Why Reducing Biofilm Infections Is Essential to Any Wound Clinic’s Strategy

Due to the health care disruptions caused by COVID-19, wound clinics may be seeing stable wounds develop unstable infections. With biofilm at the core of many infected wounds, this author takes a look at promising treatments to combat biofilm and help heal chronic wounds.

COVID-19 and its initial intensity may be ebbing, but the aftermath of its impact is not over. Beginning early in 2020, responding to the increasing needs of patients with the coronavirus, the Centers for Medicare and Medicaid Services (CMS) recommended that providers postpone all but the most critical non-COVID patients who were scheduled for elective surgeries, along with non-essential medical, surgical, and dental procedures, meaning that open access to health care changed for a great number of patients.¹

Chronic wound care was included as a non-essential procedure. As one surgeon explained, “one of the key challenges during this time has been patients presenting late (either not wanting to see a clinician due to shielding, or not being able to get to their general practitioner for a referral), and often having deteriorated or developed limb-threatening complications or infection,” a description that still resonates today.²

Although most health care systems are up and running again, no one knows for how long. Wound care has taken on the feel of a MASH unit—the window of opportunity to address healing barriers becoming even more time dependent, compressed by the unknown of a possible pandemic flare up. The lingering pressure of a COVID resurgence is still in full force, causing a push to work though backlogged surgeries, quickly complete current surgical cases, and pack wound clinic schedules.

As medical priorities have continued to shift around the post-pandemic reopening, the resources of many hospitals and wound clinics have been stretched beyond capacity. Providers are seeing previously stable wounds develop into unstable infections in the background of COVID emergencies, the perfect opportunity for the growth of biofilm.

The Threat Biofilm Poses for Wounds

During a period when it is more important than ever to minimize time spent in the hospital, it is vital that any wound-care strategy be immediate, effective, and designed to reduce or alleviate possible wound deterioration from any source including biofilm-mediated recurring or progressive infections. In terms of threats, biofilm is one of the most prevalent risks for patients with wounds, especially those with diabetes whose wounds virtually all have biofilm.³ Biofilm has become a common theme in the provision of wound care with seemingly many remedies.

While most wound-care solutions target only free-floating planktonic bacteria, the number of bacterial infections that involve biofilms varies depending on the reporting agency. Estimates are that biofilm is involved in 65% of all infections according to the Centers for Disease Control and Prevention (CDC), and 80% according to the National Institutes of Health (NIH).^4,5 This contributes to approximately 550,000 American deaths (all-cause medical biofilm diseases) each year and with an estimated direct annual cost of $94 billion to treat.^4,5 In a large retrospective study of Medicare beneficiaries, nearly 15% had a chronic wound or infection during the course of a year.¹ The most common wounds are a result of diabetes, venous/arterial insufficiency, or pressure, which has made these patients particularly comorbid and at risk for death from inflammatory cytokine storms associated with the COVID-19 virus.^6,7 The shift in care due to COVID has become an obstacle to best practice in many circumstances.¹

The term “biofilm” is becoming a flash point in the medical industry as a biofilm is found at the core of most, if not all, chronic or recurring disease states, including hard-to-heal wounds. Whatever the wound-care setting, a key to expediting wound closure is to reduce the presence and further risk of biofilm-driven infection. Understanding the true science of biofilm is complex; however, without this knowledge, alleviating biofilm becomes reliant on scientifically confusing answers that prioritize eradication of the free-floating bacteria instead of elimination of the protective matrix that shields over 90% of the wound bacteria.⁸

Protected by the extracellular polymeric substance (EPS)—biofilm’s outer structure—and fed by the inflammatory process, biofilm becomes persistent, stalling wound healing processes and rendering traditional treatments ineffective.⁹ Furthermore, while simply disrupting the EPS biofilm shelter does expose some of the protected bacteria to bactericidal treatments, if the structure remains intact through the mechanical and chemical fragmenting found when oxidizing agents are used or with debridement, biofilm is rapidly reestablished in as little as 24 hours.¹⁰ The benefit of wound debridement, though, cannot be disregarded as it opens a time-dependent window before biofilm regrowth, especially when paired with effective targeted biofilm care.¹¹

A Closer Look at Solutions for Biofilm

Biotech companies are now developing wound-care solutions that target and destroy biofilm, not just planktonic bacteria, and the best of those solutions are broad spectrum and have a sustained effect, with no known antimicrobial resistance, and are non-toxic and gentle on the body.¹²

The most sophisticated biofilm-disruption solutions work by binding the strong metallic bonds that hold together a biofilm’s EPS, then capping the released polymers to prevent biofilm reformation, effectively bringing that EPS into solution so it cannot reorganize into a new protective structure. This action exposes the bacteria located within the biofilm, making them more vulnerable to attack by antimicrobials, antibiotics, and the body’s natural immune defenses. In doing so, it then also helps reduce the rate of biofilm recurrence by more than 100 times.¹⁴

Biofilm technology can be used in various products designed to prevent surgical-site and postoperative infections and resolve biofilms in chronic wounds. Those products include no-rinse antimicrobial solutions, surgical lavages, and sterile surgical wound gels. Of perhaps greatest interest to wound clinics, though, is antimicrobial wound gels that target biofilm and can be prescribed for in-home patient use to help manage wounds, such as diabetic foot ulcers and pressure ulcers.

BLASTX (Next Science) is synergistically powered by a patented non-toxic biofilm technology, XBIO. The effectiveness of BLASTX, also named Next Science Wound Gel, has demonstrated significantly higher efficacy than that of comparators in 2 clinical studies and in rigorous bench testing.^13,15-17 In a three-arm, randomized controlled trial in patients with recalcitrant chronic wounds, using the Food and Drug Administration (FDA)–defined surrogate of 50% reduction in wound volume at 1 month, results showed that a customized standard of care gel healed at 53%, BLASTX gel healed at 80% and use of the combination of the customized standard of care gel plus the BLASTX gel resulted in 93% of wounds successfully treated.¹⁵    

A second recently completed Mayo Clinic study found that over 12 weeks, patients using BLASTX saw the size of their wounds reduce 3 times more than study participants who used a standard wound-care product (P < 0.01).¹⁶ There were no adverse events related to the biofilm-disrupting BLASTX product while 2 adverse reactions occurred with the antibiotic control group. 

The difference is noticeable in the clinic and in the laboratory. According to a recent article in Wound Repair and Regeneration in March 2020, the authors stated, “There are several topical antimicrobial wound care products available for use; however, their effectiveness has routinely been demonstrated with planktonic microorganisms. In addition, data on antimicrobial activity of products in biofilm models is scattered across many test methods in a variety of studies.”¹⁷ Findings from this testing eye-opener identified that biofilm testing models are not all equal and fail to provide an apples-to-apples effectiveness standard, confuse the clinicians, and portray an effectiveness against biofilm that is misleading.

Dr. Matthew Regulski is the medical director of the Wound Care Institute of Ocean County, New Jersey. He is also a surgeon consultant for Next Science, a medical technology company whose proprietary XBIO Technology powers a range of medical devices to reduce the impact of biofilm-based infections in human health.

References

1. Rogers LC, Armstrong DG, Capotorto J, et al. Wound center without walls: the new model of providing care during the COVID-19 pandemic. Wounds. 2020; 32(7):178–185.

2. Chadwick PB, Bowen G, Hart S, et al. Learning from COVID-19: developing a more efficient podiatry service. Wounds International. https://www.woundsinternational.com/resources/details/learning-covid-19-developing-more-efficient-podiatry-service . Published Oct. 7, 2020.

3. Johani K, Malone M, Jensen S, Gosbell I, Dickson H, Hu H, Vickery K. Microscopy visualisation confirms multi-species biofilms are ubiquitous in diabetic foot ulcers. Int Wound J. 2017; 14(6):1160–69. doi: 10.1111/iwj.12777

4. Joo HS, Otto M. Molecular basis of in-vivo biofilm formation by bacterial. Chemistry Biol. 2012;19(12):1503-1513.

5. Wolcott RD, Rhoads DD, Bennett ME, et al. Chronic wounds and the medical biofilm paradigm. J Wound Care. 2010; 19(2):45–6, 48–50, 52–3.

6. Hojyo S, Uchida M, Tanaka K, et al. How COVID-19 induces cytokine storm with high mortality. Inflamm Regen. 2020; 40: 37. Epub Oct. 1. doi: 10.1186/s41232-020-00146-3 PMCID: PMC7527296

7. O’Neill J. Antimicrobial resistance: tackling a crisis for the health and wealth of nations. London, UK: Review on Antimicrobial Resistance. 2014 Accessed online: http://bit.ly/2PNPkHt

8. Petrova OS, Sauer K. Sticky situations: key components that control bacterial surface attachment. J Bacteriol. 2021; 194(10):2413–2425.

9. Regulski M, Stevenson P. Biofilm-hijacked inflammation: the missing link to hard-to-heal wounds. Wound Manage Prevent. 2019; 65(4):8–10.

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

11. Wolcott RD, Rumbaugh KP, James G, et al. Biofilm maturity studies indicate sharp debridement opens a time-dependent therapeutic window. J Wound Care. 2010; 19(8):320–8. doi:10.12968/jowc.2010.19.8.77709

12. Hübner NO, Kramer A. Review on the efficacy, safety and clinical applications of polyhexanide, a modern wound antiseptic. Skin Pharmacol Physiol. 2010;23(Suppl 1):17-27.

13. Laboratory data on file.

14. Esin L, Antonelli, PJ, Ojano-Dirain C. Effect of haemophilus influenza exposure on staphylococcus aureus tympanostomy tube attachment and biofilm formation. JAMA Otolaryngol Heal Neck Surg. 2015; 141(2):148–53.

15. Wolcott R. Disrupting the biofilm matrix improves wound healing outcomes. J Wound Care. 2015 Aug;24(8):366–71.

16. Kim D, Namen W, Moore J, Buchanan M. Clinical assessment of a biofilm-disrupting agent for the management of chronic wounds compared with standard of care: a therapeutic approach. Wounds. 2018; 30(5):120–30.

17. Stoffel J, Kohler Riedi PL, Romdhane BH. A multimodel regime for evaluating effectiveness of antimicrobial wound care products in microbial biofilms. Wound Rep Regen. 2020; 28(4):438–47.