Rapid Identification and Phenotypic Susceptibility Testing for Gram-Negative Bacteremia

Study Overview
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Brief Summary
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RAPIDS-GN is a multi-center, prospective, randomized, controlled trial to evaluate the following strategies for patients with confirmed gram-negative bacillus bacteremia (GNB): Standard culture and antimicrobial susceptibility testing (AST); or Rapid identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX)

Detailed Description
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RAPIDS-GN is a multi-center, prospective, randomized, controlled trial to evaluate the following strategies for patients with confirmed gram-negative bacillus bacteremia (GNB): Standard culture and antimicrobial susceptibility testing (AST); or Rapid identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX) Patient specimens with positive blood culture with Gram stain showing GNB identified during local laboratory business hours will be enrolled by the Microbiology Laboratory Technologist if they do not meet any exclusion criteria. Subject specimens will be randomized 1:1 to standard culture and AST or Rapid identification and AST using the FDA approved Accelerate Pheno TM System. Both groups will receive standard antimicrobial stewardship (AS). The primary service, including the prescribing provider, will be unaware of group assignment at the time of randomization, so initial antibiotic choice will not be affected by group assignment. Once rapid results become available and/or AS interventions are made, treating providers may become aware of group assignment. The goal of this study is to determine the impact of rapid bacterial identification and phenotypic antimicrobial susceptibility testing (AST) on antimicrobial usage and clinical outcomes.

Official Title
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Rapid Identification and Phenotypic Susceptibility Testing for Gram-Negative Bacteremia (RAPIDS-GN)

Conditions
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Gram-negative Bacteremia

Intervention / Treatment
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* Device: Accelerate PhenoTest™ BC Kit
* Device: Standard Culture and AST


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive blood culture with Gram stain showing GNB identified during local laboratory business hours. Exclusion Criteria: Identification of GNB outside of local laboratory business hours (e.g. whenever laboratories are staffed to perform both rapid testing and routine testing) Positive blood culture for GNB at the same institution within prior 7 days (if known at the time of randomization). Deceased at the time of randomization. GNB plus gram-positive organism, gram-negative cocci, and/or yeast detected on Gram stain Previous enrollment in this study No Minnesota research authorization (Rochester site only)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard blood culture and AST<br>Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship. | Device: Standard Culture and AST<br>* Standard culture and antimicrobial susceptibility testing (AST)<br>|
| Active Comparator: Rapid organism identification and AST<br>Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing. | Device: Accelerate PhenoTest™ BC Kit<br>* Rapid identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hours to First Antibiotic Modification | Mean hours until first modification of antibiotic therapy within 72 hours post randomization | 72 hours after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects Who Experienced Mortality Within 30 Days of Randomization | Subjects who experienced mortality within 30 days of randomization | Within 30 days of randomization | 
| Length of Stay in the Hospital | Length of stay in the hospital after randomization, up to 30 days, for patients alive at 30 days. Length of stay will be date of discharge minus date of randomization. | Within 30 days of randomization | 
| ICU Status Through 72 Hours Post-randomization | ICU status through 72 hours post-randomization | Within 72 hours of randomization | 
| Time to First Antibiotic Escalation | Mean hours to first antibiotic escalation within 72 hours from randomization, where escalation is defined as changing to a broader spectrum antibiotic, addition of one or more antibiotics, or conversion of oral to intravenous route. | Within 72 hours of randomization | 
| Time to First Gram-negative Antibiotic Escalation | Mean hours to first gram-negative antibiotic escalation within 72 hours from randomization, where escalation is defined as changing to a broader spectrum antibiotic, addition of one or more antibiotics, or conversion of oral to intravenous route. | Within 72 hours of randomization | 
| Time to First Gram-positive Antibiotic Escalation | Mean hours to first gram-positive antibiotic escalation within 72 hours from randomization, where escalation is defined as changing to a broader spectrum antibiotic, addition of one or more antibiotics, or conversion of oral to intravenous route. | Within 72 hours of randomization | 
| Time to First Antibiotic De-escalation | Mean hours to first antibiotic de-escalation within 72 hours from randomization, where de-escalation is defined as changing to a narrower spectrum antibiotic, cessation of one or more antibiotics, or changing from an intravenous to oral route of appropriate drug. | Within 72 hours of randomization | 
| Time to First Gram-negative Antibiotic De-escalation | Mean hours to first gram-negative antibiotic de-escalation within 72 hours from randomization, where de-escalation is defined as changing to a narrower spectrum antibiotic, cessation of one or more antibiotics, or changing from an intravenous to oral route of appropriate drug. | Within 72 hours of randomization | 
| Time to First Gram-positive Antibiotic De-escalation | Mean hours to first gram-positive antibiotic de-escalation within 72 hours from randomization, where de-escalation is defined as changing to a narrower spectrum antibiotic, cessation of one or more antibiotics, or changing from an intravenous to oral route of appropriate drug. | Within 72 hours of randomization | 
| Number of Hospital-onset Clostridium Difficile Infections | Acquisition of hospital-onset Clostridium difficile within 30 days, as defined by the National Healthcare Safety Network (NHSN), normalized to 10,000 patient-days. | Within 30 days of randomization | 
| Number of New Hospital-acquired Infections (HAIs) and/or Multidrug Resistant Organisms (MDROs), Normalized to 10,000 Patient-days. | Acquisition of new hospital-acquired infections (HAIs) and/or multidrug resistant organisms (MDROs) within 30 days during index hospitalization identified on routine clinical or surveillance samples. Cultures that will be tracked include the following, from any specimen source, unless otherwise indicated: Methicillin-resistant Staphylococcus aureus Vancomycin-resistant Enterococcus 3rd generation cephalosporin non-susceptible Enterobacteriaceae Carbapenem-resistant Enterobacteriaceae, as defined by the Centers for Disease Control and Prevention (CDC): resistant to imipenem, meropenem, doripenem, or ertapenem OR documentation that the isolate possesses a carbapenemase Multidrug-resistant Pseudomonas aeruginosa (resistant to aminoglycosides, cephalosporins, fluoroquinolones, and carbapenems) Carbapenem-resistant Acinetobacter Candida species (isolated from blood cultures only) | Within 30 days of randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gram-negative Bacteremia, ICU, Critically ill, Intensive Care Unit, Rapid identification, Rapid susceptibility, Accelerate PhenoTest™ BC Kit, Accelerate Pheno™ System (AXDX), Antimicrobial stewardship, Antimicrobial use