Calgary team leads international effort to reduce death and disability from infections

The University of Calgary and Calgary Laboratory Services (CLS) are leading an $11-million program to develop a new strategy to combat infections.

Precision Infection Management (PIM) will allow doctors to rapidly identify serious infections and stop them before they develop into life-threatening conditions, says Ian Lewis, an Alberta Innovates Translational Health Chair-Metabolomics at the university’s Faculty of Science.

PIM will also minimize side-effects from antibiotics by tailoring therapy according to each patient’s needs, he says, adding PIM may also play an important role in fighting the spread of antibiotic resistant bacteria. If left unchecked, the worldwide spread of resistance among disease-causing microbes could cause life expectancy in Canada to plunge by up to 20 years as of 2050, he says.

'Immense undertaking' requires massive computer database

“Although PIM is not going to solve the global crisis in antibiotic resistance, it will extend the service life of antibiotics and prevent people from getting unnecessary complications associated with the current infection management approach,” says Lewis, who is also an assistant professor of biological sciences and director of the Calgary Metabolic Research facility in the International Microbiome Centre.

A grant totalling $11 million was announced Jan. 23 to help drive the development of PIM. These funds include contributions from Genome Canada with support from the Government of Alberta — including Alberta Health Services (AHS) and CLS — as well as WestGrid and the Broad Institute, a world leader in genomics, or the study of the DNA and genes of organisms.

Additional partners in the PIM team include Compute Canada, the University of Wisconsin and the Harvard T. H. Chan School of Public Health.

“Together, WestGrid and Compute Canada bring extensive experience in supporting large-scale science projects, building tools for communities of researchers, and enabling massive computing and data management efforts, so we are very excited to be involved in this partnership,” says Lindsay Sill, WestGrid’s chief executive officer. “A collaboration of this scope and scale depends not only on powerful computing infrastructure but also specialized technical expertise, which is why WestGrid is also contributing key members of our regional team — from database architects to senior programmers to data security experts — to meet the needs of this leading-edge project in genomics and precision health.”

Describing the program as an “immense undertaking,” Lewis says PIM will require a massive computer database — ResistanceDB — linking microbial traits to patient risk factors. “We are analyzing over 50,000 bacterial isolates gathered by CLS and linking their detailed biochemical data to medical records,” he says. “Nothing like it has ever been done on that scale.”

Risk assessments guide doctors

ResistanceDB, which will be hosted by Compute Canada, will combine biochemical information on both pathogens and patients from a wide variety of scientific disciplines, says Lewis.

“This sophisticated data will be used to map the microbial predictors of patient outcome,” he says. “ResistanceDB tracks the most dangerous traits in bugs, uses that information to predict patient outcomes, and returns risk assessments to doctors across Canada to help guide therapy.”

PIM will integrate information from ResistanceDB with clinical information to help clinicians tailor the precise treatment of patients with infections, says Dr. Deirdre Church, a professor in the departments of Pathology & Laboratory Medicine and Medicine  at the University of Calgary’s Cumming School of Medicine (CSM), who is also the clinical section chief for microbiology at CLS.

These risk assessments will be deployed using the Spectrum smartphone app, which was created by a multi-disciplinary team from UCalgary and AHS, she says.

“Right now, all antibiotic therapy is empiric,” says Church. “Infection is generally treated because we don’t get a lot of information about the microorganism from the laboratory system because of a shortfall in technology.”

'Superbugs' boost risk

Overuse of antibiotics in everything from human patients to agriculture has led to the widespread presence of the drugs in the environment, forcing microbes to evolve resistance. The rise of so-called superbugs in hospitals could eventually make procedures ranging from organ transplants and hip replacements to chemotherapy too risky.

Under-treatment is also a problem, says Church, giving the hypothetical example of a patient who first seems to have a localized infection. “But the bug is actually quite severe,” she says. “If we had known three days ago that this strain was actually more serious or nasty, we could have reacted more aggressively up front.”

Not all pathogens are created equal, says Church, who is also a member of the Snyder Institute for Chronic Diseases at CSM. “This strain in one patient may have a very serious outcome, whereas in another patient, it may not be that harmful.”

It currently can take several days to grow microbes in the lab from patient samples, and for test results to become available to readjust therapy, she says. “If you get an inappropriate antibiotic that is not effective against the bloodstream infection that you have, every hour counts in terms of survival and outcome.”

PIM will speed up diagnosis, treatment

PIM, which will be made possible via ResistanceDB and the smartphone app, will speed up the diagnosis and treatment of dangerous infections and will reduce unnecessary antibiotic therapy. Recent technological advances in gene sequencing, protein analysis, and metabolic characterization are critical for PIM.

This concept would not have been possible even a couple of years ago, says Lewis. “We are really at the cutting edge of what is possible."

"This project is a great example of what we are trying to do in the Faculty of Science, which is to bring innovation and discovery to real-world problems that matter to society,” says Associate Dean Research and Graduate Education Eric Donovan. “This is a major step forward for our faculty under our Grand Challenge entitled Personalized Health at the Molecular Level.”

As part of its strategic direction for 2017-2022, the Faculty of Science is directing its research efforts toward four Grand Challenges. The Grand Challenges harness our current strengths, look to future opportunities, and are a framework for doing research that impacts our community and the world. Research under the Grand Challenge Personalized Health at the Molecular Level includes drug synthesis, delivery, and diagnostics, minimizing antibiotic resistance in bacteria, and understanding the role molecules have in our health.

The University of Calgary’s multidisciplinary Engineering Solutions for Health: Biomedical Engineering research strategy drives solutions to our most pressing health challenges in disease and injury prevention, diagnosis and treatments. Our biomedical engineering researchers make a significant impact in our communities by extending lives, improving quality of life, promoting independence, and continuously improving the health system.