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Simulator Shows Blood Stream Bacterial Formation

John Younger (University of Michigan)

John Younger (University of Michigan)

Researchers at University of Michigan in Ann Arbor and University of Colorado in Boulder devised a process to simulate the flow of blood in humans and demonstrate the growth of blood stream bacteria, as well as the limited effectiveness of antibiotics. The team of medical researchers, chemical engineer, and mathematician published their findings in the Journal of Infectious Diseases (Paid subscription required).

The team led by Michigan medical school professor John Younger (pictured right) addressed blood stream infections seen in hospitals, clinics, and nursing homes, and often affect more vulnerable populations such as older people, cancer patients, dialysis patients, and those who have had surgery or suffered severe injuries. The chance of severe infection, say the researchers, increases when someone is exposed to a central line catheter or similar source that stays in place for days or weeks, giving bacteria an extended chance to enter the blood stream.

In the past, Younger’s lab has built mathematical models to simulate the fluid dynamics of the blood stream, and the conditions needed to promote bacterial growth. For this research, the team used a bioreactor as a physical model to simulate human blood flow. The simulator, called a Taylor-Couette cell, has concentric cylinders, one of which is turned by a motor.

Younger and colleagues added liquid growth medium to the reactor, then controlled the rotation of the cylinder to produce eddies in the test liquid similar to those of the blood. To this medium, the team introduced Klebsiella pneumoniae bacteria, a common sources of blood stream infection.

The researchers found the bacteria can form antibiotic-resistant aggregates or clumps in a short time, even in a flowing liquid such as the blood. The clumps, of only 10 to 20 bacteria at a time, formed in two hours. This period, say the researchers, is about the same time it takes human patients to develop infections.

The clumps only formed, however, when certain sticky carbohydrate molecules were present on the surface of the bacteria. Nonetheless, when the researchers added to the test liquid two antibiotics used to treat sepsis infections — ceftriaxone and ciprofloxacin — neither was effective at killing the clumped bacteria. The team later injected the bacterial clumps in mice, which indicated the clumps stayed intact even after making many trips through the blood stream.

“The more you can reproduce what bacteria experience when they are in patients, the more you can understand what they are doing, and why they can cause an overwhelming infection in a whole organism,” says Younger. “Once we know how they behave, we can be intelligent about how to grab them out of the bloodstream, and filter them effectively.”

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