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A race against the clock: how a new metabolomics assay for bloodstream infections could save lives

A difference in hours can be lifesaving when it comes to diagnosis and treatment of bloodstream infections (BSI). Currently, it takes approximately two to four days from when a BSI is suspected to time of treatment with the correct antibiotics. 
There are over 500,000 bloodstream infections diagnosed per year in North America with over 80,000 cases resulting in death. A patient’s odds of survival depend on the length of time taken from onset of symptoms to diagnosis to treatment with the appropriate antibiotics. Most diagnostic laboratories require one to five days to determine the pathogen, followed by anti-microbial susceptibility testing, where 20-30% of patients are prescribed the wrong antimicrobial treatment at first. Development of a more precise and efficient way to treat BSI is vital.

Dr. Ian Lewis, Alberta Innovates Translational Health Chair and Associate Professor at the University of Calgary, and Dr. Hallgrimur Benediktsson MD, interim South Zone Medical Director at Alberta Precision Laboratories and Professor at the University of Calgary, co-led a Genome Alberta/Genome Canada Genomic Application Partnership Program (GAPP) project to address the development of new technology for rapid diagnosis and treatment of BSI.
“If put into practice across North America and Europe, this technology could save as many as 50,000 lives a year through faster diagnostics. We are grateful to Genome Canada, Genome Alberta, Thermo Fisher, and Alberta Public labs for making this concept a reality" – Dr. Ian Lewis, University of Calgary.
Through the GAPP project teams at the University of Calgary, Alberta Precision Laboratories, and Thermo Fisher Scientific have developed new technology that can provide results for BSI in under 20 hours. This is 2.5 times faster than the current technology used in health care. Their findings were published in Nature Communications.

“Rapid diagnostic tools are urgently needed for detecting bloodstream infections. We are thrilled that Thermo Fisher Scientific’s mass spectrometry platforms are playing a key role in redefining the state-of-the-art technology for infectious disease detection and characterization.” - Brad Hart Sr Director, Analytical Vertical and LSMS Marketing, Analytical Instruments Group at Thermo Fisher Scientific.

The team developed a rapid diagnostic tool called the Metabolic Preference Assay (MPA) that identifies pathogens that cause BSI, as well as determining their susceptibility to antibiotics. MPA uses metabolomics to accelerate diagnostics. Metabolomics is the systematic study of small molecules known as metabolites within a biological system. Metabolites are more abundant than proteins and serve as reporters of microbial physiology, which can be used for highly efficient mass spectrometry experiments.

In current health settings, diagnosis involves a time-consuming set up and amplification of microbial cultures, followed by antimicrobial susceptibility testing - all limited by microbial growth rates. The MPA avoids this limiting step by allowing for sensitive and efficient testing of excreted metabolites from microbial cultures to not only identify the pathogen but understand their antimicrobial susceptibility to drug treatments. The team identified metabolites that can differentiate seven of the most prevalent organisms responsible for BSI and developed the Metabolic Inhibition Assay (MIA) to measure changes in metabolite levels in response to antimicrobials. The high sensitivity and abundance of metabolites allows the MPA/MIA technology to reduce the time it takes from diagnosis to identification of appropriate treatment for BSI.

“Through this partnership microbial isolates collected by a province-wide publicly funded system were made available for large metabolomics research at the University of Calgary that resulted in the development of this rapid diagnostic tool. As a funder and taxpayer, it is satisfying to see the return on this investment” – Dr. Gijs van Rooijen, Chief Scientific Officer at Genome Alberta.

The team is currently testing their new technology in a clinical setting and hopes that once validation is complete, it could become the new standard of testing. This newly developed assay could reduce septic shock mortality and reduce the use of untargeted broad-spectrum antibiotics. By accelerating the time from diagnosis to treatment with the correct antibiotics, this new technology could change treatment of bloodstream infections and save lives.

To read more about this new technology and the teams that led its development see the feature in
UCalgary Today “UCalgary-led team develops rapid diagnostic tool for fighting bloodstream infections”.

A race against the clock: how a new metabolomics assay for bloodstream infections could save lives

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