In my recent WoundSource webinar on the assessment and treatment of chronic wounds and biofilms, I discussed the pathogenesis of chronic wounds and offered a biofilm-based wound care protocol to promote healing. The webinar covered the following topics:

• The prevalence of biofilms in chronic skin wounds
• The mechanism of action of biofilm in the wound bed and how this impairs wound healing
• The concept of Biofilm-Based Wound Care
• Use of effective local antimicrobial treatments to prevent biofilm reformation
• The Step-Down-Then-Step-Up approach for effective therapies for chronic wounds

The following are frequently asked questions and my answers.

Frequently Asked Questions about Chronic Wounds and Biofilms

Question: Is the biofilm-based wound care step-down-then-step-up approach universally useful for all chronic wounds regardless of etiology?

Answer: Yes. Chronic wounds have a high probability of a common molecular pathology pathway involving biofilms that create elevated proteases and reactive oxygen species (ROS) that prevent wound healing. ROS is an important factor that is elevated in chronic inflammation and can impair healing by oxidative degrading proteins and lipid molecules that are essential for healing. The step-down-then-step-up approach aims to streamline all the multiple treatment and dressing modalities into a comprehensive, simplified, general approach. The first step is effective debridement. Because almost all chronic wounds will have biofilm, the next step is to use topical treatments that will reduce the remaining planktonic bacteria and biofilm to a level where the wound can start healing. At that point, wound healing can be accelerated with the use of advanced wound care products. To summarize, the step-down component of the approach reduces the biofilm and bioburden, and the step-up portion begins when the wound bed is prepared and ready for advanced treatments.

Question: Do any biophysical treatments, such as ultrasound or electrostimulation, affect biofilm?

Answer: Yes. The literature contains reports on the efficacy of both ultrasound and electrostimulation in wound healing. Ultrasound¹ has been found to reduce planktonic bacteria and biofilms in chronic wounds. The key is to use a microbicidal solution to deliver the ultrasound energy. In a recent report on the use of electrostimulation,² a dressing that generated an electric field was applied to wounds and improved healing. However, electrostimulation remains controversial because the commercially available dressings that generate an electrical field are relatively new to the market.

Question: What is an effective treatment approach when managing a chronic wound with Pseudomonas infection and without systemic infection?

Answer: The step-down-then-step-up approach is the general treatment strategy recommended. Because Pseudomonas creates such a robust biofilm, the key to treating wounds infected with this organism is to debride the wound as aggressively as possible initially and then apply a topical antimicrobial. Studies have shown that the most effective topical antimicrobial to combine with the debridement for these wounds is cadexomer iodine.³

Question: Should negative pressure wound therapy using the instill feature be used on a wound biofilm, and if so, what solution should be considered for use?

Answer: Negative pressure wound therapy with instillation is much more effective at reducing biofilms than negative pressure therapy alone. Several approved wound wash solutions can be used for instillation. Examples include Protosan wound irrigation solution, diluted chlorhexidine, and very dilute iodide solutions. Studies of negative pressure plus instillation have been published.⁴ One report describes the use of saline instillation after thorough wound debridement. The instill feature is optimal for initial treatments of wounds that have a very high bioburden, are infected, and have biofilms. Initially it is best to use a microbicidal wound wash solution. Then as the wounds began to heal and the bioburden is reduced, the instillation solution can be stepped down to saline. Even here, the step-down-then-step up approach works.

Want to learn more about chronic wounds and biofilms? Watch the webinar here.

Question: How can you identify in a test analysis that a biofilm is present and is not planktonic bacteria or infection?

Answer: Standard clinical microbiology laboratories detect planktonic bacteria, but no test specifically for biofilms is available to clinicians. Although a test analysis to detect a biofilm does exist, it is generally restricted to research laboratories. Standard test results show planktonic bacteria, and only about 20% of all the bacteria species that are present actually are cultured because the others do not grow well on culture plates. However, some good surrogate indicators of biofilms do exist and are useful, including the presence of significant amounts of exudate and slough and a wound area of non-healing when the other parts of the wound appear to be healing well.

Question: Can you address the issue of topical antimicrobial use and the idea that wounds should not be treated with these agents unless wounds are clinically infected?

Answer: Current U.S. and European guidelines for antimicrobial stewardship caution against overuse or inappropriate use of topical or systemic antibiotics, to avoid the increase of antibiotic-resistant organisms. These guidelines are especially appropriate for chronic wounds because antibiotics have a minimal effect on biofilms. Another issue is the important distinction between antibiotics and general antimicrobials. Many pathogens have developed genetic resistance to antibiotics, but very few have developed genetic resistance to general antimicrobials.

The best approach is to use a topical non-antibiotic antimicrobial dressing approved by the FDA as a bacterial barrier that prevents bacteria from passing through the dressing to the wound bed and also prevents growth of bacteria in the dressing. This type of dressing inhibits organisms that come in contact with the dressing, rather than releasing antimicrobial materials such as polyhexamethylene biguanide or iodine into the wound bed. Topical antimicrobials such as cadexomer iodine ointments are designed to treat infected wounds, and the other dressings are intended to block bacteria and prevent bacterial growth in the dressings. Once the pathogens in the wound bed are under control, you can step down to just an antimicrobial dressing or just a barrier dressing.

Question: Some studies suggest that wiping decreases biofilm presence. Is this considered standard wound care, and should a specific method be used for wound care between clinic visits?

Answer: It is certainly part of standard of wound care to wipe and cleanse the wound bed with antimicrobial-containing gauze or microfiber pads. However, these materials decrease, but do not remove, all of the biofilm because much of the biofilm is under the surface of the wound bed and must be debrided if at all possible.

That said, several of the larger wound care companies are coming out with dressings that are more effective at removing slough and superficial biofilm.⁵ As for whether a specific method should be used for wound care between clinic visits, patients who remove and reapply their wound dressings between visits should be given materials or instructed on how to cleanse the wound bed between or during dressing changes. These patients should also be taught the difference between simply rinsing, irrigating, or anointing the wound bed and effectively cleansing and wiping it. It takes more than rinsing to remove biofilm.

Question: Does nutritional intake, such as protein, play a role in biofilm formation?

Answer: No, because biofilm formation occurs in both nutritionally deficient and nutritionally competent patients. Most patients are not nutritionally deficient, so the materials used by planktonic bacteria to grow are already present in the wound bed. Most of the time, the bacteria in a chronic wound are not stressed metabolically because they have food available from the wound fluid from the plasma exudate, and they break down the matrix of the wound bed through their proteases. These bacteria use a quorum sensing system to help in biofilm formation, as noted in laboratory studies.⁶ Therefore, the patient’s nutritional intake is probably not a dominant factor in stimulating biofilm formation. More relevant is the actual density of the bacteria in the wound bed.

References

1. Braumann C., L ázaro-Martínez J., Schultz G., Swanson T. Söring UAW made easy. Wounds International. 2017.

2. Alhede M., Bjarnshot T., Crone S., Garde C. A novel in vitro wound biofilm model used to evaluate low-frequency ultrasonic-assisted wound debridement. Journal of wound care. 2015; 24(2).

3. Azeke J., Davis S., Hamad A., Phillips P., Sampson E., Schultz G., Yang Q. Antimicrobial dressing efficacy against mature Pseudomonas aeruginosa biofilm on porcine skin explants. International Wound Journal. 2013.

4. Phillips P., Schultz G., Yang Q. The effect of negatie pressure wound therapy with periodic instillation using antimicrobial solutions on Pseudomonas aerginosa biofilm on porcine skin explants. International Wound Journal. 2013.

5. Schultz G., Weir D., Woo K., Yang Q. Effectiveness of a monofilament wound debridement pad at removing biofilm and slough: ex vivo and clinical performance. Journal of Wound Care. 2018; 27(2).

6. Balaban N., Cirioni o., Dell’Aqua G., Giacometti A., Ghiselli R., Gov Y., et al. Use of quorum-sensing inhibitor rnaiii-inhibiting pptide o prevent biofilm formation in vivo by drug-resistant staphylococcus epidermidis. JID. 2003; 187.

About the Author

Gregory Schultz, PhD, is Professor of Obstetrics and Gynecology and Director of the Institute for Wound Research at the University of Florida. A major area of his research focuses on defining the role of bacterial biofilms in stimulating chronic inflammation and proteases that impair healing in chronic wounds. Dr. Schultz has co-authored 400 scientific publications that have been cited over 17,000 times, has received $38 million grant support as Principal Investigator or Co-investigator, is an inventor on 31 patents, and is a co-founder of two biotech companies in the areas of antimicrobial coatings and antiscarring drugs. He served as President of the Wound Healing Society (1999-2001) and as a member of the National Pressure Ulcer Advisory Panel (2007-2010).