Bacterial resistance to silver in wound care.

Dressings have a part to play in the management of wounds; whether they are sutured or open, usually chronic wounds of many aetiologies which are healing by secondary intention. They traditionally provide a moist wound environment, but this property has been extended through simple to complex, active dressings which can handle excessive exudate, aid in debridement, and promote disorganised, stalled healing. The control of infection remains a major challenge. Inappropriate antibiotic use risks allergy, toxicity and most importantly resistance, which is much reduced by the use of topical antiseptics (such as povidone iodine and chlorhexidine). The definition of what is an antimicrobial and the recognition of infection has proven difficult. Although silver has been recognised for centuries to inhibit infection its use in wound care is relatively recent. Evidence of the efficacy of the growing number of silver dressings in clinical trials, judged by the criteria of the Cochrane Collaboration, is lacking, but there are good indications for the use of silver dressings, to remove or reduce an increasing bioburden in burns and open wounds healing by secondary intention, or to act as a barrier against cross contamination of resistant organisms such as MRSA. More laboratory, and clinical data in particular, are needed to prove the value of the many silver dressings which are now available. Some confusion persists over the measurement of toxicity and antibacterial activity but all dressings provide an antibacterial action, involving several methods of delivery. Nanocrystalline technology appears to give the highest, sustained release of silver to a wound without clear risk of toxicity.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1742-481X.2006.00265.x

Silver dressings: their role in wound management.

Over the past decade, a variety of advanced silver-based dressings have been developed There are considerable variations in the structure, composition, and silver content of these new preparations In the present study, we examined five commercially available silver-based dressings (Acticoatt, Aquacel s Ag, Contreet s Foam, PolyMem s Silver, Urgotul s SSD) We assessed their cytotoxicity in a monolayer cell culture, a tissue explant culture model, and a mouse excisional wound model The results showed that Acticoatt, Aquacel s Ag, and Contreet s Foam, when pretreated with specific solutes, were likely to produce the most significant cytotoxic effects on both cultured keratinocytes and fibroblasts, while PolyMem s Silver and Urgotul s SSD demonstrated the least cytotoxicity The cytotoxicity correlated with the silver released from the dressings as measured by silver concentration in the culture medium In the tissue explant culture model, in which the epidermal cell proliferation was evaluated, all silver dressings resulted in a significant delay of reepithelialization In the mouse excisional wound model, Acticoatt and Contreet s Foam indicated a strong inhibition of wound reepithelialization on the postwounding-day 7 These findings may, in part, explain the clinical observations of delayed wound healing or inhibition of wound epithelialization after the use of certain topical silver dressings Caution should be exercised in using silverbased dressings in clean superficial wounds such as donor sites and superficial burns and also when cultured cells are being applied to wounds The use of silver as an antimicrobial agent has a long history 1 Its recent resurgence follows from Moyer’s use of silver nitrate solution in patients with burns 2 Solutions gave way to cream formulations but it is now silver-containing dressings that provide the widest range of silverbased wound care products 3,4 Despite the ever increasing number of commercially available silver-based dressings, there is a distinct lack of comparative data on their clinical effectiveness 5 What is known is that silver can be effective against a wide range of microorganisms, including aerobic, anaerobic, Gram-negative and Gram-positive bacteria, yeast, fungi, and viruses The antimicrobial effect of silver can be explained by various mechanisms: silver interferes with the respiratory chain in the cytochromes of microbacteria; additionally, silver ions also interfere with components of the microbial electron transport system, bind DNA, and inhibit DNA replication 6,7 Dressings are designed to have more controlled and prolonged release of silver during the entire wear-time when compared with the cream formulations This allows dressings to be changed less frequently, thereby reducing risk of nosocomial infection, cost of care, further tissue damage, and patient discomfort Many factors affect the clinical performance of a dressing The amount of silver content, the chemical, and physical forms of the silver, silver distribution, and even the affinity for moisture all participate in a dressing’s capability to exert a significant antimicrobial effect Marked differences exist in a variety of silver dressing products These products can be categorized as: (i) silver-delivery dressings such as Acticoatt (Smith & Nephew, Hull, UK) and Urgotul s SSD (Laboratory URGD, Chenove, France), which have silver content coated (on the surface) or impregnated into the dressing material They deliver silver to the wound site after direct contact; (ii) silver-containing dressings such as Aquacel s Ag (Cenvatec, Deeside, UK), Contreet s Foam (Coloplast, Humlebaek, Denmark), and PolyMem s Silver

A comparative study of the cytotoxicity of silver‐based dressings in monolayer cell, tissue explant, and animal models

Significance: The regeneration of healthy and functional skin remains a huge challenge due to its multilayer structure and the presence of different cell types within the extracellular matrix in an organized way. Despite recent advances in wound care products, traditional therapies based on natural origin compounds, such as plant extracts, honey, and larvae, are interesting alternatives. These therapies offer new possibilities for the treatment of skin diseases, enhancing the access to the healthcare, and allowing overcoming some limitations associated to the modern products and therapies, such as the high costs, the long manufacturing times, and the increase in the bacterial resistance. This article gives a general overview about the recent advances in traditional therapies for skin wound healing, focusing on the therapeutic activity, action mechanisms, and clinical trials of the most commonly used natural compounds. New insights in the combination of traditional products with modern treatments and future challenges in the field are also highlighted. Recent Advances: Natural compounds have been used in skin wound care for many years due to their therapeutic activities, including anti-inflammatory, antimicrobial, and cell-stimulating properties. The clinical efficacy of these compounds has been investigated through in vitro and in vivo trials using both animal models and humans. Besides the important progress regarding the development of novel extraction methods, purification procedures, quality control assessment, and treatment protocols, the exact mechanisms of action, side effects, and safety of these compounds need further research. Critical Issues: The repair of skin lesions is one of the most complex biological processes in humans, occurring throughout an orchestrated cascade of overlapping biochemical and cellular events. To stimulate the regeneration process and prevent the wound to fail the healing, traditional therapies and natural products have been used with promising results. Although these products are in general less expensive than the modern treatments, they can be sensitive to the geographic location and season, and exhibit batch-to-batch variation, which can lead to unexpected allergic reactions, side effects, and contradictory clinical results. Future Directions: The scientific evidence for the use of traditional therapies in wound healing indicates beneficial effects in the treatment of different lesions. However, specific challenges remain unsolved. To extend the efficacy and the usage of natural substances in wound care, multidisciplinary efforts are necessary to prove the safety of these products, investigate their side effects, and develop standard controlled trials. The development of good manufacturing practices and regulatory legislation also assume a pivotal role in order to improve the use of traditional therapies by the clinicians and to promote their integration into the national health system. Current trends move to the development of innovative wound care treatments, combining the use of traditional healing agents and modern products/practices, such as nanofibers containing silver nanoparticles, Aloe vera loaded into alginate hydrogels, propolis into dressing films, and hydrogel sheets containing honey.

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Traditional Therapies for Skin Wound Healing.

Clinicians now recognize that both aerobic and anaerobic microorganisms have the ability to degrade or damage host tissue at a wound site through the production of a variety of enzymes and toxins. Silver-containing dressings offer one method for controlling this polymicrobial wound bioburden, and research efforts are currently ongoing to determine their efficacy against aerobic, anaerobic, and antibiotic-resistant microorganisms. The current study aimed to determine the antimicrobial activity of a new silver-containing Hydrofiber dressing (AQUACEL Ag) on both aerobic and anaerobic microorganisms, using the zone-of-inhibition method. This method provides a measure of the ability of the dressing to make available a sufficient concentration of silver to have an antimicrobial effect. To some extent this test mimics the clinical use of the dressing and predicts its microbicidal activity at the wound-dressing interface. The results show that the silver-containing dressing makes silver available at a dressing-agar interface at a concentration that is effective against a broad range of aerobic, anaerobic, and antibiotic-resistant microorganisms. In the context of wound healing, the results showing antimicrobial activity against antibiotic-resistant microorganisms are particularly important, as the control and eradication of these organisms is a major concern within the health care profession.

Controlling wound bioburden with a novel silver-containing Hydrofiber dressing.

Partial-thickness burns are often characterized by microbial contamination and copious exudate produced during the early postburn period. Consequently, topical wound management often relies on the use of antimicrobial agents and absorbent dressings, and an AQUACEL Hydrofiber Dressing containing ionic silver has been designed to meet such needs. To assess the antimicrobial properties of the AQUACEL Hydrofiber dressing, samples were challenged with a wide variety of recognized burn wound pathogens in a simulated wound fluid model. Dressing samples were inoculated with the challenge organisms at time zero and then reinoculated on days 4 and 9 to mimic the worst-case clinical scenario. The dressing was shown to be microbicidal against aerobic and anaerobic bacteria (including antibiotic-resistant strains), yeasts, and filamentous fungi during a 14-day test period. Based on our results, the silver-containing dressing is likely to provide a barrier to infection, in addition to providing proven fluid-handling benefits of the AQUACEL Hydrofiber dressing, in the management of partial-thickness burns.

Microbicidal properties of a silver-containing hydrofiber dressing against a variety of burn wound pathogens.

Ionic silver has a long history as an antimicrobial in human health care. This article is a review of the published literature on how ionic silver may enter the body from exposure to silver-containing wound care products and its eventual metabolic fates, in an assessment of the safety during normal use of these products in wound care. Following the application to breached skin, there appears to be little evidence of localised or systemic toxicity, and this is borne out by the continuous use of silver sulfadiazine formulations for more than 50 years. Consequently, following normal use, the risk of silver ion toxicity locally and systemically is considered to be low or negligible.

The biological fate of silver ions following the use of silver-containing wound care products - a review.

An in vitro test of the efficacy of an anti-biofilm wound dressing

Objective: To assess the effectiveness of a new, next-generation antimicrobial dressing (NGAD; AQUACEL Ag+ EXTRA dressing) in managing wound exudate, infection and biofilm, and facilitating progression toward healing. Method: Clinicians from the UK and Ireland selected stalled or deteriorating wounds that were considered to be compromised by infection and/or biofilm. Only the primary dressing was replaced by the NGAD, for up to 4 weeks or as deemed clinically appropriate; otherwise, standard protocols of care were used. Evaluation forms captured the baseline and final assessment characteristics of wound status, exudate levels, skin health, wound bed appearance, signs of infection and biofilm, and wound dimensions. Results: In all, 29 wounds were suitable for inclusion in the final analysis. Following the NGAD evaluation, wound statuses were shifted from stagnant/deteriorating to mainly improved, exudate levels were shifted from moderate/high to moderate/low, and skin health was improved in 20 wounds (69%)...

A next-generation antimicrobial wound dressing: a real-life clinical evaluation in the UK and Ireland.

The objective of this work was to evaluate the safety and effectiveness of a next-generation antimicrobial wound dressing (NGAD; AQUACEL® Ag+ Extra™ dressing) designed to manage exudate, infection and biofilm. Clinicians were requested to evaluate the NGAD within their standard protocol of care for up to 4 weeks, or as long as deemed clinically appropriate, in challenging wounds that were considered to be impeded by suspected biofilm or infection. Baseline information and post-evaluation dressing safety and effectiveness data were recorded using standardised evaluation forms. This data included wound exudate levels, wound bed appearance including suspected biofilm, wound progression, skin health and dressing usage. A total of 112 wounds from 111 patients were included in the evaluations, with a median duration of 12 months, and biofilm was suspected in over half of all wounds (54%). After the introduction of the NGAD, exudate levels had shifted from predominantly high or moderate to low or moderate levels, while biofilm suspicion fell from 54% to 27% of wounds. Wound bed coverage by tissue type was generally shifted from sloughy or suspected biofilm towards predominantly granulation tissue after the inclusion of the NGAD. Stagnant (65%) and deteriorating wounds (27%) were shifted to improved (65%) or healed wounds (13%), while skin health was also reported to have improved in 63% of wounds. High levels of clinician satisfaction with the dressing effectiveness and change frequency were accompanied by a low number of dressing-related adverse events (n = 3; 2·7%) and other negative observations or comments. This clinical user evaluation supports the growing body of evidence that the anti-biofilm technology in the NGAD results in a safe and effective dressing for the management of a variety of challenging wound types.

https://www.onlinelibrary.wiley.com/doi/epdf/10.1111/iwj.12590

David Parsons

Papers

Microbicidal properties of a silver-containing hydrofiber dressing against a variety of burn wound pathogens.

The biological fate of silver ions following the use of silver-containing wound care products - a review.

An in vitro test of the efficacy of an anti-biofilm wound dressing

A next-generation antimicrobial wound dressing: a real-life clinical evaluation in the UK and Ireland.

Clinical safety and effectiveness evaluation of a new antimicrobial wound dressing designed to manage exudate, infection and biofilm