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From Bench to Bedside:
So Long Sepsis
Finding new ways to treat bloodstream infections

So Long SepsisResearch fellow Vladislav Dolgachev, Ph.D., is part of the team that hopes to find new ways of removing bacteria from the bloodstream, a primary cause of sepsis.

With one in 100 people developing a bloodstream infection each year, Dr. John Younger’s lab knows the importance of helping people treat and prevent these often deadly infections, especially among hospital patients.

Younger, associate chair for research in the Department of Emergency Medicine, leads a team of researchers with expertise in medicine, mathematics and chemical engineering that hopes to find new ways of removing bacteria from the bloodstream, a primary cause of sepsis. Their new laboratory findings show how bacteria act within the blood vessels of the body, and shed new light on the mechanics involved in filtering them so that they can be attacked by the immune system.

 

 

The Concept

So Long SepsisJohn Younger, M.D. (left) works in the lab with public health student Subramanyeswara Arekapudi.Bloodstream infections are a problem because most of the defenses that the body has built to fight infections were designed against things like sore throats and bladder infections—infections that happen somewhere specific in the body.

Bloodstream infections occur mostly when a patient is already ill and the body’s defenses aren’t working properly, or when therapy against another illness increases the likelihood of infection. The major problem with bloodstream infections is that “when bacteria are allowed to go anywhere, they have the opportunity to rewrite the rules,”Younger says.

Younger simplifies the complex issue: “It’s like a house fire—something that started in the fireplace that was easily controlled in the fireplace is now everywhere, and the strategies you would use to put out the fire in the fireplace don’t work when the entire house is on fire.”

A New Approach

So Long SepsisAlthough they’ve been around less than 100 years, antibiotics already have become less reliable for treating infections. Younger’s laboratory is searching for ways that don’t require antibiotics to treat infections and help the host defense.

To consider the problem another way, they’ve begun to imagine a bacterium’s experience during its life in a patient’s bloodstream. The organisms become part of the “heavy traffic” of blood cells and immune cells moving through the body. Most of the time, they are in parts of the circulatory system that are not able to fight them.

Laboratory studies have revealed some interesting findings. A series of mathematical rules can effectively describe the filtration process, even to the point of accurately predicting what happens in patients receiving chemotherapy. Being able to mathematically describe the phenomenon is a major step in not just understanding the illness, but knowing how to better design experiments to untangle the process by which bacteria persist or are removed from the blood.

Another important discovery is that bacteria in the bloodstream probably travel in packs. Younger explains when bacteria are mixed in the lab and grown in flasks, they typically grow as single cells; but in flowing blood, the bacteria stick together, changing the rules by which both host defenses and antibiotics attack them.

Treatment Tomorrow

The team is now looking at new therapies that might be used to rewrite the math of the problem—in the patients’ favor. Some could be available in less than five years, depending on the findings expected in the next year. Younger has a personal interest in finding treatments for bloodstream infections. His great grandfather died at age 21 from sepsis he developed when he had pneumonia, before the first use of antibiotics.

“The most important goal for all of us in this field is to try and reduce mortality, to try to reduce the burden this illness places on patients,” Younger says. - CF

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