Clinical Assessment of a Biofilm-Disrupting Agent for the Management of Chronic Wounds Compared With Standard of Care

A Therapeutic Approach

Daniel Kim, MD; William Namen II, DPM; January Moore, BA; Mauricia Buchanan, BSN; Valerie Hayes, PhD; Matthew F. Myntti, PhD; Albert Hakaim, MD

Disclosures

Wounds. 2018;30(5):120-130. 

In This Article

Abstract and Introduction

Abstract

Objective. The authors study the use of a biofilm-disrupting wound gel designed for wound management to determine if disrupting chronic wound biofilm would be therapeutically efficacious.

Materials and Methods. This prospective, randomized, open-label clinical trial was performed from September 2014 through March 2016. Forty-three patients (22 experimental, 21 control) with chronic, recalcitrant wounds were randomized to a 12-week treatment with a biofilm-disrupting wound gel (experimental) or a broad-spectrum antimicrobial ointment (control). The wound healing rate was assessed by measuring wound size reduction and wound closure rates.

Results. Wound size in the experimental group decreased significantly with a 71% reduction in wound area compared with 24% for the control (P < .001). Wound closure was attained in more than half of the patients (14) treated with the experimental product. Fifty-three percent of these patients achieved closure by 12 weeks as opposed to 17% for the control (P < .01). No adverse events related to the experimental product were recorded, but 2 adverse reactions occurred with the control.

Conclusions. The combination of the experimental product and wound debridement significantly improved wound healing rates by disrupting the biofilm, which protects multispecies bacteria within a chronic wound. Given the significant wound size reduction and closure rates observed in these long-term, nonhealing wounds, as well as the lack of related serious adverse events, the investigators believe the biofilm-disrupting wound gel to be a safe and effective treatment for recalcitrant chronic wounds.

Introduction

Although the definition of a chronic wound varies, authors consider a wound chronic when it fails to proceed through an orderly reparative healing process that produces an anatomic and functional result within 1 to 3 months (as defined in surgical textbooks).[1] All wounds have the potential to become chronic, with the most common etiologies being venous insufficiency, arterial perfusion, diabetes, or unrelieved pressure.[2]

As health care costs continue to increase and conditions causing chronic wounds become more prevalent, it is necessary to find an efficacious yet cost-effective treatment for these nonhealing wounds.[3] Chronic wound care has been estimated to cost in excess of $25 billion per year, with a median cost of $3927 per wound.[4,5] Traditionally, a multidisciplinary treatment strategy is employed with the aim of correcting the underlying cause of the chronic wound; physical debridement, topical therapies, and dressings are in the armamentarium of chronic wound treatment.[6–10]

The presence of biofilms in chronic wounds presents significant obstacles to treatment, and it is estimated that biofilms are involved in more than 60% of patients with chronic wound infections.[10–12] Biofilms form when bacteria attach to a surface and aggregate to create a structure of extracellular polymeric substances (EPS) that protects bacteria and allows growth in a sheltered environment.[11,13] Biofilms can grow on a variety of surfaces, from medical devices to living tissue, and they are inherently resistant to antimicrobial agents.[14] The biofilm's resistance to antimicrobial agents occurs through multiple mechanisms, including physical protection from agents entering the biofilm, reaction of the agents with the EPS matrix (which may prevent deep penetration), or low metabolic activity of cells within the biofilm.[15,16] This resistance persists even with biofilm bacterial cells located at the surface of the biofilm, which would be expected to behave more like single-celled planktonic bacterial cells.[11] Ammons et al[10] investigated biofilms in chronic versus acute wounds and suggested that disruption of the biofilm aids in healing of chronic wounds.

Debridement is a mainstay of treatment for wound care. Sharp debridement removes nonviable tissue along with the bacterial biofilm, making the underlying bacterial load more susceptible to targeted therapy.[2,7] Wolcott and Rhoads[11] assessed biofilm-based treatment strategies, such as application of lactoferrin and xylitol with selective biocides, in combination with standard of care treatment. They showed a 75% healing frequency of chronic wounds in patients with diabetes and critical limb ischemia.[11] Wolcott[8] further showed that biofilm-based strategies, biofilm-disrupting agents, and application of antibiotic topical gels customized to each bacterial biofilm community in a specific wound resulted in over 40% chronic wound volume reduction over 4 weeks.

Surfactants are of interest in regard to autolytic debridement of chronic wounds. Miller et al[17] found that surfactants emulsified the biofilm matrix of Pseudomonas aeruginosa, and they also showed an elimination of biofilm bacteria 1 day after physical wiping and application of the surfactant gel to an ex vivo model.

In this study, the biofilm-disrupting wound gel is a polyethylene glycol-based hydrogel with a pH buffer system and benzalkonium chloride surfactant, which destabilizes the biofilm matrix through the chelation of calcium and removes proteins from bacterial membranes, causing cell lysis.[17] It is a white, virtually odorless gel that helps maintain a moist wound environment conducive to healing while eradicating biofilm from the surface of the wound. This biofilm-disrupting wound gel has been approved by the US Food and Drug Administration as a medical device; with full ISO 10993 safety testing, it was proven safe in a full-thickness porcine wound, whereby it had no negative effects on healing. The efficacy of this product has been demonstrated in in vivo[17] and in vitro models (data on file). In vitro biofilm testing was performed at the Montana State University Center for Biofilm Engineering (Bozeman, MT) in a mixed-species biofilm model, whereby the gel achieved more than a 3-log reduction in P aeruginosa and a 5-log reduction in Staphylococcus aureus in 24 hours (data on file). Miller et al[17] reported the efficacy of this product in clearing biofilms from murine models with chronic infections, which demonstrated the efficacy of this product in vivo.

Wolcott[8] conducted the first clinical study using this biofilm-disrupting gel and showed a 62% chronic wound volume reduction in 4 weeks (when applied 3x/week), while a combined application of both customized topical antibiotics and the wound gel resulted in a 72% wound volume reduction. In his 45-patient study, 80% of patients achieved at least 50% wound volume healing success within 1 month with the biofilm-disrupting wound gel alone.[8]

The present longer term clinical study is the second investigation of the efficacy of the biofilm-disrupting wound gel in the treatment of nonhealing, full-thickness chronic wounds to confirm the potential therapeutic effectiveness of this approach; this is achieved by measuring changes in the healing rate and wound closure when compared with a broad-spectrum, maximum-strength, triple antibiotic ointment over a 3-month time period.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....