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Outliers: Reexamining Wounds That Fail to Heal

January 2019

A study from Queensland University of Technology in Australia (Brisbane, Australia) and the University of Southern California (Los Angeles, CA) revealed diabetes-related lower extremity complications are now among the top 10 leading causes of health disability in the world, ahead of chronic kidney disease, ischemic heart disease, and cardiovascular disease.1-4 Further analysis of the diabetic cohort predicted this population will produce as many as 148 million foot ulcers in their lifetime, making diabetic lower-extremity complications the leading cause of infection, hospitalization, and amputation worldwide.1 The most astounding revelation from the study is not the fact that diabetic limb complications have attained such a predominant position in global health issues, but rather that the leading cause was infection and a perceived persistent failure to follow evidence-based medicine (EBM).3 Studies2-4 have proven repeatedly that the use of EBM often is the determining factor between a healed and nonhealed wound and is strongly related to outcomes; however, the prevalence of EBM practice has not diminished the persistent threat of infection.  

Although what constitutes best evidence for treating wounds continues to be debated, infection remains the elephant in the room. Whether the controversy surrounds high bioburden or critical colonization or infection, the outcome is the same — a nonhealing wound. 

According to a 2014 study,5 >99% of all wound bacteria exist within a biofilm construct, yet progressive biofilm treatments continue to be overlooked in lieu of outdated or ineffective options. Evidence is mounting in favor of a dramatic assumptive shift to early and aggressive biofilm intervention implemented during wound bed preparation and performed throughout the wound healing continuum. These days, practice of EBM is hard to avoid, especially with every move scrutinized and examined under a performance microscope. Wound care providers are exasperated; even when they think they have applied EBM and considered every possible treatment, modality, and creative combination of advanced therapies in their toolbox at the suggested intervals (including serial debridement), they fail to achieve the same outcome from wound to wound. Laying blame for treatment failures on poor application of EBM may be a way to avoid one of the real issues behind the escalation in nonhealing wounds: a science-based approach to biofilm-directed wound care. 

The lurking threat of biofilm impacts >90% of chronic wounds and 6% of acute wounds.6 With biofilm’s structure protecting as much as 99% of all wound bacteria, without biofilm-directed care, a wound is often life-long and life-ending.5,7 Admittedly, the majority of wounds we treat (such as diabetic ulcers) have etiologies that are fairly straightforward, but other wound etiologies often are varied and not well understood. A new level of biofilm understanding has connected root cause factors from wound to wound, acknowledging the pathogenic trail of inflammation linking a failure of wounds to heal to reactive biofilm responses.8 One Australian plastic surgeon has recognized that biofilms cause and stimulate scar tissue in as many as 60 000 breast surgery patients a year; biofilm gains access to the implant during surgery and forms a thin film over the implant, leading to inflammation and causing scar tissue and capsular contracture.9 From battlefield trauma wounds and burns to less studied but equally as devastating conditions such as recurring acne, hidradenitis suppurativa, recalcitrant scalp folliculitis, and the nefarious atrophie blanche (a background diagnosis for 9% to 38% of venous leg ulcers), there is a common inflammatory source, raising the question, Could part of the problem be biofilm and part of the healing solution be biofilm-directed care?7,8 

Biofilm, with its partner inflammation, stalls healing and left unchecked often progresses to infection.7,10-12 Until recent research uncovered the Achilles’ heel of biofilm, it all but escaped treatment for several reasons: biofilm is not visually detectable, it forms quickly (often within minutes to hours of injury, much sooner than first believed), is hidden by inflammation in its initial stages and has been thought to involve free-floating bacteria, which are easily displaced by debridement or killed with topical treatments. These beliefs have fixated care options on free-floating bacteria, which addresses only a small part of the bacterial problem and causes treatment hesitation, thus allowing biofilm to proliferate and for pronounced infection symptoms to develop. Delayed attention or ineffective treatment nurtures biofilm, facilitating its spread even during bacterial eradication modalities and treatments that involve clinic-based debridement, dressings, antiseptics, and antibiotics.5-7,10-12 Convinced we have used all of the tools in our treatment toolbox, we watch and wait.

Fundamental wound care has not changed. Like the ABCs of cardiopulmonary resuscitation, we know what steps to follow, but we feel the need to jump from one treatment option to another when wounds fail to progress. Knowing that one of the top 3 reasons a wound fails to heal is infection, it may be time to reexamine our steps and reassess the evidence. Wound care science changes quickly; as such, it may be easy to confound the problem of nonhealing wounds by overlooking a source cause of not healing, sacrificing what new evidence is trying to tell us (ie, biofilm is everywhere). Awareness and acceptance of the need for infection prevention and definitive biofilm treatment has not kept pace with emerging evidence. As clinicians look for solutions, a slimy invisible biofilm may be sneakily contributing to the true nidus of many nonhealing wounds. If products and procedures such as outpatient debridement aren’t working, it’s time to reevaluate. Looking at wounds that refuse to heal through the lens that the failure to heal may be rooted in biofilm will provide a way to see nonhealing wounds in a new light. There are many reasons why wounds do not to heal; a biofilm-based infection should not be one of them.

Disclosure

Dr. Edens is Chief of Dermatology, Langley Dermatology Clinic, Hampton, VA. Ms. Stevenson is a clinical consultant, Next Science, Jacksonville, FL. The opinions and statements expressed herein are specific to the respective authors and not necessarily those of Wound Management & Prevention or HMP. This article was not subject to the Wound Management & Prevention peer-review process.

References

1.       Lazzarini PA, Pacella RE, Armstrong DG, van Netten JJ. Diabetes-related lower-extremity complications are a leading cause of the global burden of disability [published online May 23, 2018]. Diabet Med. 2018. doi: 10.1111/dme.13680.

2.      GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study [published correction appears in Lancet. 2017;390(10106):e38]. Lancet. 2016;390(10100):1211–1259.

3.      Skrepnek GH, Mills JL Sr, Lavery LA, Armstrong DG. Health care service and outcomes among an estimated 6.7 million ambulatory care diabetic foot cases in the U.S. Diabetes Care. 2017;40(7):936–942.

4.      Paisey RB, Abbott A, Levenson R, et al; South-West Cardiovascular Strategic Clinical Network Peer Diabetic Foot Service Review Team. Diabetes-related major lower limb amputation incidence is strongly related to diabetic foot service provision and improves with enhancement of services: peer review of the South-West of England. Diabet Med. 2018;35(1):53–62.

5.      Shadia M. Bacterial biofilm: dispersal and inhibition strategies. SAJ Biotechnol. 2014;1(105). doi: 10.18875/2375-6713.1.105.

6.      Petrova O, Sauer K. Sticky situations: key components that control bacterial surface attachment. J Bacteriol. 2012;194(10):2413–2425. 

7.      Lebeaux DC. From in vitro to in vivo models of bacterial biofilm-related infections. Pathogens. 2013;2(2):288–356.

8.      Elghblawi E. What Caused These Leg Ulcers? The Dermatologist. Available at: www.the-dermatologist.com/article/8336. Published September 4, 2008.  Accessed December 9, 2018. 

9.      Grimes C. Biofioms Cause Havoc for Breast Implants. The Plastic Surgery Channel. Available at: www.theplasticsurgerychannelcom/biofilms-cause-havoc-for-breast-implants. Published September 21, 2012. Accessed December 2, 2018.

10.    Hübner NO, Kramer A. Review on the efficacy, safety and clinical applications of polihexanide, a modern wound antiseptic. Skin Pharmacol Physiol. 2010;23(suppl):17–27. 

11.     Carpenter SD. Expert recommendations for optimizing outcomes in the management of biofilm to promote healing of chronic wounds. Wounds. 2016:28(6 suppl):S1–S20. 

12.    Kim PJ, Attinger CE, Bigham T, et al. Clinic-based debridement of chronic ulcers has minimal impact of bacteria. Wounds. 2018;30(5):114–119.

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