Infectious Diseases, Microbiology, Point of Care

What Are Biofilms? How Do They Cause Antimicrobial Resistance (AMR)?

Author Chandana Balasubramanian , 22-Aug-2023

A biofilm is a layer of microbes that grows on a surface or structure. The simplest example of one is plaque, the sticky layer of bacteria that grows on our teeth.

 

In general, some biofilms are more problematic than others.

 

When biofilms form on medical devices and catheters in our bodies, they can cause severe infections that are hard to treat. This is because bacteria in them are protected by the slimy biofilm matrix, which makes it harder for antibiotics to do their job.

 

According to the US National Institutes of Health, biofilms are responsible for over 80% of microbial infections in the body. Many of these are resistant to antibiotics and may even cause severe chronic infections.

 

Apart from the toll on the nation’s health, this type of resistance can get expensive. In 2017, it was estimated that 78.2% of chronic wounds had biofilms associated with them, costing the US healthcare system almost $281 billion.

 

Here, we delve into the intricate world of biofilms – how they are formed, where they are found, and how these layers  contaminate medical devices, causing serious health complications and infections. We will also explore how their formation can lead to formidable resistance against antimicrobial drugs.

 

Understanding a biofilm and its formation

Biofilms are fascinating and complex structures that have significant implications in the medical field. Microorganisms, such as bacteria, fungi, and viruses, aggregate to form slimy coatings on surfaces.

What is a biofilm?

A biofilm is a slimy layer of bacteria or other microorganisms that grow on a surface. The bacteria group together and build colonies inside a slimy matrix that offers safety in numbers (for the microbe) and protection from outside elements because of the slimy enclosure. The matrix is made of extracellular polymeric substances (EPS). The EPS acts as a protective shield for these organisms against environmental threats.

These biofilms are not just physical structures, they also allow microorganisms to thrive by facilitating nutrient exchange and genetic material transfer. Think of them like towns or cities of bacteria.

How are biofilms formed?

Biofilms start when a layer of free-floating bacteria attaches to a surface, most often in the presence of moisture. After this, the bacteria release EPS, the gel-like slime that strengthens their hold on the surface.  The third stage is maturation, where cells multiply and form elaborate mushroom-like structures complete with water channels that allow nutrients and waste to flow within. Eventually, in the dispersion stage, some cells leave the biofilm and colonize new areas, thus repeating the cycle.

This ability to form biofilms allows these otherwise harmless organisms to survive harsh conditions like exposure to antibiotics or our body’s immune system response. This protection makes it harder for healthcare professionals to treat infections caused by them.

Understanding how biofilms form can help develop strategies to prevent their growth on medical devices and implants and reduce infection rates. This would be especially beneficial in surgical procedures where contamination due to biofilms often leads to failure or complications post-surgery.

Are biofilms easy to find?

Biofilms are found everywhere. They can thrive in a wide range of habitats – from the deepest parts of oceans to the highest mountain peaks, and even inside our bodies. This is due to their unique ability to adhere to many types of surfaces and survive under diverse environmental conditions.

Where can you find biofilms?

You might be surprised by how common biofilms are. For instance, that slimy layer on rocks in rivers or streams? That’s a biofilm. The plaque on your teeth if you don’t brush regularly? Also a biofilm. In fact, biofilms play crucial roles in many ecosystems like wastewater treatment plants where they help break down organic matter.

    • Rivers & Streams: Biofilms form on submerged rocks providing habitat for other aquatic organisms.
    • Your Mouth: Dental plaque is a type of biofilm that could lead to tooth decay if not removed regularly.
    • Hospitals: Medical devices such as catheters and implants often become contaminated with biofilms leading to healthcare-associated infections (HAIs).

 

What species and types of microbes form biofilms?

The diversity among biofilm-forming species is staggering. Bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus are well-known culprits when it comes to hospital-acquired infections, but fungi like Candida albicans also form robust biofilms, which contribute to systemic fungal infections. Recent studies suggest viruses may also participate in creating these microbial communities, which further complicate eradication efforts.

Medical implications of biofilm formation

Biofilms pose significant challenges in healthcare, especially when they develop on medical devices and implants.

Biofilms contaminate medical devices

Medical devices such as catheters, heart valves, joint prostheses, or even contact lenses provide an ideal environment for bacterial biofilms like Pseudomonas aeruginosa, a common gram-negative bacterium known for its ability to form biofilms. Once attached, the bacteria produce extracellular polymeric substances (EPS) and create a slimy matrix that protects them from external threats, including antimicrobial agents. This leads to contamination of these medical devices with pathogenic bacteria, posing serious health risks.

Impact of biofilms on surgical procedures

Surgical procedures that involve medical device implants have seen greater failure rates due to infections caused by bacterial biofilms. What makes biofilms more dangerous is that it is often impossible to detect the formation of these complex structures until symptoms become severe. This leads to systemic infection or sepsis in patients.

A study showed that Staphylococcus aureus can colonize orthopedic implants, leading to osteomyelitis – an infection of bone tissue caused by biofilm formation.

Medical complications associated with biofilms

  • Infections: Post-operative wound infections are a major concern associated with surgical procedures where pathogens form biofilms, making it hard for antibiotics to reach their target effectively.
  • Persistent Inflammation: Biofilm-associated inflammation can persist long after surgery, leading to chronic inflammation that further complicates the patient’s recovery process.
  • Increased Hospital Stay: The presence of robust biofilms may increase hospital stay duration due to the risk of complications related to secondary infections. These types of severe infections can adversely impact a patient’s quality of life and escalate overall public health costs.

Key Takeaway: Biofilms pose significant challenges in healthcare, especially when they develop on medical devices and implants. Bacteria attach to surfaces of these devices and form robust biofilms that protect them from external threats. This can lead to contamination and pose serious health risks like post-operative wound infections or persistent inflammation.

Biofilm-related complications can increase hospital stay duration, escalate overall public health costs, and even cause severe systemic infection or sepsis.

 

Antibiotic resistance and persister cells inside biofilms

Dealing with biofilm infections is like trying to fight a hydra – if you cut one head off, two more may grow back. Antibiotics often struggle to penetrate biofilms due to their resistance-inducing properties. This resistance is due to a combination of physical barriers, altered metabolic states, and genetic adaptations.

What makes biofilms so resistant to antibiotics?

The biofilm’s extracellular matrix (EPS) acts like a fortress, preventing antibiotics from penetrating deeper layers. Bacteria within biofilms also have slower growth rates and altered metabolic activity, making many antibiotics ineffective. On top of that, bacteria within biofilms frequently exchange genetic material, spreading resistance genes faster than gossip.

The role and impact of persister cells in antibiotic-resistant biofilms

Persister cells are specialized bacterial cells that are usually dormant in a bacterial colony and highly resistant to antibiotics. They are like sleeper agents, waiting for the right conditions to reactivate and cause trouble. These specialized bacterial subpopulations enter a dormant state in response to stress conditions (like exposure to antibiotics). While they don’t actively contribute to disease symptoms during this phase, they can reactivate and cause infection relapse once favorable conditions return.

Combining structural defenses, physiological alterations, and persister cell populations makes it incredibly difficult for traditional antimicrobial therapies to eliminate infectious biofilms.

 

How can research help? 

The medical world is not standing still in the face of challenges posed by biofilms. Research and innovations are continuously being pursued to prevent biofilm formation on medical devices and implants, with the ultimate goal of reducing infection rates.

Innovative techniques to prevent biofilm formation

One promising area of research involves developing surface coatings that can resist bacterial adhesion, thereby preventing biofilm formation from the get-go. For instance, antimicrobial peptides (AMPs), which are naturally occurring proteins with antibacterial properties, have been explored as potential coating materials for medical devices.

Another innovative approach is using light-activated therapies like photodynamic therapy (PDT). PDT uses a photosensitizing agent that becomes toxic to bacteria when exposed to specific wavelengths of light. This technique has shown promise in eradicating biofilms without promoting antibiotic resistance.

Latest breakthroughs and discoveries about biofilms

New discoveries also continue to emerge in this field. Recently, scientists discovered that certain compounds called furanones could interfere with quorum sensing – a communication process among bacteria necessary for forming robust biofilms – thus inhibiting their growth.

Bacteriophages or “phages,” viruses that infect bacteria, are another exciting discovery. These phages can be engineered to produce enzymes known as depolymerases which break down the protective matrix surrounding a biofilm making it easier for antibiotics to reach and kill off resident microbes.

All these efforts underline an important point: while dealing with biofilms may be challenging due to their complexity and resilience, through persistent research we are slowly but surely finding ways around them – ushering hope towards significantly improving patient outcomes post-surgery involving device implantation.

Key Takeaway: The medical industry is actively researching and innovating to prevent biofilm formation on medical devices and implants, with promising techniques including surface coatings that resist bacterial adhesion such as antimicrobial peptides (AMPs) and light-activated therapies like photodynamic therapy (PDT).

Recent breakthrough discoveries include compounds called furanones that can inhibit bacterial growth and bacteriophages (phages) that produce enzymes that break down the protective matrix surrounding a biofilm, making it easier for antibiotics to reach.

 

FAQs about biofilms in medicine

What infections are caused by biofilms?

Biofilms can form a variety of infections and medical issues, including:

  • Periodontitis from dental plaque
  • Cystic fibrosis
  • Urinary tract infections (UTIs)
  • Kidney stone infections
  • Inflammation of the heart (infective endocarditis)
  • Ventilator-associated pneumonia (VAP)
  • Chronic inflammation
  • Osteomyelitis (inflammation of the bone or bone marrow), and much more.

 

Can antibiotics be used to treat biofilms?

Biofilms are especially challenging to treat because they are often polymicrobial with different types of microbes thriving under one slimy biofilm. Research shows that the same bacteria showed high resistance to antibiotics inside a biofilm but could be treated with the same antibiotic when outside a biofilm.

This shows that biofilms offer intense protection – even 1000 times greater antibiotic resistance than when the microbe is found in nature without one. This is because various complex structures and processes work together to provide protection for microbes under a biofilm, even when high doses of bacteria are present. So, currently, surgeons use strong jets to clean surgical sites and medical device manufacturers coat their devices with materials to help prevent infection. Hopefully, we can have antibiotics that can penetrate strong biofilm barriers soon.

 

Conclusion

Biofilms are complex communities of microbes that play a significant role in many aspects of our lives. From dental plaque to industrial pipelines, these slimy layers can be found wherever there is a surface, moisture, and a supply of nutrition. Because biofilms provide a high level of protection for bacteria and microbes within the slime, they pose strong challenges in healthcare settings. They can cause serious illness, persistent infections, and antibiotic resistance. Understanding the formation and behavior of biofilms is crucial for developing effective strategies to control and manage them.

 

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References

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[7]    N. Kavanagh et al., “Staphylococcal osteomyelitis: Disease progression, treatment challenges, and future directions,” Clin. Microbiol. Rev., vol. 31, no. 2, 2018.

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[9]    J. T. C. de Pontes, A. B. Toledo Borges, C. A. Roque-Borda, and F. R. Pavan, “Antimicrobial peptides as an alternative for the eradication of bacterial biofilms of multi-drug resistant bacteria,” Pharmaceutics, vol. 14, no. 3, p. 642, 2022.

[10]    N. R. Luke-Marshall, L. A. Hansen, G. Shafirstein, and A. A. Campagnari, “Antimicrobial photodynamic therapy with chlorin e6 is bactericidal against biofilms of the primary human otopathogens,” mSphere, vol. 5, no. 4, 2020.

[11]    S. Liu, H. Lu, S. Zhang, Y. Shi, and Q. Chen, “Phages against pathogenic bacterial biofilms and biofilm-based infections: A review,” Pharmaceutics, vol. 14, no. 2, p. 427, 2022.

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Author
Chandana Balasubramanian

Chandana Balasubramanian is an experienced healthcare executive who writes on the intersection of healthcare and technology. She is the President of Global Insight Advisory Network, and has a Masters degree in Biomedical Engineering from the University of Wisconsin-Madison, USA.

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