Sepsis Test Results in Hours, Not Days
Samuel Yang, MD, associate professor of emergency medicine, is accelerating the diagnosis of bloodstream infections, including a novel approach to quickly determine the susceptibility of bacterial pathogens to antibiotics.
Current sepsis testing is growth-dependent, requiring the causative pathogens to grow many generations to a detectable level before the diagnosis can be made and the best antibiotic choice determined.
This can take days.
Yang’s test analyzes bacteria at the single-cell level and is intended to deliver results within two to three hours. His approach captures live bacteria directly from whole blood and probes the genetic sequences within the bacterium for species identification, before tracking phenotypic features such as size, shape, and metabolism to assess the bacteria’s response to different antibiotics, even before the doubling time of the bacteria.
To work at such a minute scale, the test must be sensitive enough to first detect a low abundance of pathogens in the bloodstream and then capture a pathogen in its viable state. The test must also take into account intrinsic variability in pathogens as well as the host environment. Yang employs advances in microfluidics, microscopy, and machine learning to focus specifically on how pathogens would respond to different antibiotics in the host physiologic environment, accelerating the process to guide faster treatment decisions.
Yang and his team are also exploring how this technology could guide antibiotic treatment duration. Physicians can opt to treat infection with a narrow or broad spectrum of antibiotics, but current microbiological testing cannot guide how long to treat each infection. If duration is too short a patient may be undertreated. Too long, and you risk the emergence of drug-resistant bacteria. A test that reliably predicts how pathogens respond to antibiotics could also enable physicians to customize treatment duration for maximum impact and minimal risk.
Yang and the team have also made new progress in deconstructing how the body’s immune response plays a role in fighting bloodstream infection.
First responder cells or neutrophils provide the earliest warning of infection, and fight infection by committing NETosis or “cellular suicide.” Neutrophils expel their own DNA content to the extracellular space as a weblike structure called neutrophil extracellular traps (NETs) that captures and neutralizes a pathogen. Doing so most often causes the neutrophils to die. Yang’s group discovered that NETs are actually deoxyribozymes (DNAzymes) that can catalyze the formation of free radicals, which are shown to be the main drivers in pathogen killing but may also contribute to detrimental inflammations in response to bloodstream infection. His team is investigating how this fits into the sepsis diagnostic puzzle.
Yang received research funding for the project from the National Institutes of Health totaling $7.4 million, and is five years into the ten-year project. His work in precision diagnostics has the potential to impact the more than 1.7 million Americans who contract sepsis each year.
As part of this project, in 2024, Yang was also awarded an R21 grant from the National Institute of Allergy and Infectious Diseases (NIAID) for his project titled "Neutrophil Extracellular Traps are Free-Radical Generating DNAzymes."
Updated Spring 2024