Clinical trial NCT02743585: Impact of Rapid Pathogen Identification From Blood Cultures (RABbIT)
Official title: Impact of Rapid Pathogen Identification From Blood Cultures (RABbIT - Rapid Blood Culture Intervention Trial)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Bacteremia
Sepsis
Fungemia
Blood Stream Infection
Lead sponsor: Tan Tock Seng Hospital
Sponsor class: OTHER
Collaborators: name: Mayo Clinic
First posted: 2016-04-19
Enrollment: 832
Sex: ALL
Minimum age (years): 21
Maximum age (years): 103
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Septic shock carries high mortality, which may be exacerbated by inappropriate initial therapy. Inappropriate therapy may result from unanticipated antimicrobial resistance. Conversely, positive blood cultures may result from contamination, leading to unnecessary therapy and procedures and possibly prolonged hospitalization. Clinicians may also resort to broad spectrum antimicrobials and be hesitant to de-escalate while awaiting susceptibility results.

The investigators hypothesize that rapid identification of pathogens and antimicrobial resistance will ameliorate the above problems and improve time to optimal therapy, avoid unnecessary therapy and ultimately improve patient outcomes. While there are a number of in-vitro and uncontrolled clinical studies, there is a paucity of well-designed clinical trials objectively examining the real-world clinical and health-economic impact of such technology. To date only one randomised trial has been performed in the US (ClinicalTrials.gov NCT01898208), at a setting with low endemic rates of antimicrobial resistance. This is a companion study to NCT01898208. The investigators aim to study the clinical impact and cost-effectiveness of a strategy for rapid pathogen and resistance detection in a setting with a moderate to high levels of antimicrobial resistance.

Detailed description: Hypothesis:

1. Rapid pathogen identification from blood cultures, including early identification of resistance (via specific genetic markers or phenotypic tests), will allow timelier initiation of appropriate antibiotic therapy and improved patient outcomes
2. Rapid organism identification from blood cultures will allow timelier initiation of effective and optimal antibiotic therapy; minimizing the use of unnecessary antibiotics, including combination therapy

Devices to be studied for this proposed study:

1. BCID panel (Biofire Diagnostics Inc., bioMerieux) : The BCID panel is an FDA-approved nucleic acid amplification test (based on nested polymerase chain reaction) which detects Gram positive, Gram negative, the major Candida species and antimicrobial resistance markers (mecA for methicillin resistance, van A/B for vancomycin resistance, blaKPC for Klebsiella pneumoniae carbapenemase (KPC)) directly from positive blood cultures in \< 1 - 1.5 hours
2. Rosco Diagnostica extended-spectrum beta-lactamase (ESBL) and carbapenemase screen kit (Rosco Diagnostica): These kits are CE-marked (Approved in the European Union) rapid chromogenic tests for ESBL/ carbapenemase detection from both blood cultures and cultured bacterial colonies.

Eligibility criteria: Inclusion Criteria:

1. Age \> 21 years and above to 103 years
2. Blood culture flagged positive on automated instrument, with Gram positive, Gram negative bacteria or Yeast on Gram staining (including polymicrobial blood cultures)
3. Ability to provide informed consent or ability to obtain informed consent from legal guardian/representative (verbal and written)

Exclusion Criteria:

1. Patients whose blood cultures turn positive, but have no organism seen on Gram stain.
2. Patients who have been previously enrolled.
3. Patients who withdraw their consent (verbal or written).
4. Patients with any positive blood culture in the preceding 7 days.

Primary outcomes:
measure: Time from positive blood culture result to effective/optimal antibiotics
timeFrame: Approximately 14 days after positive blood culture
Secondary outcomes:
measure: Clinical outcome (Infection related mortality)
timeFrame: 1 year
measure: Clinical outcome (All-cause related mortality)
timeFrame: 1 year
measure: Clinical outcome (Quality of life)
timeFrame: 1 year
measure: Time from positive blood culture result to bacterial identification
timeFrame: Approximately 3 days
measure: Duration of hospitalization (days)
timeFrame: Participants were followed for the duration of hospital stay, approximately 28 days
measure: Duration of bacteremia/fungemia (days)
timeFrame: Patient-dependent variable, estimated up to 7 days
measure: Time to isolation precautions
timeFrame: Estimated up to 5 days
measure: Antibiotic-associated adverse events
timeFrame: Approximately 14 days after positive blood culture
measure: Antimicrobial utilization (hours/days of therapy)
timeFrame: Approximately 4 days after enrollment
measure: Mean Total Hospitalization Costs Per Subject
timeFrame: Approximately 7 days after positive blood culture for up to an estimated 24 weeks
measure: Mean Laboratory Costs Per Subject
timeFrame: Approximately 7 days after positive blood culture for up to an estimated 24 week
measure: Mean Antimicrobials Costs Per Subject
timeFrame: Approximately 7 days after positive blood culture and for duration of entire hospitalization
measure: Cost-effectiveness analysis
timeFrame: Up to 1 year after enrolment and using a 'modeled horizon' based on sepsis-adjusted life expectancies
measure: Time on effective/optimal antibiotics within first 96 hours of positive blood culture
timeFrame: First 96 hours after blood culture turns positive
Other outcomes:
measure: Time to First Appropriate De-escalation or First Appropriate Escalation of Antibiotics
timeFrame: Positive Gram stain, 96 hours after enrollment
measure: Percent of Contaminated Blood Cultures Not Treated or Treated for Less Than 24 Hours
timeFrame: Within 24 hours after positive blood culture
measure: Length of Entire Hospitalization (Days)
timeFrame: Participants are followed for the duration of hospital stay, approximately 15 days
measure: Percentage of Subjects With Infectious Disease Consultation Within 72 Hours of Enrollment
timeFrame: Approximately within 72 hours of positive blood culture
measure: Length of Intensive Care Unit Stay (days)
timeFrame: Within 14 days of positive blood culture until ICU discharge, up to an estimated 24 weeks.
measure: Percentage of Patients Who Acquired Clostridium Difficile Within 30 Days After Enrollment
timeFrame: Approximately 30 days after positive blood culture
measure: Percentage of Patients Who Acquired Multidrug-resistant organisms Within 30 Days After Enrollment
timeFrame: Approximately 30 days after positive blood culture
Locations:
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
Study officials:
affiliation: Tan Tock Seng Hospital
name: Shawn Vasoo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tan Tock Seng Hospital
name: Partha P De, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National University of Singapore/Tan Tock Seng Hospital
name: Christine B Teng, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ong SWX, Hon PY, Wee SSH, Chia JWZ, Mendis S, Izharuddin E, Lin RJ, Chia PY, Sim RCS, Chen MI, Chow A, Yoong J, Lye DC, Teng CB, Tambyah PA, Banerjee R, Patel R, De PP, Vasoo S. Accuracy of a Rapid Multiplex Polymerase Chain Reaction Plus a Chromogenic Phenotypic Test Algorithm for Detection of Extended-Spectrum beta-Lactamase and Carbapenemase-Producing Gram-Negative Bacilli in Positive Blood Culture Bottles. Clin Infect Dis. 2022 May 30;74(10):1850-1854. doi: 10.1093/cid/ciab848.