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Journal Article

Development of a next-generation antimicrobial wound dressing.

TL;DR: The dressing was shown to effectively manage exudate and suspected biofilm while shifting difficult-to-heal wounds onto healing trajectories, after an average of 4 weeks of new dressing use in otherwise standard wound care protocols, accompanied by a low frequency of dressing related adverse events.
Abstract: Delayed wound healing due to infection is a burden on healthcare systems, and the patient and caregiver alike. An emerging factor in infection and delayed healing is the presence development of biofilm in wounds. Biofilm is communities of microorganisms, protected by an extracellular matrix of slime in the wound, which can tolerate host defences and applied antimicrobials such as antibiotics or antimicrobial dressings. A growing evidence base exists suggesting that biofilm exists in a majority of chronic wounds, and can be a precursor to infection while causing delayed healing itself. In vivo models have demonstrated that the inflammatory, granulation and epithelialization processes of normal wound healing are impaired by biofilm presence. The challenge in the development of a new antimicrobial wound dressing was to make standard antimicrobial agents more effective against biofilm, and this was answered following extensive biofilm research and testing. A combination of metal chelator, surfactant and pH control displayed highly synergistic anti-biofilm action with 1.2% ionic silver in a carboxymethylcellulose dressing. Its effectiveness was challenged and proven in complex in vitro and in vivo wound biofilm models, followed by clinical safety and performance demonstrations in a 42-patient study and 113 clinical evaluations. Post-market surveillance was conducted on the commercially available dressing, and in a 112-case evaluation, the dressing was shown to effectively manage exudate and suspected biofilm while shifting difficult-to-heal wounds onto healing trajectories, after an average of 4 weeks of new dressing use in otherwise standard wound care protocols. This was accompanied by a low frequency of dressing related adverse events. In a second evaluation, clinical signs of infection and wound dimension data, before and after the evaluations, were also available. Following an average of 5.4 weeks of dressing use, all signs of clinical infection were reduced, from an average frequency of 36% to 21%. An average of 62% wound size reduction was achieved, with 90% of wounds reducing in size and 10 wounds healing completely. The new clinical evidence for this next-generation antimicrobial wound dressing suggests it is safe and effective at managing exudate, infection and biofilm, while it can shift established, stubborn wounds onto healing trajectories. The scientific rationale for this new dressing technology is supported by in vitro and in vivo evidence, so now further comparative, randomized and outcome-based clinical studies are required to fully understand the clinical and economic benefits this new dressing technology can bring.

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Citations
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Journal ArticleDOI
TL;DR: In this narrative review, current and emerging non-antibiotic antimicrobial strategies will be considered and the need for antimicrobial stewardship in wound care will be explained.
Abstract: Control of wound infection today relies largely on antibiotics, but the continual emergence of antibiotic-resistant microorganisms threatens a return to the pre-antibiotic era when physicians used antiseptics to prevent and manage infection. Some of those antiseptics are still used today, and others have become available. A diverse variety of non-antibiotic antimicrobial interventions are found on modern formularies. Unlike the mode of action of antibiotics, which affect specific cellular target sites of pathogens, many non-antibiotic antimicrobials affect multiple cellular target sites in a non-specific way. Although this reduces the likelihood of selecting for resistant strains of microorganisms, some have emerged and cross-resistance between antibiotics and antiseptics has been detected. With the prospect of a post-antibiotic era looming, ways to maintain and extend our antimicrobial armamentarium must be found. In this narrative review, current and emerging non-antibiotic antimicrobial strategies will...

27 citations

Journal ArticleDOI
TL;DR: The effect of clinically used surfactants on biofilms will be discussed, with emphasis on poloxamer‐based surfactant, and the potential mechanisms behind the enhancement of wound healing and comparison to other surfACTants used in wound care are uncovered.
Abstract: Surfactants are widely used as detergents, emulsifiers, wetting agents, foaming agents, and dispersants in both the food and oil industry. Their use in a clinical setting is also common, particularly in wound care. Complicated or chronic wounds show clinical signs of delayed healing, persistent inflammation, and the production of non-viable tissue. These types of wounds also present challenges such as infection and potentially house antimicrobial-tolerant biofilms. The use of wound cleansers to aid cleaning and debridement of the wound is essential. A large proportion of skin and wound cleansers contain surfactants but there is only a small amount of data that shows the effectiveness of them in the enhancement of wound closure. This review paper aims to explore the available literature surrounding the use and mode of action of surfactants in wound healing, in particular Poloxamer 188 (Pluronic F-68) and Poloxamer 407 (Pluronic F-127), and also uncover the potential mechanisms behind the enhancement of wound healing and comparison to other surfactants used in wound care. Furthermore, the presence of a microbial biofilm in the wound is a significant factor in delayed wound healing. Therefore, the effect of clinically used surfactants on biofilms will be discussed, with emphasis on poloxamer-based surfactants.

27 citations


Additional excerpts

  • ...This combination was effective against biofilm and reduced the signs of clinical infection in a 42-patient study.(37) Research into the cosmetic use of biosurfactants is developing due to their cleansing, emulsifying, foaming and skin hydrating properties....

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Journal Article
TL;DR: In this article, the authors collate knowledge and evidence of the visual and indirect clinical indicators of wound biofilm, and propose an algorithm designed to facilitate clinical recognition of biofilm and subsequent wound management practices.
Abstract: Recognition of the existence of biofilm in chronic wounds is increasing among wound care practitioners, and a growing body of evidence indicates that biofilm contributes significantly to wound recalcitrance. While clinical guidelines regarding the involvement of biofilm in human bacterial infections have been proposed, there remains uncertainty and lack of guidance towards biofilm presence in wounds. The intention of this report is to collate knowledge and evidence of the visual and indirect clinical indicators of wound biofilm, and propose an algorithm designed to facilitate clinical recognition of biofilm and subsequent wound management practices.

16 citations

Journal Article
TL;DR: The investigators believe the biofilm-disrupting wound gel to be a safe and effective treatment for recalcitrant chronic wounds due to the significant wound size reduction and closure rates observed in these long-term, nonhealing wounds.
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.

13 citations

Journal ArticleDOI
TL;DR: It is demonstrated that a concentrated surfactant gel preserved with antimicrobials is non‐cytotoxic and has ability to accelerate wound closure by enhancing cell mobility and helping to retain the plasma membrane integrity and enhanced wound healing.
Abstract: In this study, three cellular cytotoxic assays (direct contact assay, extraction assay, and cell insert assay) were applied to evaluate the effects of a concentrated surfactant gel preserved with antimicrobials and a concentrated surfactant gel with 1% silver sulfadiazine on both the mouse fibroblast cell line L929 and human dermal fibroblasts (HDFa). Also, the in vitro wound model was wounded by a 100 μL pipette tip and used to assess cell migration and wound closure after treatment with both gels. A needle-scratched membrane disruption model was used to preliminarily evaluate membrane stabilisation and the membrane-resealing effects of concentrated surfactant gels. It was demonstrated that the concentrated surfactant gel preserved with antimicrobials was not toxic to both L929 and HDFa. However, the concentrated surfactant gel with 1% silver sulfadiazine demonstrated a degree of cytotoxicity to both cell types. After treatment with a concentrated surfactant gel preserved with antimicrobials, cell movement to close the scratch gap was enhanced at 24 and 48 hours. The results also showed that cells treated with the concentrated surfactant gel preserved with antimicrobials decreased cell necrosis and improved cell resistance of the f-actin rearrangement after a needle scratch. The results demonstrated that a concentrated surfactant gel preserved with antimicrobials is non-cytotoxic and has ability to accelerate wound closure by enhancing cell mobility. Furthermore, the concentrated surfactant gel appeared to stabilise the plasma membrane and demonstrated a resealing ability and helped to retain the plasma membrane integrity and enhanced wound healing.

7 citations

References
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Journal ArticleDOI
TL;DR: Owing to the heterogeneous nature of the biofilm, it is likely that there are multiple resistance mechanisms at work within a single community.

3,578 citations


"Development of a next-generation an..." refers background in this paper

  • ...At this stage the bioi lm will be microscopic but may start to illicit an inl ammatory host response, and if unchecked, can develop into larger, more elaborate communities (16)....

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Journal ArticleDOI
TL;DR: The results reviewed in this article indicate that the formation of biofilms serves as a new model system for the study of microbial development.
Abstract: ▪ Abstract Biofilms can be defined as communities of microorganisms attached to a surface. It is clear that microorganisms undergo profound changes during their transition from planktonic (free-swimming) organisms to cells that are part of a complex, surface-attached community. These changes are reflected in the new phenotypic characteristics developed by biofilm bacteria and occur in response to a variety of environmental signals. Recent genetic and molecular approaches used to study bacterial and fungal biofilms have identified genes and regulatory circuits important for initial cell-surface interactions, biofilm maturation, and the return of biofilm microorganisms to a planktonic mode of growth. Studies to date suggest that the planktonic-biofilm transition is a complex and highly regulated process. The results reviewed in this article indicate that the formation of biofilms serves as a new model system for the study of microbial development.

3,321 citations


"Development of a next-generation an..." refers background in this paper

  • ...Established wound bioi lm therefore presents a serious infection risk, and may also seed bioi lm formation elsewhere in the wound (19)....

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Journal ArticleDOI
TL;DR: Although exopolysaccharides provide the matrix framework, a wide range of enzyme activities can be found within the biofilm, some of which will greatly affect structural integrity and stability.

1,203 citations


"Development of a next-generation an..." refers background in this paper

  • ...Knowing that the complex three-dimensional matrix of EPS was generally comprised of hydrated polysaccharides, protein and DNA of microbial origin, as well as host-derived devitalised tissues (12,35), the search for safe and ef ective means by which to target this matrix was undertaken....

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Journal ArticleDOI
TL;DR: An appreciation of the factors affecting the progression from colonization to infection can help clinicians with the interpretation of clinical findings and microbiological investigations in patients with chronic wounds.
Abstract: Purpose of reviewWound healing is a complex process with many potential factors that can delay healing. There is increasing interest in the effects of bacteria on the processes of wound healing. All chronic wounds are colonized by bacteria, with low levels of bacteria being beneficial to the wound h

896 citations


"Development of a next-generation an..." refers background in this paper

  • ...As a result, bioi lm microorganisms can display tolerance towards systemic antibiotics and topically-applied antiseptics, such as silver or iodine (14), as well as host defence mechanisms, such as phagocytosis and enzyme-mediated microbial killing by neutrophils (15)....

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Journal ArticleDOI
TL;DR: It is proposed that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF).
Abstract: The present paper presents a hypothesis aimed at explaining why venous leg ulcers, pressure ulcers, and diabetic foot ulcers develop into a chronic state. We propose that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF). We have analyzed sections from chronic wounds by fluorescence in situ hybridization and found distinct microcolonies--the basal structures of bacterial biofilms. Several researchers have previously reported that another important hallmark of biofilm formation is development of increased tolerance to various antimicrobial measures and treatments. Furthermore, the immune response to infecting bacteria in the cystic fibrosis lung is dominated by polymorphonuclear neutrophils (PMNs), and we have recently shown that in vitro biofilms of P. aeruginosa produce a shielding mechanism that offers protection from the phagocytic activity of PMNs. We hypothesize that the presence of P. aeruginosa in biofilms, and the lack of concomitant elimination by attended PMNs, are the main causes of inefficient eradication by antibiotic treatment and antimicrobial activity of the innate immune system, respectively.

786 citations


"Development of a next-generation an..." refers background in this paper

  • ...As a result, bioi lm microorganisms can display tolerance towards systemic antibiotics and topically-applied antiseptics, such as silver or iodine (14), as well as host defence mechanisms, such as phagocytosis and enzyme-mediated microbial killing by neutrophils (15)....

    [...]