Weil Institute team develops tool to expedite diagnosis of bloodstream infections
The culture-free platform is as accurate as current culture-based diagnostics but produces results in a matter of hours instead of days.
Contact:
Katelyn Murphy
Marketing Communications Specialist, Weil Institute
mukately@med.umich.edu
ANN ARBOR, MI – When a patient presents with a bloodstream infection (BSI), care teams must quickly identify the species of bacteria responsible for the infection and determine which antibiotic will be most effective. Early administration of a targeted, pathogen-specific treatment is key to a good outcome. However, the current gold standard workflow for diagnosing BSIs can take multiple days due to its reliance on culturing (growing bacteria in a controlled laboratory setting).
"There is a huge discrepancy in how quickly we need to know the species of bacteria that’s causing an infection and what it’s susceptible to, and how long it takes us to get that information. We typically start antibiotics and get culture simultaneously, but it could still be 2-3 days before we get the information we need. Our goal with this platform is to skip all of that and detect the bacteria in the very beginning."
J. Scott VanEpps, MD, PhD
Associate Professor, Emergency Medicine, Macromolecular Science and Engineering
University of Michigan
To address the urgent need for reducing time-to-diagnosis in BSIs, a team of clinicians and engineers from the Max Harry Weil Institute for Critical Care Research and Innovation, Cleveland State University and start-up company Rapidect, Inc. are developing a rapid, ultrasensitive assay that can accurately detect and identify pathogens in blood without the need for bacteria culturing.
“There is a huge discrepancy in how quickly we need to know the species of bacteria that’s causing an infection and what it’s susceptible to, and how long it takes us to get that information,” said Dr. J. Scott VanEpps, an Associate Director of the Weil Institute, Associate Professor of Emergency Medicine and Macromolecular Science and Engineering at U-M, and one of the developers of the “rapid detection-analysis platform” (RDAP). “Because bacteria are so small, and because some infections have such a small amount of them to detect, we have to first grow enough bacteria in culture in order to find them. We typically start antibiotics and get culture simultaneously, but it could still be 2-3 days before we get the information we need. Our goal with this platform is to skip all of that and detect the bacteria in the very beginning.”
RDAP incorporates a technique called field effect enzymatic detection (FEED), in which a series of ultrasensitive electrodes detect changes in electrical charge that occur when enzymes interact with a substrate (in this case, bacteria). FEED is incredibly useful in diagnostics as it allows doctors to observe which enzymes are active—the type and amount of which could indicate different medical conditions--and to monitor that activity without needing to see the enzymes. RDAP combines FEED with a process called intrinsic signal amplification which boosts the electric signal to make it easier to detect. The combined techniques enable RDAP to find and identify bacteria down to extremely small quantities (4 bacteria per milliliter) without requiring culture.
In a previous proof-of-concept study, the team applied the device in contrived samples of E. coli in blood and achieved an 84-minute sample-to-result turnaround time in the combined bacteria detection-identification step compared to the current standard of care, which typically requires a 24-48-hour culture first. In antibiotic susceptibility testing, a 204-minute sample-to-result turnaround time was achieved compared to the 16-24 hours needed for culture-based methods.
“RDAP needs 88 minutes to perform the detection-identification step. Considering the 16-plus hours required by the standard lab procedure for this step, RDAP is already a near real-time diagnostic for the screening of specific bacterial species,” said study co-author Dr. Siu-Tung Yau, Professor of Electrical Engineering at Cleveland State University.
More recently, the team performed a clinical comparison of the device with that of current culture-based microbiology testing methods using blood samples obtained from patients at Saint Vincent’s Medical System in Cleveland, Ohio. The cohort contained both positive culture samples (confirmed bloodstream infections) as well as negative culture samples. In this study, the RADP achieved a diagnostic accuracy of 93.3% and 95.4% for detection-identification and antibiotic susceptibility testing, respectively.
Currently, RDAP can detect eight species of bacteria at once, representing 57% of known BSI-causing pathogens. The team’s next steps will be to continue building the device for additional species.
The researchers envision that by using RDAP to expedite time-to-diagnosis, it will also bring about a reduction in the use of broad-spectrum antibiotics at hospitals and could decrease patients’ overall length-of-stay.
“What we hope is to reduce the number of broad-spectrum antibiotics that our patients are receiving,” said Dr. VanEpps. “They may only have to receive one dose before transitioning to targeted therapy, whereas right now they typically receive anywhere from 4-10 doses. Additionally, many of these antibiotics can only be administered through an IV. But by transitioning to oral antibiotics earlier, we can help patients leave the hospital sooner.”
Studies Referenced
Shi, X., Sharma, S., Chmielewski, R.A. et al. Rapid diagnosis of bloodstream infections using a culture-free phenotypic platform. Commun Med 4, 77 (2024). https://doi.org/10.1038/s43856-024-00487-x
Shi, X., Kadiyala, U., VanEpps, J.S. et al. Culture-free bacterial detection and identification from blood with rapid, phenotypic, antibiotic susceptibility testing. Sci Rep 8, 3416 (2018). https://doi.org/10.1038/s41598-018-21520-9
Authors
Xuyang Shi (Electrical and Computer Engineering, Cleveland State University); Shivani Sharma (Rapidect Inc.); Richard A. Chmielewski (Saint Vincent Charity Medical Center); Mario J. Markovic (Laboratory Medicine, Saint Vincent Charity Medical Center); J. Scott VanEpps (Emergency Medicine, Macromolecular Science and Engineering, Biointerfaces Institute, Weil Institute for Critical Care Research and Innovation, University of Michigan); Siu-Tung Yau (Electrical and Computer Engineering, Cleveland State University)
Author Contacts
J. Scott VanEpps: jvane@med.umich.edu
Siu-Tung Yau: s.yau@csuohio.edu, syau@rapidect.com
Disclosures
The RDAP device was originally built at Cleveland State University. Dr. Yau is the president of Rapidect, Inc., which was developed to commercialize the device. Shivani Sharma is also an employee of Rapidect, Inc.
About the Weil Institute
The team at the Max Harry Weil Institute for Critical Care Research and Innovation 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 weilinstitute.med.umich.edu.