview

• Status: Completed
• Conditions: Bloodstream Infection
• Intervention / Treatment: Diagnostic test: Multiplex molecular diagnostic assay

Detailed Description

The study will address the following questions:

1. What impact can we project if additional diagnostic information were to be provided to clinicians in terms of patient outcomes, costs, and antibiotic use?
2. What are the workflow constraints on returning diagnostic results to clinicians and/or antibiotic stewardship programs? Overall, the aim is to assess the added value and acceptability of a multiplexed molecular diagnostic assay in the identification of pathogens in patients presenting with bacteremia at hospitals in LMICs and to assess health care providers' satisfaction with the assay.

• Study Type: Interventional
• Enrollment (Actual): 312
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Botswana
  • Gaborone, Botswana
    • Princess Marina Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For patients of Princess Marina Hospital: all participants who have a blood culture done as part of routine clinical care that is found to be positive through routine laboratory testing from Monday-Friday 8am-3pm (excluding holidays) will be eligible for inclusion in the study, regardless of age and co-morbidities.
• For the professionals making use of molecular testing: Attending physicians (paediatricians, internists, and physician trainees [residents, medical officers, interns]) caring for adults and children who are enrolled in the study, Microbiologists and microbiology technologists who have experience operating the BioFire FilmArray and/or traditional blood culture incubation systems at the laboratory.

Exclusion Criteria:

• For patients of Princess Marina Hospital: Individuals who have previously participated in the study by having a blood culture positive in the week prior will not be eligible to participate again within the 7-day time frame.
• For professionals making use of molecular testing: Individuals working with patients or laboratory samples at Princess Marina Hospital for less than one month will not be asked to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Molecular dx arm; Positive blood cultures are tested using a molecular ID system in addition to the standard of care (biochemical identification)	Diagnostic test: Multiplex molecular diagnostic assay; To assess the added value and acceptability of a multiplexed molecular diagnostic assay in the identification of pathogens in patients presenting with bacteremia at hospitals in LMICs, and to assess health care providers' satisfaction with the assay.
No Intervention: Standard of care arm; Positive blood cultures are treated as per normal lab protocol (biochemical identification)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from blood collection to definitive treatment initiation (optimal treatment defined as time from blood culture collection to the initiation of a predetermined pathogen-specific antimicrobial therapy)	The judgment as to whether antimicrobial treatment was effective or optimal will be assessed by two members of the study team (infectious disease specialists and/or microbiologists) blinded to treatment group. A third, blinded, party member will be available to adjudicate unresolved disagreements. The Principal Investigators will not be involved in outcome classification.	1year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from blood collection to initiation of effective antimicrobial therapy (initiation of antimicrobials active against the identified causative pathogen)	The aim is to understand the reduction in time it takes clinical staff to act upon the result. Faster treatment is associated with reduced mortality.	1year
Time from blood collection to pathogen identification	The hypothesis is that faster identification will lead to faster action.	1year
Proportion of patients with a confirmed diagnosis of bloodstream infection who are started on optimal antimicrobial therapy in the intervention compared to control arm.	This outcome will inform how the inclusion of a faster diagnosis can support antibiotic stewardship efforts.	1year
Frequency of discrepant results between molecular identification vs standard of care.	Current panels are design for common pathogens in the USA and Europe and given that this is the first evaluation in Africa it will advice on the suitability.	1year
Clinicians' satisfaction with the assay, predominantly in terms of time-to-result and actionable results.	To inform future projects and help guide implementation efforts.	2month
Laboratory professional satisfaction with the assay, predominantly in terms of ease of use and workflow.	To inform future projects and help guide implementation efforts.	2month
In-hospital mortality.	Faster treatment is associated with reduced mortaltity and as a secondary outcome we want to assess the difference between standard of care and diagnostic intervention.	1year
30-day mortality.	Faster treatment is associated with reduced mortaltity and as a secondary outcome we want to assess the difference between standard of care and diagnostic intervention.	1year

Collaborators and Investigators

• Sponsor: Foundation for Innovative New Diagnostics, Switzerland
• Investigators: Principal Investigator: Jeffrey Pernica, MD, FRCPC, McMaster University; Principal Investigator: David Goldfarb, MD, FRCPC, University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2018
• Primary Completion (Actual): March 31, 2020
• Study Completion (Actual): March 31, 2020

Study Registration Dates

• First Submitted: August 17, 2017
• First Submitted That Met QC Criteria: August 17, 2017
• First Posted (Actual): August 21, 2017

Study Record Updates

• Last Update Posted (Actual): March 10, 2021
• Last Update Submitted That Met QC Criteria: March 9, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Infections; Communicable Diseases
• Other Study ID Numbers: 08821/1/1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No