Gram-negative Bacteremia
Conditions
Keywords
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
Brief summary
RAPIDS-GN is a multi-center, prospective, randomized, controlled trial to evaluate the following strategies for patients with confirmed gram-negative bacillus bacteremia (GNB): 1. Standard culture and antimicrobial susceptibility testing (AST); or 2. Rapid identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX)
Detailed description
RAPIDS-GN is a multi-center, prospective, randomized, controlled trial to evaluate the following strategies for patients with confirmed gram-negative bacillus bacteremia (GNB): 1. Standard culture and antimicrobial susceptibility testing (AST); or 2. 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.
Interventions
Rapid identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX)
DEVICEStandard Culture and AST
Standard culture and antimicrobial susceptibility testing (AST)
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Vanderbilt University
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Caregiver)
Masking description
Primary service/provider: 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.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hours to First Antibiotic Modification | 72 hours after randomization | Mean hours until first modification of antibiotic therapy within 72 hours post randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay in the Hospital | Within 30 days of randomization | 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. |
| ICU Status Through 72 Hours Post-randomization | Within 72 hours of randomization | ICU status through 72 hours post-randomization |
| Time to First Antibiotic Escalation | Within 72 hours of randomization | 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. |
| Time to First Gram-negative Antibiotic Escalation | Within 72 hours of randomization | 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. |
| Time to First Gram-positive Antibiotic Escalation | Within 72 hours of randomization | 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. |
| Subjects Who Experienced Mortality Within 30 Days of Randomization | Within 30 days of randomization | Subjects who experienced mortality within 30 days of randomization |
| Time to First Gram-negative Antibiotic De-escalation | Within 72 hours of randomization | 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. |
| Time to First Gram-positive Antibiotic De-escalation | Within 72 hours of randomization | 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. |
| Number of Hospital-onset Clostridium Difficile Infections | Within 30 days of randomization | Acquisition of hospital-onset Clostridium difficile within 30 days, as defined by the National Healthcare Safety Network (NHSN), normalized to 10,000 patient-days. |
| Number of New Hospital-acquired Infections (HAIs) and/or Multidrug Resistant Organisms (MDROs), Normalized to 10,000 Patient-days. | Within 30 days of randomization | 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) |
| Time to First Antibiotic De-escalation | Within 72 hours of randomization | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Blood Culture and AST Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship. | 226 |
| Rapid Organism Identification and AST 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. | 222 |
| Total | 448 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Comfort care | 8 | 5 |
| Overall Study | Comfort care and mixed culture | 0 | 1 |
| Overall Study | Comfort care and positive blood culture | 1 | 0 |
| Overall Study | Inaccessible hospital records | 2 | 5 |
| Overall Study | Mixed culture | 2 | 2 |
| Overall Study | No gram-negative bacilli (GNB) | 0 | 2 |
| Overall Study | Prior positive blood culture | 8 | 13 |
| Overall Study | Randomized during laboratory off hours | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Standard Blood Culture and AST | Rapid Organism Identification and AST |
|---|---|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 19.4 | 65.8 years STANDARD_DEVIATION 18.3 | 62.2 years STANDARD_DEVIATION 20.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 13 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 393 Participants | 202 Participants | 191 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 26 Participants | 11 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 10 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants | 9 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 47 Participants | 21 Participants | 26 Participants |
| Race (NIH/OMB) White | 359 Participants | 183 Participants | 176 Participants |
| Region of Enrollment United States | 448 Participants | 226 Participants | 222 Participants |
| Sex/Gender, Customized Female | 195 Participants | 95 Participants | 100 Participants |
| Sex/Gender, Customized Male | 252 Participants | 130 Participants | 122 Participants |
| Sex/Gender, Customized Unknown | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 18 / 226 | 25 / 222 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Hours to First Antibiotic Modification
Mean hours until first modification of antibiotic therapy within 72 hours post randomization
Time frame: 72 hours after randomization
Population: Subjects who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Blood Culture and AST | Hours to First Antibiotic Modification | 24.7 hours | Standard Deviation 24.6 |
| Rapid Organism Identification and AST | Hours to First Antibiotic Modification | 19.0 hours | Standard Deviation 22.9 |
p-value: 0.01395% CI: [1.2, 10]t-test, 2 sided
Secondary
ICU Status Through 72 Hours Post-randomization
ICU status through 72 hours post-randomization
Time frame: Within 72 hours of randomization
Population: Subjects who completed the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Blood Culture and AST | ICU Status Through 72 Hours Post-randomization | In ICU < 72 hours after randomization | 33 Participants |
| Standard Blood Culture and AST | ICU Status Through 72 Hours Post-randomization | In ICU for >= 72 hours after randomization | 34 Participants |
| Standard Blood Culture and AST | ICU Status Through 72 Hours Post-randomization | Not in ICU | 159 Participants |
| Rapid Organism Identification and AST | ICU Status Through 72 Hours Post-randomization | In ICU < 72 hours after randomization | 55 Participants |
| Rapid Organism Identification and AST | ICU Status Through 72 Hours Post-randomization | In ICU for >= 72 hours after randomization | 37 Participants |
| Rapid Organism Identification and AST | ICU Status Through 72 Hours Post-randomization | Not in ICU | 130 Participants |
p-value: 0.014Fisher Exact
Secondary
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.
Time frame: Within 30 days of randomization
Population: Subjects who were alive at 30 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Blood Culture and AST | Length of Stay in the Hospital | 8.2 days | Standard Deviation 8.7 |
| Rapid Organism Identification and AST | Length of Stay in the Hospital | 9.8 days | Standard Deviation 9.8 |
p-value: 0.093t-test, 2 sided
Secondary
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.
Time frame: Within 30 days of randomization
Population: Subjects who completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Blood Culture and AST | Number of Hospital-onset Clostridium Difficile Infections | 26.8 Infections per 10,000 patient-days |
| Rapid Organism Identification and AST | Number of Hospital-onset Clostridium Difficile Infections | 27.5 Infections per 10,000 patient-days |
Secondary
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)
Time frame: Within 30 days of randomization
Population: Subjects who completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Blood Culture and AST | Number of New Hospital-acquired Infections (HAIs) and/or Multidrug Resistant Organisms (MDROs), Normalized to 10,000 Patient-days. | 123.3 Infections per 10,000 patient-days |
| Rapid Organism Identification and AST | Number of New Hospital-acquired Infections (HAIs) and/or Multidrug Resistant Organisms (MDROs), Normalized to 10,000 Patient-days. | 105.5 Infections per 10,000 patient-days |
Secondary
Subjects Who Experienced Mortality Within 30 Days of Randomization
Subjects who experienced mortality within 30 days of randomization
Time frame: Within 30 days of randomization
Population: Subjects who completed the study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Blood Culture and AST | Subjects Who Experienced Mortality Within 30 Days of Randomization | Dead within 30 days | 18 Participants |
| Standard Blood Culture and AST | Subjects Who Experienced Mortality Within 30 Days of Randomization | Not dead within 30 days | 206 Participants |
| Standard Blood Culture and AST | Subjects Who Experienced Mortality Within 30 Days of Randomization | Unknown | 2 Participants |
| Rapid Organism Identification and AST | Subjects Who Experienced Mortality Within 30 Days of Randomization | Dead within 30 days | 25 Participants |
| Rapid Organism Identification and AST | Subjects Who Experienced Mortality Within 30 Days of Randomization | Not dead within 30 days | 197 Participants |
| Rapid Organism Identification and AST | Subjects Who Experienced Mortality Within 30 Days of Randomization | Unknown | 0 Participants |
p-value: 0.265Fisher Exact
Secondary
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.
Time frame: Within 72 hours of randomization
Population: Subjects who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Blood Culture and AST | Time to First Antibiotic De-escalation | 44.2 hours | Standard Deviation 26.2 |
| Rapid Organism Identification and AST | Time to First Antibiotic De-escalation | 39.6 hours | Standard Deviation 28 |
p-value: 0.07495% CI: [-0.4, 9.6]t-test, 2 sided
Secondary
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.
Time frame: Within 72 hours of randomization
Population: Subjects who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Blood Culture and AST | Time to First Antibiotic Escalation | 52.7 hours | Standard Deviation 28.8 |
| Rapid Organism Identification and AST | Time to First Antibiotic Escalation | 45.2 hours | Standard Deviation 31.4 |
p-value: 0.00995% CI: [1.9, 13.1]t-test, 2 sided
Secondary
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.
Time frame: Within 72 hours of randomization
Population: Subjects who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Blood Culture and AST | Time to First Gram-negative Antibiotic De-escalation | 55.8 hours | Standard Deviation 23.5 |
| Rapid Organism Identification and AST | Time to First Gram-negative Antibiotic De-escalation | 49.3 hours | Standard Deviation 27.8 |
p-value: 0.00895% CI: [1.7, 11.2]t-test, 2 sided
Secondary
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.
Time frame: Within 72 hours of randomization
Population: Subjects who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Blood Culture and AST | Time to First Gram-negative Antibiotic Escalation | 53.9 hours | Standard Deviation 28.4 |
| Rapid Organism Identification and AST | Time to First Gram-negative Antibiotic Escalation | 47.5 hours | Standard Deviation 31.2 |
p-value: 0.02295% CI: [0.9, 12]t-test, 2 sided
Secondary
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.
Time frame: Within 72 hours of randomization
Population: Subjects who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Blood Culture and AST | Time to First Gram-positive Antibiotic De-escalation | 60.4 hours | Standard Deviation 22.6 |
| Rapid Organism Identification and AST | Time to First Gram-positive Antibiotic De-escalation | 62.2 hours | Standard Deviation 21.3 |
p-value: 0.3795% CI: [-5.9, 2.2]t-test, 2 sided
Secondary
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.
Time frame: Within 72 hours of randomization
Population: Subjects who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Blood Culture and AST | Time to First Gram-positive Antibiotic Escalation | 70.5 hours | Standard Deviation 9.5 |
| Rapid Organism Identification and AST | Time to First Gram-positive Antibiotic Escalation | 69.7 hours | Standard Deviation 11.3 |
p-value: 0.4695% CI: [-1.2, 2.7]t-test, 2 sided