Sepsis, a life-threatening condition that stems from the body trying to fight off an infection, plagues over 1.5 million patients a year in the U.S. alone, with one in three deaths recorded in the hospital attributed in part to sepsis. Despite the severity of the condition, which can kill in as little as 12 hours, it takes between two and seven days for most traditional approaches to definitively identify sepsis-causing bacteria in blood infections.
A team led by an engineer at Penn State has developed a way to condense the days-long diagnosis timeline to just hours. The new approach rapidly grows the bacteria present in collected blood samples, intermittently analyzing the samples with advanced techniques that help scientists identify the specific pathogens causing infection. The researchers reported in a paper published today (Aug. 26) in Science Advances that their approach facilitated faster diagnosis and could help clinical decision-making that avoids worsening antibiotic resistance in the bacterial strains causing infections.
"For a physician, 'what actually caused this infection and how should it be treated?' are the most important questions when it comes to the timely management of a bloodstream infection," said corresponding author Pak Kin Wong, professor of biomedical engineering and of mechanical engineering. "We are developing a comprehensive diagnostic platform that rapidly tells physicians both the specific bacteria causing a bloodstream infection, as well as the ideal antibiotic to treat the infection, before sepsis ever sets in."
With a bloodstream infection, it is critical to find and neutralize the cause as quickly as possible, before it triggers a septic response from the body, Wong explained. Physicians must not only detect the presence of bacteria - they must also identify the specific pathogens, as well as the best antibiotic for treatment. The dire stakes of a false positive or negative complicate this further, as every hour counts when treating a bloodstream infection, Wong said.
"This is not like a COVID test, where we are checking to see a specific virus is present in a patient's system," Wong explained. "Many different bacteria can cause sepsis, and they may respond differently to treatment. Therefore, analysis must be thorough to ensure the best treatment is prescribed."
Bloodstream infections are responsible for about 40% of all sepsis cases that lead to hospitalization. The complex biological makeup of the blood and the low pathogen loads needed to trigger sepsis make pinning the cause of a bloodstream infection time-consuming. To identify the bacteria causing a bloodstream infection, current best practices require bacterial culturing: Blood samples are enriched over a few days so that present bacteria grow to measurable levels. Then, technicians further analyze the samples to identify the specific bacteria, a process that adds another day or two to diagnosis.
Streamlining bloodstream infection diagnosis is not a novel idea, with several commercial products offering culture-free blood testing already on the market. However, to reduce diagnostic time, these products provide less comprehensive and less sensitive readings, Wong said.
To accelerate diagnosis without sacrificing accuracy, the team had to rethink culturing. Traditionally, bacterial growth in a cultured blood sample is measured through the carbon dioxide released by the bacteria. When this change in carbon dioxide levels confirms the presence of pathogens, bacteria are separated from the blood sample and analyzed. The team's new approach, called STREAM, fast-tracks this culturing by facilitating rapid bacterial growth, while isolating and analyzing the pathogens inside simultaneously - blood samples are mixed in a specialized "broth" that separates whole blood cells from the individual bacteria found in the sample during culturing.
