Impact of Rapid Pathogen Identification From Blood Cultures (RABbIT)

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.

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.