Understanding The Impact Of Biofilm In The Diabetic Foot

Over the last several years, the concept of biofilms and their relationship to wound healing and chronic wounds has gained popular interest. We have known about the normal microflora of humans, which form biofilms that are harmless and even beneficial to their host. These biofilms are located on the surface of medical devices such as orthopedic implants.

However, due to various factors, these biofilms can become pathogenic, causing disease processes as well as impairing healing in wounds. This can be readily visible in dental patients with periodontal disease and plaque (oral biofilm), and in burn patients, who commonly develop Pseudomonas aeruginosa infections, one of the Gram-negative bacteria very adept at forming biofilm.¹

While it is not the intent of this article to provide in-depth detail on the nature of biofilms, it is meant to increase basic understanding and awareness of biofilm as it contributes to the challenges we face in wound care today.

So what is a biofilm exactly? Leaper and colleagues described biofilm best as a complex microbial community, consisting of bacteria embedded in a protective matrix of sugars and proteins (glycocalyx).² Phillips and coworkers described biofilms at a more basic level when they defined biofilm as bacteria embedded in a thick, slimy barrier of sugars and proteins.³ Biofilms do not comprise a lone bacterium but rather groups of bacteria. These biofilms are very challenging because of the unique characteristics they possess.

One important ability of the biofilm is termed quorum sensing. This refers to the bacteria’s capability to communicate with each other through the production of signaling molecules.⁴ While more research is needed in this area, quorum sensing has been associated with antibiotic resistance. This communication allows the bacteria to coordinate their gene expression once a quorum has been reached, enabling bacteria to adapt to various environmental changes.

Another important characteristic of the biofilm is that the community is in a constant state of mutability. The mature biofilms shed fragments of planktonic bacteria that can then migrate to other uncolonized surfaces and begin the formation of new biofilm. This subsequently increases the risk of local or distant infection.² It is also well known that the bacteria in biofilm can slow down our own immune system. This is due to the specific properties of the biofilm matrix that are antiphagocytic, causing decreased efficiency of the body’s micro- and macrophages at ingesting the bacteria.¹

How Biofilm Complicates Wound Healing In The Diabetic Foot

Patients with diabetes have increased challenges of wound healing due to the comorbidities associated with the disease process, including neuropathy, peripheral arterial disease, nephropathy and retinopathy. Diabetic wounds halt in the first stages of wound healing as wounds are chronically arrested in the inflammatory phase. Necrotic tissue, foreign material and bacteria produce matrix metalloproteases that impair cellular function.⁵ Biofilms appear to be a major contributing factor to these chronic inflammatory changes in the wound bed.

In a 2008 study assessing wound tissue biopsies with electron microscopy, James and colleagues suggested 60 percent of chronic wounds have a biofilm versus 6 percent in acute wounds.⁶ This is highly suggestive of contributing to the delay in wound healing.

The treatment of chronic wounds with the suggestion of biofilm involvement is very challenging for the wound care specialist. Typically, biofilms are microscopic. There has been some conjecture that suggests if one leaves wounds with biofilms undebrided for a sustained period of time, the biofilm can become thick enough to be visible and the wounds would appear to look more gel-like and shiny.⁷

However, one may confuse biofilm with wound slough, which is somewhat opaque, more viscous and yellow (see top photo at right). Hurlow and coworkers have also suggested there may be a link between biofilm and slough as biofilms stimulate inflammation, which in turn increases vascular permeability, the production of wound exudate and subsequently the buildup of fibrin slough.⁷ This has yet to be clearly defined.

Keep in mind that not all wounds are infected. They can be contaminated or even colonized but not necessarily to the point of critical colonization where the wound tissue is damaged, healing is impaired and local infection is present. The challenges we face with biofilm are complicated by the fact that one cannot adequately culture biofilm with standard clinical microbiology tests. These tests optimize the culture of planktonic bacteria and not bacteria as they form in a biofilm. Biofilm cultures require special cultivation techniques (outside of the scope of this article) to identify the organisms causing the chronic infection.⁸

A Closer Look At Debriding Biofilm

It has been generally agreed upon that the best method in the treatment of biofilm is removal through debridement. The rationale for serial debridement is to activate senescent cells, stimulate the release of growth factors, remove inflammatory factors and reduce bioburden.⁹ We can extrapolate that regular debridement can provide a reduction in biofilm regrowth by removing necrotic and contaminated tissue to allow for healing.

Wolcott and colleagues looked at biofilms in wounds of patients with critical limb ischemia (CLI).¹⁰ They noted that the drier environment of the ischemic wound bed may not allow a biofilm to fully mature for five to seven days, which could explain why once-weekly debridement is usually enough to manage wounds in patients with CLI.

As of yet, there is not one best standardized method of debridement or frequency of debridement established for the treatment of biofilm. It has also been suggested that wound cleansing plays a role in the reduction of biofilm. Wound cleansers work by mechanical removal of bacteria and debris, and may disrupt the biofilm. New wound cleansers are being developed in this category but more studies are necessary to evaluate this promising technology.³ Broad spectrum antimicrobial dressings are also an appropriate form of treatment since the biofilm is polymicrobial.

Finally, as always, be attuned to the basics of wound healing, including infection (dictating the use of oral antibiotic therapy); offloading (to reduce and/or prevent pressure on the wound); vascular disease (necessitating surgical intervention to improve flow); and moisture balance. As there is not one definitive measure to determine the resolution of biofilm, one must look at progression toward healing as a good clinical indicator.

In Conclusion

Patients with diabetes, especially those with poorly controlled diabetes, pose unique challenges in the treatment of ulcerations. This population is at high risk for developing chronic wounds, which puts them at an even higher risk for the development of biofilm. While there is still much to learn about the nature and treatment of biofilms within the wound care setting, it is of the utmost importance to be aware and acknowledge biofilm’s existence in order to best formulate treatment regimens for our patients burdened with ulcerations.

Dr. Zmuda is an Associate Professor in the Sections of Vascular Surgery, Orthopedic Surgery and Endocrinology at the University of Chicago.

References
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10.    Wolcott RD, Rhoads DD. A study of biofilm-based wound management in subjects with critical limb ischaemia. J Wound Care. 2008; 17(4):145-155.