Sepsis is one of the most pressing infectious diseases physicians have to address today. It accounts for more deaths than cancer, HIV, stroke, acute MI and trauma, and is the leading cause of mortality in hospitals. Sepsis is also the leading cause of ICU admissions and the most expensive hospital admission.
Because of high mortality rates from sepsis and other bloodstream infections, physicians cannot wait to receive a positive blood culture to begin treatment, said Yang, MD, FACEP, associate professor of emergency medicine. Instead, they must rely on best guesses and broad-spectrum antibiotics, which contribute to the scourge of antibiotic resistance. Currently, doctors wait two to three days for cultures to grow and reveal the specific strain of the blood-borne pathogen to better target therapy.
“We need a better diagnostic tool,” he said. “Infectious disease is one of those medical conditions where we are still relying on century-old diagnostic tools based on classic microbiological methods that take days for results. They are essentially of no use for emergency care. We need something to work in the acute care timeframe, which is four to six hours.”
At Stanford, Yang divides his time between patient care in the ED and research in his lab. In collaboration with other departments across Stanford University and other institutions, Yang’s team is developing a test that could identify sepsis within hours, rather than days.
Rapid testing platform
Yang’s lab is leveraging advances in microbiology, engineering and computer science to develop a clinically actionable solution. Instead of relying on the growth of blood cultures that can take days, this new testing platform analyzes genetic sequences within the bacteria and cellular response to antibiotics to make a targeted sepsis diagnosis.
The detection system has the potential to supplant traditional blood culture. It would be broad enough to pick up any microbial pathogen that ends up in the bloodstream. The goal, said Yang, is to create a rapid test that would identify the infection down to the species level and also provide antibiotic susceptibility to the detected pathogens.
Results would come in hours, not days. While physicians would still need to treat broadly with the first dose of antibiotics, Yang is hopeful that this new testing platform could inform the second and future doses of antibiotics, to more precisely target the infection. A more refined and quick diagnostic tool would also help at a public health level, by containing potential outbreaks from contagious pathogens early and decreasing the emergence of drug resistance to antibiotics.
“The technology we’re using incorporates single-cell microfluidics, which allow us to detect and resolve the causative pathogens down to a single bacterium,” he said. The new testing platform interrogates the microbial DNA sequences using their DNA melt signatures to help identify the organism, and a combination of microscopy and molecular technologies to monitor the cell viability to antibiotics.
The testing is still in the development phase, but all of the core technologies have been developed and have shown early proof of concept, Yang said. Yang’s team is now developing the prototype, essentially bundling these disparate technologies together in a box.
“We’ve tested all of the individual components such as being able to process the blood, being able to isolate the pathogens efficiently, being able to analyze them at a single-cell level reliably, being able to differentiate the DNA melt signatures so we can confidently identify each species, and then being able to look at various viability features to determine whether or not these pathogens are susceptible to different antibiotics,” he said. “Now it’s a matter of integrating them into a consolidated platform.”
The technology is three to five years from clinical validation, but the platform has far-reaching potential, said Yang. It is being designed to be able to broadly detect any blood-borne pathogen, and flexible enough to be used with other sterile body fluids such as urine and cerebral spinal fluid, and possibly non-sterile specimens such as sputum and stool.
“This new technology will save lives,” said Yang. “In sepsis, every hour delay in treatment increases mortality by close to ten percent. The earlier you can give the most appropriate antibiotics, the greater mortality decreases.”