Urinary catheters are ubiquitous, dating back to rigid devices developed around 1500 B.C. and modified for flexibility by Benjamin Franklin in 1752, when he wanted to assist his ailing brother who suffered with chronic kidney stones.
In addition to the discomfort they cause, urinary catheters—medical devices used to empty the bladder—are also responsible for a plethora of infections, even when infused with antimicrobial agents. Ana Flores-Mireles, Hawk Assistant Professor in the Department of Biological Sciences, at the University of Notre Dame and collaborators are seeking to change that, and invented a catheter with a special coating that may reduce catheter-induced urinary tract infections (CAUTI).
The new catheter, described in a recent paper in eLife, could potentially improve quality of life and reduce deaths related to bloodstream infection caused by CAUTI.
“We didn’t just want to make a new technology; we want to understand how the catheter works inside the body,” said Flores-Mireles, who is also affiliated with the Harper Cancer Research Institute. “What happens once the catheter gets inside the bladder? What is the patient's response to the urinary catheterization? And how does this promote infection?”
They have found that the inflammation caused by the catheter induces release of proteins from the bloodstream into the bladder. One specific protein, fibrinogen, was found to be responsible for promoting bladder and catheter colonization by a number of pathogens.
Flores-Mireles and co-principal investigator Caitlyn Howell, assistant professor of biomedical engineering at the University of Maine, received a five-year, $2 million grant in June 2021 from the National Institutes of Health to develop and study the efficacy of this liquid-infused silicone catheter. The novel coating prevents deposits of fibrinogen from building up on the catheter surface. Fibrinogen is a healing agent that aids in blood clotting, but within the catheterized bladder can act as a basket, collecting more microbes and propagating infection.
In the paper, the researchers demonstrated two different ways that liquid-infused silicone catheters inhibited pathogens such as bacteria and fungus from colonizing the devices and the inside of the bladder. In addition to preventing the adhesion of fibrinogen, the research team’s modified catheter is more flexible than traditional ones. This reduces scratches inside the bladder. Scratches, cuts and scrapes all signal the liver to produce more fibrinogen that is then readily available in the bloodstream.
Some catheters are coated with antimicrobial agents. Though the catheters ward off infection under laboratory conditions, Flores-Mireles said, they don’t work within the bladder because the fibrinogen and other proteins adhere to the surface of the catheter and prevent the coating from reaching the infection.
“Protein deposition is not uniform, therefore, in regions of the catheter where there is no fibrinogen or other proteins, the antimicrobial agents will be released, but there is a smaller concentration,” she said.
This sub-inhibitory concentration, an amount too small to kill or prevent the growth of bacteria or fungus, eventually could cause antimicrobial resistance that may prevent the medication from killing the bacteria or fungi in the future.
Flores-Mireles’s lab conducted the research using mouse models. She and Marissa Jeme Andersen, a fourth-year graduate student who is the first author on the paper, used the liquid-infused catheters and compared results with a control group using regular catheters. They then analyzed the bladders for various microbes, swelling, and fibrinogen in the bladder lumen – the hollow space that holds the urine.
The new catheters proved effective at keeping down several different types of microbes, as well as reducing swelling around the lumen.
The technology, which takes into account the patient’s response rather than focusing solely on the pathogens, could revolutionize the lives of people who have to use catheters long term.
“The use of urinary catheters is rising because we have a large aging population, and there are many diseases and conditions that could land you in the hospital for surgery,” Flores-Mireles said. “But we have created a catheter that not only prevents protein deposition and thus microbial colonization, but also causes less inflammation and without promoting antimicrobial resistance.”
Other researchers on the paper include ChunKi Fong from the University of Maine, as well as Alyssa Ann La Bella, Jonathan Jesus Molina, Alex Molesan, and Matthew M. Champion, all from the University of Notre Dame.
Originally published by at science.nd.edu on March 29, 2022.