Prevent biofilm formation to reduce the risk of hospital infections

Some hospitalized people feel worse than better. On average, 7% of all patients in industrialized countries have "nosocomial" infections. In intensive care units, the risk increases even more. This can lead to serious illness and life-threatening blood poisoning.

If patients are treated with invasive medical measures, hospital germs have a particularly easy time: if tubes are inserted into the body to ventilate, supply fluid or drain urine, infectious agents quickly get off the ground. We still do not know how these infections can be prevented. A team of Empa scientists and doctors from the Cantonal Hospital of St. Gallen is currently working on a project to reduce the risk of hospital infections.

The focus is on the badysis of biofilms, the accumulation of germs on surfaces that propagate, for example, in urinary catheters. However, designing materials to prevent the formation of biofilms requires knowing how germ growth actually occurs on surfaces. It is simply not possible to develop appropriate protective measures against the unknown. And it was here that medicine remained stuck in the darkness – it was largely unclear what exactly grew in a catheter.

The Empa researcher, Qun Ren, is looking for the secrets of polymer stents. In collaboration with the doctors of the St. Gallen Hospital, she examined samples of ureteral stents from nearly 90 patients. The use of a catheter or stent in the ureter is a common procedure, for example in the treatment of kidney stones. "However, if such a stent is used, the symptoms and urinary tract infections are quite common," says Ren.

This has also been observed in patients that she has examined: after a relatively short period of about three weeks in the body, calcium crystals (from the urine) have deposited in the tubes and the researcher also found an accumulation of bacteria in the samples. "Biofilms were formed on the surface of the material, from which we could grow live bacteria," she says.

The creature in the tube

Scientists believe that these biofilms are probably the most successful living things in the world: bacterial accumulations embedded in a self-produced and viscous matrix that behaves like a single organism. And they have existed for a long time before humans – biofilms are found in the oldest fossils known in the history of the Earth. Given their amazing survival strategies, it is not surprising that they persisted and developed under the worst conditions, such as urinary catheters.

Thanks to a wet layer of biopolymers, bacteria living together in biofilms are protected, mobile and connected to each other. They readily exchange useful genetic material, communicate through chemical signals, and signal to the surface that the deepest layers of their "colocation" suffer from hunger. The film is resistant to antibiotics and disinfectants and, if necessary, biofilms can send a group of pioneers to a new location to found other colonies, much like a metastatic tumor.

Clever like a gecko

What works in nature can go wrong in hospitals. The goal is to develop new materials for stents that reduce the risk of infection, for example. "A key event in the formation of a biofilm is when moving bacteria attach to a surface," Ren says. Some of the microorganisms use the same trick as geckos, which can hang on a window from the back: they exploit the van der Waals forces, the interactions between their own molecules and those of the surface. that they colonize. Other examples cover the surfaces of tubes and stents with a suitable coating, which helps them to settle on the surface. "To fight bacteria, we must therefore prevent the process of attachment," says Ren.

The prerequisite for the use of germ-resistant, usable materials and coatings is the continuous transfer of research results from the laboratory to the bedside. A material can only be proven if laboratory tests are as realistic as possible. The Empa researchers have therefore developed a multi-part laboratory model, whose conditions are as close as possible to those of the hospital.

Potential new catheter materials are rinsed with liquids in a bioreactor, as in the case of a true urinary stent inside the body. All isolated microorganisms are examined using confocal microscopy, bacterial culture and genetic badysis. At the same time, the surface of the calcium-crystal-coated material is characterized by X-ray badysis. "We can not produce new safe and highly effective materials that are resistant to bacterial biofilms if we know exactly what these microorganisms are capable of "said Ren.

Samples from the Cantonal Hospital of St. Gallen have been used to show exactly what is happening in the body with conventional catheters. Since all were patients with no evidence of infection prior to catheter insertion and stenting for only a short time in their body, all isolated biofilms were light, as expected. However, it has become clear that certain types of bacteria like to occur together. For example, some patients had harmful enterobacteria in their samples, while others had species of microorganisms such as lactic acid bacteria, believed to have a protective effect. The researchers will now study how these different "urotypes" are badociated with the risk of infection in the hospital. They also discuss the possibility of modifying surfaces differently according to certain subsets of patients. In the next step, the team plans to examine samples of long-term treatments and infected patients.