Performance evaluation of InfectID-BSI: A rapid quantitative PCR assay for detecting sepsis-associated organisms directly from whole blood

Lisa A Simms; Corey Davies; Nadeesha Jayasundara; Sumeet Sandhu; Alexander Pintara; Amorette Pretorius; Graeme R Nimmo; Jacqueline Harper; Matthew Hiskens; Karen Smith; Sarah Boxall; Anton Lord; Raffaella Giardino; David Farlow; Diane M Ward; Flavia Huygens

doi:10.1016/j.mimet.2023.106783

Performance evaluation of InfectID-BSI: A rapid quantitative PCR assay for detecting sepsis-associated organisms directly from whole blood

J Microbiol Methods. 2023 Aug:211:106783. doi: 10.1016/j.mimet.2023.106783. Epub 2023 Jul 12.

Authors

Lisa A Simms¹, Corey Davies¹, Nadeesha Jayasundara¹, Sumeet Sandhu², Alexander Pintara¹, Amorette Pretorius¹, Graeme R Nimmo³, Jacqueline Harper⁴, Matthew Hiskens⁵, Karen Smith⁶, Sarah Boxall⁷, Anton Lord⁸, Raffaella Giardino¹, David Farlow⁹, Diane M Ward¹⁰, Flavia Huygens¹¹

Affiliations

¹ Microbio Ltd., Translational Research Institute, Brisbane, Queensland 4102, Australia.
² Microbio Ltd., Translational Research Institute, Brisbane, Queensland 4102, Australia; Queensland Health, Brisbane, Queensland, Australia.
³ Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland 4029, Australia; School of Medicine, Griffith University, Gold Coast, Queensland, Australia.
⁴ Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland 4029, Australia.
⁵ Mackay Institute of Research and Innovation, Mackay Hospital and Health Service, Mackay, Queensland 4740, Australia.
⁶ Mackay Institute of Research and Innovation, Mackay Hospital and Health Service, Mackay, Queensland 4740, Australia; Department of Emergency Medicine, Mackay Hospital and Health Service, Mackay, Queensland 4740, Australia.
⁷ Department of Emergency Medicine, Mackay Hospital and Health Service, Mackay, Queensland 4740, Australia.
⁸ Spectroscopy and Data Consultants, Brisbane, Queensland, Australia.
⁹ Microbio Ltd., Translational Research Institute, Brisbane, Queensland 4102, Australia; Mackay Institute of Research and Innovation, Mackay Hospital and Health Service, Mackay, Queensland 4740, Australia.
¹⁰ Qserve Consultancy B.V - HQ, Arnhems Bussiness Park, Utrechtseweg 310 Bldg B42, 6812 AR Arnhem, The Netherlands.
¹¹ Microbio Ltd., Translational Research Institute, Brisbane, Queensland 4102, Australia. Electronic address: fhuygens@microbio.com.au.

PMID: 37442279
DOI: 10.1016/j.mimet.2023.106783

Abstract

Background: Bloodstream infections (BSIs) (presence of pathogenic organism in blood) that progress to sepsis (life-threatening organ dysfunction caused by the body's dysregulated response to an infection) is a major healthcare issue globally with close to 50 million cases annually and 11 million sepsis-related deaths, representing about 20% of all global deaths. A rapid diagnostic assay with accurate pathogen identification has the potential to improve antibiotic stewardship and clinical outcomes.

Methods: The InfectID-Bloodstream Infection (InfectID-BSI) test is a real-time quantitative PCR assay, which detects 26 of the most prevalent BSI-causing pathogens (bacteria and yeast) directly from blood (without need for pre-culture). InfectID-BSI identifies pathogens using highly discriminatory single nucleotide polymorphisms located in conserved regions of bacterial and fungal genomes. This report details the findings of a patient study which compared InfectID-BSI with conventional blood culture at two public hospitals in Queensland, Australia, using 375 whole blood samples (from multiple anatomical sites, eg. left arm, right arm, etc.) from 203 patients that have been clinically assessed to have signs and symptoms of suspected BSI, sepsis and septic shock.

Findings: InfectID-BSI was a more sensitive method for microorganism detection compared with blood culture (BacT/ALERT, bioMerieux) for positivity rate (102 vs 54 detections), detection of fastidious organisms (Streptococcus pneumoniae and Aerococcus viridans) (25 vs 0), detection of low bioburden infections (measured as genome copies/0.35 mL of blood), time to result (<3 h including DNA extraction for InfectID-BSI vs 16 h-48 h for blood culture), and volume of blood required for testing (0.5 mL vs 40-60 mL). InfectID-BSI is an excellent 'rule out' test for BSI, with a negative predictive value of 99.7%. InfectID-BSI's ability to detect 'difficult to culture' microorganisms re-defines the four most prevalent BSI-associated pathogens as E. coli (28.4%), S. pneumoniae (17.6%), S. aureus (13.7%), and S. epidermidis (13.7%).

Interpretation: InfectID-BSI has the potential to alter the clinical treatment pathway for patients with BSIs that are at risk of progressing to sepsis.

Keywords: Blood culture; Bloodstream infections; Quantitative PCR; Rapid diagnostics; Sepsis; Septic shock; qPCR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bacteria / genetics
Escherichia coli*
Humans
Real-Time Polymerase Chain Reaction / methods
Saccharomyces cerevisiae
Sepsis* / diagnosis
Sepsis* / microbiology
Staphylococcus aureus