Simulated Blood Flow Device Demonstrates How Bloodstream Infections Begin

A computer model of how bacteria traveling through the bloodstream clumped together may explain how bloodstream infections resist antibiotics.

A team of University of Michigan (Anne Arbor, MI, USA) scientists demonstrated that bacteria can form antibiotic-resistant clumps in a short time, even in a flowing liquid such as blood. They built a device that closely simulates the turbulence and forces of blood flow, and added a strain of bacteria that is a common cause of bloodstream infections. Tiny aggregates, or clumps, of 10 to 20 bacteria formed in the flowing liquid in just two hours––about the same time, it takes human patients to develop infections.

The bioreactor used to produce the results is called a Taylor-Couette cell, and uses concentric cylinders, one of which is turned by a motor. Liquid growth medium was added to the reactor and then carefully controlled rotation produced eddies in the liquid that are similar to those of the blood. They then added Klebsiella pneumoniae bacteria, one of the most common sources of bloodstream infection. They tested two antibiotics that doctors often prescribe for sepsis: ceftriaxone and ciprofloxacin. Neither was effective at killing the clumped bacteria.

The clumps only formed when certain sticky carbohydrate molecules were present on the surface of the bacteria. The clumps persisted even when two different types of antibiotics were added suggesting that sticking together protects the floating bacteria from the drugs’ effects.
Mathematical models of the fluid dynamics of the bloodstream were created, and the conditions needed to promote bacterial growth. The models were tested using different types of containers and methods to simulate bloodstream conditions.

The clumps of bacteria were injected into mice and they stayed intact even after making many trips through the bloodstream. The clumps, about the size of a red blood cell, appeared to survive the filtering that normally takes place in the smallest blood vessels and defends the body against invaders.

The studies were described in the August 15, 2012, Journal of Infectious Diseases.

“This work demonstrates that if you let bacterial pathogens grow in fluid dynamic environments like they encounter in the bloodstream, they start to take on features that you see in patients,” said John Younger, MD, MS, professor in the department of emergency medicine at the U-M Medical School (UMMS; Anne Arbor, MI, USA) senior author of the new paper, and leader of a team of physicians, engineers, and mathematicians who have studied the origins of bloodstream infections for years. “The thing is to grow them in physical conditions that mechanically ‘feel’ like the motion of flowing blood.”

The chance of severe infection increases when someone is exposed to a source of infection, such as a central line catheter, that stays in place for days or weeks, giving tens of thousands of bacteria a chance to get into the bloodstream over time. Sepsis, which kills tens of thousands of people a year, can result when an exaggerated inflammatory response to a bloodstream infection triggers organ damage and failure.

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