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

Discussion

This study confirms that topical applications of a biofilm-disrupting wound gel in conjunction with debridements produce clinically significant wound size reductions and wound closure versus a broad-spectrum topical antibiotic treatment control. In this study, median wound area reduction was 72% with daily use of the experimental product for 12 weeks versus 24% with the control. Chronic wound closure occurred in 53% of patients with the use of the experimental product versus 17% closure with the control.[8] These results reinforce those obtained by Wolcott,[8] who observed a wound volume reduction of 62% with the biofilm-disrupting wound gel applied 3 times per week for 4 weeks. Notably, Wolcott[8] achieved the 47% wound volume reduction with standard of care treatment versus 24% wound area reduction seen with the control treatment in this study. It is important to note that in that clinical study, Wolcott's standard of care treatment was a proprietary topical antibiotic gel customized and compounded based on each patient's identified biofilm bacterial community.[8]

The control treatment used in this study was a maximum-strength, widely available, triple-antibiotic ointment that targets common bacteria found in chronic wounds;[18,19] per 1 gram, the ointment contains 500 units of bacitracin, 3.5 mg of neomycin, 10 000 units of polymyxin B, and 10 mg of pramoxine hydrochloride. This product was chosen as the control treatment because it is a comparable antimicrobial agent with similar indication to the experimental wound gel with the broadest spectrum of activity versus bacitracin or other single-species-specific antibiotic ointments. The triple-antibiotic components aim at medically significant species implied in skin infections, such as S aureus, S epidermis, and Streptococcus pyogenes. This also includes polymyxin B specific to gram-negative species such as P aeruginosa and neomycin, which has a partial efficacy spectrum on gram-positive bacteria, Enterobacter cloacae, E coli, and Proteus vulgaris in addition to gram-negative species activity. Furthermore, broad-spectrum topical antibiotics are used in chronic wounds to provide a high concentration of medication directly to the wound site and to avoid systemic disturbance of the normal microbiota as well as systemic allergic reactions.[18] Prior to this study, patients were treated with various therapies, including oral and topical antibiotics, antimicrobial dressings, silver alginate, and wound vacuum devices that had all failed to resolve the chronicity of their wounds.

In this study, biofilm data analysis showed that neither wound size reduction nor wound closure was significantly affected by total bacterial load or number of bacterial species. However, it has been shown that the number of individual bacteria is not considered a reliable predictor of wound healing, as numbers will change based on virulence of the bacteria, biofilm formation, and comorbidities.[20] In addition, antagonistic and synergistic interactions of bacterial species within the biofilm can result in changes in its makeup, which also was observed in this study.[21] Further study into the change in specific bacterial loads after application of the experimental wound gel may be helpful to better understand the wound gel's effects on the biofilm.

In the literature on chronic wound management, there is a lack of prospective, randomized, controlled clinical studies, which makes it challenging for practitioners to compare the efficacy of topical products currently available. Also, articles seldom provide analysis of clinically meaningful wound healing rates and closure; in most cases, the percent wound size reduction is provided as a measure of efficacy, which alone is only a partial indication of wound improvement. This leaves a desire for clinically meaningful wound healing, as the goal is for wounds to heal and remain healed. Further, biofilm-disputing technology is new and most topical treatments are antibiotic-based with narrow spectrum of efficacy.

In addition, biofilm testing methods with clinical relevance to practitioners are lacking. To the best of the authors' knowledge, there are 3 methods that could be used for product efficacy comparison, but all 3 are time-consuming to perform and reporting is too delayed for them to be used in routine practice. Montana State University has developed an in vitro biofilm model where mixed-species colonies of P aeruginosa and S aureus are grown in a chronic wound with exudate-like environment.[22] This drip-flow biofilm model can be used to test a product's efficacy against gram-positive and gram-negative bacteria, and it provides a measurement of log reduction of both biofilm species.[23] The University of Florida (UF; Gainesville, FL) also has developed a test method that detects and quantifies several viable biofilm microorganisms through a series of targeted specimen washes and selection by differential growth media.[24,25] This method could compare product efficacy as it provides the type and the amount of viable microorganisms present in patient specimens.[24,25] The third method available is the molecular analysis method described earlier in this clinical study, which was developed by Wolcott.[8]

All 3 of the aforementioned methods have limitations. For instance, the MSU and the UF methods are limited in the number of viable species of biofilm microorganisms that can be analyzed, and these are not available as large-scale clinical diagnostic tests. The molecular analysis is available as a clinical tool that provides qualitative and quantitative results on innumerable bacterial and fungal species but does not differentiate live from dead or pathogenic from nonpathogenic microorganisms.[26] However, results from the molecular analysis are reliable, and high representation of 1 or more species in a patient specimen is unlikely to originate from nonviable microorganisms. This molecular method has been shown to be clinically relevant in improving the diagnostic and treatment outcomes of patients with chronic wounds[6] as well as actionable diagnosis where conventional diagnostic work-up is unrevealing.[23,27]

A comparison of the available antibiofilm wound products' clinical data shows that the experimental agent results in the highest percentages of healed wounds and wound size reduction available to date (Table 7[8,28,30,33]). Although this product was evaluated under more stringent randomized controlled study conditions compared with the retrospective record reviews of other similar products, the average wound closure rates with the experimental agent was greater than AQUACEL Ag Extra (ConvaTec, Deeside, Flintshire, UK). Compared to Prontosan Wound Irrigation Solution and Gel (B. Braun Medical Inc, Bethlehem, PA) products, treatment of chronic wounds with the experimental agent in this study resulted in substantially more healed wounds and a higher percentage of improved wounds (Table 7[8,28,30,33]). While iodine-based topical products have been commercialized for more than 170 years,[29] efficacy data against biofilm is based on limited clinical evidence.[28,30] When comparing the results of a prospective, randomized controlled study by Hansson[28] with the experimental product in the present study at 12 weeks of treatment, IODOSORB (Smith & Nephew, Hull, UK) showed a 62% average wound closure rate and the experimental agent showed 71%.

Another important aspect for the practitioner is the patient's tolerance to wound care treatment. The use of the experimental agent did not result in any product-related pain, redness, swelling, burning/stinging, or other adverse reactions in the 34 patients in this study. This is in line with the observations of the Wolcott clinical study[8] where 30 patients were treated with the same biofilm-disrupting agent.

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