Why a biofilm infection resists treatment
Biofilms are communities of microorganisms that grow on implants, catheters, wound dressings and dry hospital surfaces. They cause infections in hospitals and tolerate the antibiotics used against them. They are treated with several methods at once, and much of the research on them has yet to reach patients.
What a biofilm is and where it grows
Biofilms can be described as three-dimensional bacterial communities, often consisting of many types of microorganisms. An estimated 99% of bacteria on Earth live in a biofilm. Most of a biofilm is made up of exopolysaccharides (EPS), the slimy substance that bacteria secrete. The EPS creates an ideal microbial ecosystem by neutralising harmful conditions, aiding gene transfer and nutrient exchange, keeping enzymes close to the bacteria and providing a means of communication known as quorum sensing. As a biofilm matures, pieces of it detach and colonise other areas. Unattached biofilm aggregates have been associated with chronic infections, such as cystic fibrosis, a genetic disease characterised by biofilm infections in the lungs.
Like most bacterial colonies, biofilms thrive on wet surfaces, which is why they are easily found on implants, catheters and wound dressings. Biofilms can also survive in dry conditions, and one study found dry-surface biofilms on 95% of disinfected items in hospitals.
Infections biofilms cause in hospitals
In Europe, infections caused by biofilms in hospitals alone affect more than four million patients a year, leading to 37,000 attributable deaths and contributing to an additional 110,000. In the United States, the Centers for Disease Control and Prevention estimated that at any given time one in 31 hospital patients has a healthcare-associated infection (HAI). These numbers are not the consequence of a disregard for hygiene by hospital staff, but indicate how ubiquitous biofilms are and how difficult they are to eliminate. Despite extensive research on biofilms in the two decades to 2022, they still had the upper hand in hospitals and clinics and posed a significant medical challenge.
Why antibiotics fail against biofilms
Biofilms are not uniform: they hold bacteria at different stages of growth and in varied metabolic phases. Typically, the bacteria at the outer edges of a biofilm are the most active, as they have plenty of accessible oxygen and nutrients. But the dormant, slow-growing bacteria in the nutrient- and oxygen-depleted zones within the biofilm are the key to its success. Antibiotics and other antimicrobial agents attack the outer layers of the biofilm, leaving the deeper layers intact. Given how often antibiotics are used in healthcare, the bacteria become increasingly tolerant to ever-rising concentrations. Under laboratory conditions, bacteria in biofilms were 100 to 1,000 times more resistant to antibiotics than free-living planktonic bacteria.
This tolerance is a particular threat in treating patients, because a higher dose of antimicrobials or a stronger biocide may cause unfavourable side effects. For medical devices and instruments, using strong oxidisers for an extended time is seldom possible.
How biofilms are treated
In 2022, the approach was to combat biofilms with multi-targeted therapies. Because of the complex structure of a biofilm, no single method reverses its growth in every case, as in the modern-day treatment of tumours.
Coating the surface of medical implants or impregnating wound dressings with, for example, silver nanoparticles is a method of discouraging biofilm growth before it begins. Similarly, the surfaces of implants and catheters can be re-engineered to resist bacterial colonisation. Ideas for preventing bacteria from sticking to medical devices include changing the surface charge, increasing surface roughness by etching nanoscale structures and making the surface more hydrophobic.
One way of disrupting biofilm structure is with physical methods, such as high-velocity sprays, which may contain antibiotics or other common biocides. At home, a dental water jet has proved very effective at removing oral plaque biofilm. Once a biofilm has grown, substances that target the EPS help to break it up. The components of the EPS can be hydrolysed using enzymes or disrupted mechanically with lasers or ultrasound. Combining these methods with antimicrobials is crucial to keep the biofilm from growing back.
How far biofilm research has reached patients
In 2022, many solutions for limiting biofilms in health facilities were still at the laboratory stage. Their results were convincing, but there were far fewer follow-up experiments in vivo or with human cell models, which is why very few new strategies for combating biofilms advanced to clinical trials. Of the clinical trials being conducted in 2022, most concerned oral biofilms, while biofilms in HAIs and in chronic diseases were under-represented. Despite more than 40,000 papers on biofilms by the end of 2019, many studies still grew bacteria in Petri dishes, or even analysed planktonic bacteria, instead of studying biofilms as they occur in real life. One writer holds that a multidisciplinary approach to biofilm research is essential to fill the gap between molecular biology and medicine, and that teaming up with start-ups that aim to bring antibiofilm products to market also pushes basic science forward and fuels innovation in the field. In this view, calling for more research is not enough: integrative research on biofilms in healthcare settings is what will ultimately decrease the likelihood of infection.