Frankel Innovation Initiative awards Weil Institute investigators $250,000 to identify sepsis-causing bacteria faster and more accurately than gold-standard methods
The team’s technology will determine the identity and concentration of pathogens within 3 hours, drastically reducing time to diagnosis and treatment.
Contact:
Kate Murphy, Marketing Communications Specialist, Weil Institute
mukately@med.umich.edu
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ANN ARBOR – A research team from the Max Harry Weil Institute for Critical Care Research and Innovation and Michigan Medicine received $250,000 to support work on a new tool that could revolutionize pathogen detection in patients with sepsis. The funding was awarded through the University of Michigan Frankel Innovation Initiative, which supports the research and development of life-saving therapies and innovative new technologies at Michigan Medicine with the goal of improving healthcare and saving lives.
“We urgently need diagnostics that can quickly detect and identify pathogens and help us prescribe the right drug for the right bug in sepsis,” said Dr. J. Scott VanEpps, an Associate Director of the Weil Institute and Assistant Professor of Emergency Medicine. Dr. VanEpps, together with Co-Principal Investigator Dr. Vishwaratn Asthana, resident physician in the Department of Internal Medicine, leads development of the newly Frankel Award-funded “Rapid Response” (R²) system, a bacterial detection assay poised to transform sepsis care by drastically reducing time to diagnosis and initiation of targeted treatments.
Sepsis occurs when the body’s immune response to an infection causes widespread, uncontrolled inflammation. To manage this deadly condition, clinicians must promptly detect and treat the bacteria responsible for the initial infection. However, current methods of identifying these pathogens are time-intensive and limited in what they can detect. This can lead to delays in diagnosis and, subsequently, worsening patient outcomes.
Unlike current gold-standard pathogen detection methods that can take up to 48 hours for analysis and rely on culturing (reproducing bacteria in a lab environment), the R² assay uses an approach similar to polymerase chain reaction (PCR) tests by analyzing sets of DNA and RNA features—called “primers”—that are unique across different species of bacteria. Using these primers, the system can determine pathogen identity and concentration within 3 hours and, unlike PCR tests, isn’t limited to a small subset of sepsis pathogens.
“These were the issues that inspired me to design the R² system,” said Dr. Asthana. “Culturing has become so deeply ingrained in clinical practice, but it has many deficits. Sequencing is hailed as the diagnostic of the future, but it currently takes too long, is too expensive, and struggles with complex microbial samples.”
Along with expediting pathogen detection and identification, the R² system’s rapid and accurate turnaround will also help mitigate the need for “broad-spectrum” antibiotics. In cases where the physician suspects sepsis but has no way of immediately knowing the pathogen causing it, they prescribe antibiotics that target a wide range of bacteria to prevent the patient’s condition from worsening. This can lead to complications such as under- or overtreatment, disruption of the body’s natural bacterial microbiome, and contribute to the development of antibiotic-resistant “superbugs”.
"Culturing has become so deeply ingrained in clinical practice, but it has many deficits. Sequencing is hailed as the diagnostic of the future, but it currently takes too long, is too expensive, and struggles with complex microbial samples."
Vishwaratn Asthana, MD, PhD
Resident Physician, Department of Internal Medicine
“Getting the right antibiotic to the patient in a timely fashion is critical,” said co-investigator Dr. Robert Dickson, a Deputy Director at the Weil Institute and Associate Professor of Pulmonary & Critical Care Medicine. “We know that we can hurt patients both by undertreating and overtreating infections, and our current diagnostic tools just aren't up to the task. If R² can cut the time it takes to identify pathogens from days to hours or even minutes, it could transform our approach to source control and antimicrobial stewardship.”
Previously, the R² team completed proof-of-concept work on their device and developed a set of bacterial DNA primers for 45 common clinical pathogens. Now, with the additional support from the Frankel Innovation Initiative, the team will be able to develop and optimize more sets of primers to improve the R² system’s pathogen coverage. They will also be able to further test the device against current culture-based methods of detecting bacteria in human blood, urine and respiratory tract samples. While the team sees their device initially working in parallel with these methods, they ultimately envision it will replace them entirely.
“By speeding up time to diagnosis and eliminating false negative secondary to culturing, our system has the potential to improve clinical outcomes including morbidity, mortality, hospital length of stay and reduced healthcare costs,” said Dr. VanEpps.
Project Team
J. Scott VanEpps, MD, PhD (Weil Institute, Emergency Medicine); Vishwaratn Asthana, MD, PhD (Weil Institute, Internal Medicine); Robert Dickson, MD (Weil Institute, Internal Medicine, Pulmonary & Critical Care Medicine, Microbiology and Immunology); Pallavi Bugga, PhD (Pyogenix, Inc.); Erika Martinez-Nieves, MS (Bioengineering, Emergency Medicine); Piyush Ranjan, MSc (Internal Medicine)
Disclosures
An invention disclosure for the R² technology has been filed with the UM Office of Innovation Partnerships, and IP has been assigned to UM under an option agreement.
The UM-based start-up company Pyogenix, Inc. was created to facilitate future fundraising and commercialization of the R² technology. Dr. Asthana and Dr. Bugga have equity in Pyogenix.
About the Max Harry Weil Institute for Critical Care Research and Innovation
The team at the Max Harry Weil Institute for Critical Care Research and Innovation (formerly the Michigan Center for Integrative Research in Critical Care) is dedicated to pushing the leading edge of research to develop new technologies and novel therapies for the most critically ill and injured patients. Through a unique formula of innovation, integration and entrepreneurship that was first imagined by Weil, their multi-disciplinary teams of health providers, basic scientists, engineers, data scientists, commercialization coaches, donors and industry partners are taking a boundless approach to re-imagining every aspect of critical care medicine. For more information, visit www.weilinstitute.med.umich.edu.