UCalgary-led team develops rapid diagnostic tool for fighting bloodstream infections

A team led by Faculty of Science biochemist Dr. Ian Lewis, PhD, has developed a new technology to rapidly detect potentially life-threatening bloodstream infections. Using current technologies, it typically takes two to four days to identify infection-causing bacteria and determine which antibiotics will work. The rapid test can provide a result in under 20 hours.

“When you have a bloodstream infection, the length of time that elapses between your arrival at a hospital and when you are administered the correct antibiotic is directly related to your chances of survival,” says project lead Lewis, associate professor in the Department of Biological Sciences and Alberta Innovates Translational Health Chair.

This new technology was developed in partnership between the University of Calgary, Alberta Precision Laboratories (APL), and Thermo Fisher Scientific. The first description of the technology was recently published in the journal Nature Communications.

Some 200,000 Canadians are diagnosed annually with bloodstream infections, caused by several types of pathogenic (disease-causing) bacteria including Staphylococcus aureus and Escherichia coli. About 8,000 of these patients die each year from sepsis and other complications.

The challenge with the current diagnostic method is that a lot of  time is spent waiting for the ‘bugs’ to grow in culture in the laboratory until there are sufficient numbers of bacteria in the culture tube to be detected. The method we’ve developed is over 2.5 times faster.
- Ian Lewis

The group is refining this system for clinical testing in hopes it could become a new standard of testing.

“The faster we can get patients the right antibiotic, the better their outcome,” says project end-user lead Dr. Hallgrimur Benediktsson, MD, former South Zone medical director at APL, and professor in the Department of Pathology & Laboratory Medicine at UCalgary's Cumming School of Medicine.

Some microbes have developed resistance to certain antibiotics and can cause fatal infections if not treated with very specific drug cocktails. A faster diagnostic approach means that physicians will be able to provide the optimum antibiotic regimen earlier to patients with these dangerous infections.

“It is important to use the right combination of antibiotic drugs to treat these infections in order to decrease the likelihood of the underlying bacteria becoming resistant,” says Benediktsson. “Knowing which antibiotic is best for a given infection is essential for the well-being of patients, and for minimizing the spread of resistant microbes.”

Exploiting bacterial metabolism

The team’s new system uses a technology called ‘boundary flux’ analysis. It relies on a high-resolution mass spectrometer — like the ones in the Lewis lab — to identify and characterize the metabolites or molecules that bacteria consume as nutrients and secrete as waste.

These metabolites can be 500,000 times more abundant in a blood sample than the bacteria producing them, so they can be detected much faster, Lewis notes. In addition, each species of bacterium can be identified by the characteristic metabolites it eats and secretes.

“As it turns out, metabolites are fabulous diagnostic indicators for particular species of pathogen. They are also very sensitive reporters of antibiotic susceptibility,” Lewis says.

Thousands of metabolites are produced by bacteria, but the Lewis lab has been able to prioritize 35 of these as diagnostic ‘markers’. “Using those 35 markers, we can very rapidly differentiate between all the bugs that are responsible for over 85 per cent of bloodstream infections, and by measuring their rates of production and consumption, we can tell if a bug is sensitive to a given antibiotic.”

“Changes to metabolite flux can be identified in a minutes-long incubation,” says study lead author Dr. Thomas Rydzak, PhD, Eyes High Scholar and research associate in the Faculty of Science. “This means that we no longer have to grow bugs for hours to days to see if they are affected by a particular drug.”

Collaboration spurs 'translational research'

Both Lewis and Benediktsson emphasize the central role collaboration has played in the success of the program. Early investments from Alberta Innovates and the UCalgary Vice-President (Research) Biomedical Engineering strategy match funding competition in 2016 provided the foundation for this program, which was accelerated thanks to a $6 million Genomics Application Partnership Program (GAPP) award from Genome Canada and via a research collaboration with Thermo Fisher Scientific.  

Currently, the team is working to translate this transformative technology into a real-world device that can be implemented globally. This large-scale vision has been made possible through a collaboration with Thermo Fisher Scientific, an industry leader in the manufacturing of diagnostic equipment.

“These discoveries are being translated for clinical use,” says Lewis. “Having a technology giant like Fisher Scientific on board means that technical aspects of our device match the real-world constraints of medical devices. Our Thermo Fisher partnership is a key component to achieving our vision of saving lives through rapid diagnostics.”

In addition, access to APL’s clinical facilities have been instrumental in preparing the device for use in hospitals. “By collaborating with one of the largest consolidated diagnostic labs in North America, our team has direct access to patient blood samples and clinical instrumentation to translate and refine our tools for clinical use,” says Lewis.

APL has built a repository of bloodstream infection microbes collected directly from patients in Alberta. With more than 30,000 of these anonymous samples available for ethically approved research purposes in APL’s facilities, the team can easily tap these clinical resources to rapidly test and improve all aspects of their device — from the underlying analytics, to its engineering, to its clinical implementation.

These sorts of resources allow us to do research here in Alberta that would be impossible elsewhere.

Team members say the project’s “translational research” approach wouldn’t be possible without all parties collaborating from the onset. “Without the unique physical infrastructure, resource sharing agreements, samples, and expert partners involved in this project, we would not be able to successfully move this precision diagnostic device into a commercialization stream,” says Lewis.

“We want our device implemented in hospitals across the globe as soon as possible, so clinicians have a usable, practical tool to save patients’ lives.”

Market-ready tool poised for global impact

Once final validation is complete, the team will focus on integrating their metabolomics-based platform with existing diagnostic lab infrastructure and will accelerate the commercial rollout of the device.

“This is a practical tool that effectively addresses a solvable problem in clinical microbiology,” says Lewis.

As infections from antibiotic-resistant bacteria become more common, the need for new approaches to for diagnosing infections could never be more pressing.  The work by Lewis and Benediktsson’s team is an important first step in saving the millions of lives that hang in the balance.