Robert E. Burrell

EFFICACY OF TOPICAL SILVER AGAINST FUNGAL BURN WOUND PATHOGENS

BACKGROUND Fungal infections of burn wounds have become an important cause of burn-associated morbidity and mortality. The nature of fungal infections dictates aggressive treatment to minimize the morbidity associated with these infections. Persons with large total body surface area burns are particularly susceptible to fungal infections and are treated in such a manner as to minimize their risk of infection. METHODS This study examined the in vitro fungicidal efficacy of a variety of different topical agents. By placing fungal inocula in contact with mafenide acetate, silver nitrate, silver sulfadiazine, and a nanocrystalline silver-coated dressing, we determined the kill kinetics of these topical agents against a spectrum of common burn wound fungal pathogens. RESULTS The topical antimicrobials that were tested demonstrated varying degrees of efficacy against these pathogens. CONCLUSION The nanocrystalline silver-based dressing provided the fastest and broadest-spectrum fungicidal activity and may make it a good candidate for use to minimize the potential of fungal infection, thereby reducing complications that delay wound healing.

Anti-inflammatory activity of nanocrystalline silver in a porcine contact dermatitis model

The anti-inflammatory activity of nanocrystalline silver was examined using a porcine model of contact dermatitis. Inflammation was induced with dinitrochlorobenzene and then treated daily with nanocrystalline silver dressings, 0.5% silver nitrate, or saline. Erythema, edema, and histological data showed that nanocrystalline silver-treated pigs had near-normal skin after 72 hours, while other treatment groups remained inflamed. The decreased inflammation in the nanocrystalline silver-treated group was associated with increased inflammatory cell apoptosis, a decreased expression of proinflammatory cytokines, and decreased gelatinase activity. Silver nitrate treatments induced apoptosis in all cell types, including keratinocytes, resulting in delayed wound healing. These results demonstrate that nanocrystalline silver had a direct anti-inflammatory effect in the porcine contact dermatitis model that improved the overall outcome of the healing process. These data offer support that a species of silver (e.g., Ag(0)) that is uniquely associated with nanocrystalline silver may be responsible for the anti-inflammatory activity and improvement in healing.

Comparison of in vitro disc diffusion and time kill‐kinetic assays for the evaluation of antimicrobial wound dressing efficacy

There is a plethora of new silver‐containing dressings on the market today. Various manufacturers attempt to show that their dressings are the most efficacious and therefore should be preferentially employed by health care workers based on the results of their in vitro tests. However, there have been no studies that clearly identify which tests are appropriate for comparison purposes. The purpose of this study was to determine which in vitro test is most appropriate for evaluating the antimicrobial efficacy of silver‐containing dressings. This was done by testing seven silver‐containing dressings and two non‐silver‐containing topical agents against 17 clinically relevant microorganisms using zone of inhibition assays and time‐kill kinetic assays in complex media. The results for the two assays were then correlated to determine whether the methods generated similar results. It was determined that the two methods do not correlate at all. This is most likely a result of the silver interacting with the media in the zone of inhibition test, thus invalidating the results of this test. We therefore conclude that zone of inhibition data generated for silver‐containing dressings is of little value when assessing antimicrobial efficacy and that time‐kill assays are of greater use.

Healing of porcine donor sites covered with silver‐coated dressings

OBJECTIVE To compare rates of healing of donor sites in pigs between those dressed with silver-coated dressings and those dressed with petrolatum-impregnated absorbent gauze. DESIGN Open study with each animal acting as its own control. SETTING University research facility, Canada. ANIMALS 6 young specific-pathogen-free domestic pigs. INTERVENTIONS A total of 72 wounds about 1 cm x 2 cm x 0.4 mm were made in rows of eight on each pig with a dermatome. They were divided into three groups of 24, and dressed with petrolatum gauze, or silver-coated dressings moistened with sterile water either once only or daily for 10 days. All dressings were secured in place with an elastic bandage. MAIN OUTCOME MEASURES Erythema, infection, epidermal migration, and healing. RESULTS Wounds dressed with moistened silver-coated dressings re-epithelialised significantly more quickly. This resulted in complete re-epithelialisation within 70% of the time taken by those wounds dressed with petrolatum gauze. CONCLUSION Silver-coated dressings provide a moist environment for the healing wound combined with an effective antimicrobial agent, and this significantly accelerates healing compared with wounds dressed with traditional petrolatum gauze dressings.

A consensus approach to wound care in epidermolysis bullosa

BACKGROUND Wound care is the cornerstone of treatment for patients with epidermolysis bullosa (EB); however, there are currently no guidelines to help practitioners care for these patients. OBJECTIVES The objective of this study was to generate a list of recommendations that will enable practitioners to better care for patients with EB. METHODS An expert panel generated a list of recommendations based on the best evidence available. The recommendations were translated into a survey, and sent to other EB experts to generate consensus using an online-based modified Delphi method. The list was refined and grouped into themes and specific recommendations. RESULTS There were 15 respondents (45% response rate), with significant experience in the EB field (>10 years [67%]). Respondents included physicians (67%), nurses (17%), and allied health professionals (7%). There was more than 85% agreement for all the proposed items. These were further refined and grouped into 5 main themes (assessment and management of factors that impair healing, patient-centered concerns, local wound care, development of an individualized care plan, and organizational support) and 17 specific recommendations. LIMITATIONS There is a paucity of scientific evidence with most recommendations based on expert opinion. CONCLUSIONS These recommendations will provide practitioners with a framework for caring for these patients. Additional scientific research including effectiveness studies for everyday practice and expert consensus, may further refine these recommendations.

Evaluating antimicrobial efficacy of new commercially available silver dressings

Prevention and treatment of bacterial colonised/infected wounds are critical. Many commercially available silver dressings claim broad‐spectrum bactericidal activity over days and are indicated for serious conditions including burns and ulcers. However, there is no peer‐reviewed literature available for many newer dressings. This study compared the activity of some of these dressings. Six silver‐containing dressings were compared using log reduction, silver release and corrected zone of inhibition assays. Only the nanocrystalline silver dressing was bactericidal against Staphylococcus aureus, and the only other dressing that produced any log reduction was a silver collagen matrix dressing. These two dressings and a silver alginate dressing produced zones of inhibition, although the collagen matrix and alginate dressings had decreasing zone sizes over time, and the latter liquefied after five transfers. The remaining dressings (two ionic silver foam dressings and a silver sulphate dressing) did not produce zones of inhibition. For the foam, alginate and collagen matrix dressings, antimicrobial activity was related to silver release. The silver sulphate dressing released large quantities of silver, but only through the dressing edges, as the wound‐contacting surface appeared to be hydrophobic. The results of this study emphasise the importance of confirming product claims regarding silver dressing efficacy.

Anti-inflammatory activity of nanocrystalline silver-derived solutions in porcine contact dermatitis

BackgroundNanocrystalline silver dressings have anti-inflammatory activity, unlike solutions containing Ag+ only, which may be due to dissolution of multiple silver species. These dressings can only be used to treat surfaces. Thus, silver-containing solutions with nanocrystalline silver properties could be valuable for treating hard-to-dress surfaces and inflammatory conditions of the lungs and bowels. This study tested nanocrystalline silver-derived solutions for anti-inflammatory activity.MethodsInflammation was induced on porcine backs using dinitrochlorobenzene. Negative and positive controls were treated with distilled water. Experimental groups were treated with solutions generated by dissolving nanocrystalline silver in distilled water adjusted to starting pHs of 4 (using CO2), 5.6 (as is), 7, and 9 (using Ca(OH)2). Solution samples were analyzed for total silver. Daily imaging, biopsying, erythema and oedema scoring, and treatments were performed for three days. Biopsies were processed for histology, immunohistochemistry (for IL-4, IL-8, IL-10, TNF-α, EGF, KGF, KGF-2, and apoptotic cells), and zymography (MMP-2 and -9). One-way ANOVAs with Tukey-Kramer post tests were used for statistical analyses.ResultsAnimals treated with pH 7 and 9 solutions showed clear visual improvements. pH 9 solutions resulted in the most significant reductions in erythema and oedema scores. pH 4 and 7 solutions also reduced oedema scores. Histologically, all treatment groups demonstrated enhanced re-epithelialisation, with decreased inflammation. At 24 h, pMMP-2 expression was significantly lowered with pH 5.6 and 9 treatments, as was aMMP-2 expression with pH 9 treatments. In general, treatment with silver-containing solutions resulted in decreased TNF-α and IL-8 expression, with increased IL-4, EGF, KGF, and KGF-2 expression. At 24 h, apoptotic cells were detected mostly in the dermis with pH 4 and 9 treatments, nowhere with pH 5.6, and in both the epidermis and dermis with pH 7. Solution anti-inflammatory activity did not correlate with total silver content, as pH 4 solutions contained significantly more silver than all others.ConclusionsNanocrystalline silver-derived solutions appear to have anti-inflammatory/pro-healing activity, particularly with a starting pH of 9. Solutions generated differently may have varying concentrations of different silver species, only some of which are anti-inflammatory. Nanocrystalline silver-derived solutions show promise for a variety of anti-inflammatory treatment applications.

Atomic force microscopy: A nanoscopic view of microbial cell surfaces

The atomic force microscope (AFM) is a powerful instrument for microbiological investigation. It has evolved from an imaging tool used to investigate microbial surfaces at high resolution in their physiological environment into a lab-on-a-tip device, which allows more quantitative analysis of biological samples (from molecules to cells) in aqueous liquids. Atomic force microscopy provides information about the nanoscale architecture of microbes and about the localization and interactions of their individual constituents. Microbial interactions play essential roles in biology, medicine, ecology, biotechnology, food science and contribute to phenomena as varied as bacterial infections, biofilm formation, and bacterial adhesion to surfaces. In this review, we focus on recent developments offered by the rapid advances in AFM imaging and force spectroscopy with emphasizes on microbial research.

Does nanocrystalline silver have a transferable effect

This study examined the mechanism of nanocrystalline silver antiinflammatory activity, and tested nanocrystalline silver for systemic antiinflammatory effects. Secondary ion mass spectroscopy of skin treated directly with nanocrystalline silver for 24 hours showed that at skin surfaces there were significant deposits at weights corresponding to Ag, AgO, AgCl, AgNO3, Ag2O, and silver clusters Ag2‐6, but silver penetration was minimal. To test for translocation of the effect, a porcine contact dermatitis model in which wounds were induced on one side of the back and then treated with nanocrystalline silver on the opposite side of the back was used. Visual and histological data showed improvement relative to animals treated with saline only. Significantly increased induction of apoptosis in the inflammatory cells present in the dermis was observed with remote nanocrystalline silver treatments. In addition, immunohistochemical analysis showed decreased levels of proinflammatory cytokines tumor necrosis factor‐α and interleukin‐8, and increased levels of antiinflammatory cytokine interleukin‐4, epidermal growth factor, keratinocyte growth factor, and keratinocyte growth factor‐2. Thus, the antiinflammatory effects of nanocrystalline silver appear to be induced by interactions with cells in the top layers of the skin, which then release biological signals resulting in widespread antiinflammatory activity.

Microbial Biofilms and Chronic Wounds

Background is provided on biofilms, including their formation, tolerance mechanisms, structure, and morphology within the context of chronic wounds. The features of biofilms in chronic wounds are discussed in detail, as is the impact of biofilm on wound chronicity. Difficulties associated with the use of standard susceptibility tests (minimum inhibitory concentrations or MICs) to determine appropriate treatment regimens for, or develop new treatments for use in, chronic wounds are discussed, with alternate test methods specific to biofilms being recommended. Animal models appropriate for evaluating biofilm treatments are also described. Current and potential future therapies for treatment of biofilm-containing chronic wounds, including probiotic therapy, virulence attenuation, biofilm phenotype expression attenuation, immune response suppression, and aggressive debridement combined with antimicrobial dressings, are described.