Elsevier

Burns

Volume 33, Issue 2, March 2007, Pages 139-148
Burns

Review
Effect of silver on burn wound infection control and healing: Review of the literature

https://doi.org/10.1016/j.burns.2006.06.010Get rights and content

Abstract

Silver compounds have been exploited for their medicinal properties for centuries. At present, silver is reemerging as a viable treatment option for infections encountered in burns, open wounds, and chronic ulcers. The gold standard in topical burn treatment is silver sulfadiazine (Ag-SD), a useful antibacterial agent for burn wound treatment. Recent findings, however, indicate that the compound delays the wound-healing process and that silver may have serious cytotoxic activity on various host cells. The present review aims at examining all available evidence about effects, often contradictory, of silver on wound infection control and on wound healing trying to determine the practical therapeutic balance between antimicrobial activity and cellular toxicity. The ultimate goal remains the choice of a product with a superior profile of infection control over host cell cytotoxicity.

Introduction

The final aim of burn management and therapy is wound healing and epithelization as soon as possible in order to prevent infection and to reduce functional and aesthetic after effects [1]. The use of topical chemotherapy has been fundamental in that regard and has helped to improve the survival of patients with major burns and to minimize the incidence of burn wound sepsis, a leading cause of mortality and morbidity in these patients [2]. One of the strategies that is gaining renewed attention for combating the threat of bacterial infection and preventing wound sepsis, is the use of noble metal antimicrobials the most prevalent of which is silver [3]. For centuries silver has been known to have bactericidal properties. As early as 1000 B.C., the antimicrobial properties of silver in rendering water potable were appreciated [4], [5]. Silver compounds have been exploited for their medicinal properties for centuries as well [6]. They were popular remedies for tetanus and rheumatism in the 19th century and for colds and gonorrhea before the advent of antibiotics in the early part of the 20th century [7]. A detailed historical review about the early usage of silver to treat various conditions has been recently published [8]. Interest in silver salts or silver salt solutions in the treatment of burn patients, however, completely disappeared around the Second World War [9]. It took many years for interest in silver (nitrate) to revive, under the stimulus of a publication by Moyer et al. [10]. At present, silver has reemerged as a viable treatment option for infections encountered in burns, open wounds, and chronic ulcers.

Several products have incorporated silver for use as a topical antibacterial agent, such as silver nitrate, silver sulphadiazine (SSD) (Flammazine™, Smith & Nephew Healthcare Limited, Hull, Canada) [11], silver sulphadiazine/chlorhexidine (Silverex®, Motiff Laboratories Pvt. Ltd. Kare Health specialties, Verna, Goa), SSD with cerium nitrate (Flammacerium®, Solvay, Brussels, Belgium), and silver sulphadiazine-impregnated lipidocolloid wound dressing Urgotul SSD® (Laboratories Urgo, Chenove, France) [5], [11], [12], [13]. In contrast to these silver agents, newly developed products such as Acticoat™ (Westaim Biomedical Inc., Fort Saskatchewan, Alberta, Canada) and Silverlon® (Argentum Medical, L.L.C., Lakemont, Georgia) have a more controlled and prolonged release of nanocrystalline silver to the wound area. This mode of silver delivery allows the dressings to be changed with less frequency, thereby reducing risk of nosocomial infection, cost of care, further tissue damage and patient discomfort [4], [14], [15], [16].

The gold standard in topical burn treatment is silver sulfadiazine (Ag-SD), a useful antibacterial agent for burn wound treatment. Recent findings, however, indicate that the compound delays the wound-healing process [17] and that silver may have serious cytotoxic activity on various host cells [2], [17], [18], [19], [20], [21], [22]. On the other hand, the beneficial effects of silver on wound biology due to its potent antimicrobial activity have been overlooked in general until recently. The literature is becoming replete with clinical trials purporting to show the benefits of silver therapeutics and silver-release dressings on wound repair and regeneration through its antimicrobial efficacy. Little is published, however, to show how the released silver ion influences the wound bed, or to what extent it is metabolized or deposited in the tissue. Moreover, results of the extensive literature review we conducted failed to reveal any clinical studies regarding the risks and probabilities of wounds in general to become infected, about the effect of silver dressings on already infected wounds, nor about studies comparing the effect of silver or other antiseptic dressings on prevention of wound infection.

Irrespective of the source of silver, whether released from solutions, creams and ointments or nanocrystalline silver released from commercially available new dressings, silver is highly toxic to both keratinocytes and fibroblasts [23]. Fibroblasts appear to be more sensitive to silver than keratinocytes. Consideration of the cytotoxic effects of silver and silver-based products should be taken when deciding on dressings for specific wound care strategies. This is particularly important when using keratinocyte culture, in situ, which is playing an increasing role in contemporary wound and burn care [23], [24]. Moreover, certain recent clinical studies in major burn centers have demonstrated the emergence of bacterial resistant strains mainly Escherichia coli, to silver as well as to many antibiotics following the prolonged usage of silver based dressings. The present review aims at examining all available evidence about effects, often contradictory, of silver on wound infection control and on wound healing trying to determine the practical therapeutic balance between antimicrobial activity and cellular toxicity.

Section snippets

Silver products and delivery modalities

Elemental silver requires ionization for antimicrobial efficacy [25]. Silver ion is a highly reactive species, readily binding to negatively charged proteins, RNA, DNA, chloride ions, and so on. This property lies at the heart of its antibacterial mechanism but also complicates delivery to the wound bed, because it is readily bound to proteins within the complex wound fluid [26]. Different silver delivery systems exist, including those that deliver silver from ionic compounds, such as silver

Silver products efficacy

Very few randomized prospective studies on the use of silver have been published [26] however, the role and the mechanism of action of silver ions in vivo continue to provide a steady contribution to the surgical literature [23]. For silver to be biologically active, it must be in a soluble form such as Ag+ or Ag0 clusters [34], [35] and any silver dressing efficacy is determined by total available soluble silver, not total silver in the dressing [36]. Ag0 is the metallic or uncharged form of

Silver and wound infection

The use of topical chemotherapy is fundamental to prevent infections in deep and superficial burns or extensive intermediary burns [1]. Increasingly, antibiotics, due to widespread indiscriminate prescription, are becoming less effective as pathogens are becoming more resistant to their action. Silver may be a useful prophylactic or therapeutic agent for the prevention of wound colonization by organisms that impede healing, including antibiotic-resistant bacteria [35]. It has been a choice

Silver and wound healing

Prior reported effects of silver (nitrate) on burn wounds were based primarily on clinical studies and observations. The toxicity of silver ions per se has not been an issue in burn care that has received much attention [23]. Extensive treatment of acute burn wounds with silver sulfadiazine (SSD), however, has recently raised concern about potential silver toxicity [25]. Laboratory studies confirm that both keratinocytes and fibroblasts are susceptible to lethal damage when exposed to

Conclusion

The only constant with wounds is that they are constantly changing. Practitioners should stay vigilant about the adverse effects of bacteria in wounds and keep in mind the role of infection in producing wound healing failure [27]. However, due to substantial experiences with adverse silver sulfadiazine reactions and side effects, it is appropriate to keep the possibility of a toxic silver effect in burn patients treated with slow sustained release silver-coated newly developed wound dressings

References (92)

  • P.L. Taylor et al.

    Impact of heat on nanocrystalline silver dressings. Part I. Chemical and biological properties

    Biomaterials

    (2005)
  • R.E. Hall et al.

    Inhibitory and cidal antimicrobial actions of electrically generated silver ions

    J Oral Maxillofac Surg

    (1987)
  • R. Birringer

    Nanocrystalline materials

    Mater Sci Eng

    (1989)
  • P.L. Taylor et al.

    Impact of heat on nanocrystalline silver dressings. Part II. Physical properties

    Biomaterials

    (2005)
  • S.M. Modak et al.

    Binding of silver sulfadiazine to the cellular components of pseudomonas aeruginosa

    Biochem Pharmacol

    (1973)
  • M.C. Robson

    Wound infection: a failure of wound healing caused by an imbalance of bacteria

    Surg Clin NA

    (1997)
  • M.C. Robson

    Wound infection. A failure of wound healing caused by an imbalance of bacteria

    Surg Clin North Am

    (1997)
  • K. Esuvaranathan et al.

    A study of 245 infected surgical wounds in Singapore

    J Hosp Infect

    (1992)
  • R.H. Demling et al.

    The rate of re-epithelialization across meshed skin grafts is increased with exposure to silver

    Burns

    (2002)
  • H.S. Stern

    Silver sulphadiazine and the healing of partial thickness burns: a prospective clinical trial

    Br J Plast Surg

    (1989)
  • C.P. Sawhney et al.

    Long-term experience with 1 percent topical silver sulphadiazine cream in the management of burn wounds

    Burns

    (1989)
  • G. Chaby et al.

    Topical silver sulfadiazine-induced acute renal failure

    Ann Dermatol Venereol

    (2005)
  • R.L. McCauley et al.

    In vitro toxicity of topical antimicrobial agents to human fibroblasts

    J Surg Res

    (1989)
  • V. Alt et al.

    An in vitro assessment of the antibacterial properties and cytotoxicity of nanoparticulate silver bone cement

    Biomaterials

    (2004)
  • C. Baldi et al.

    Effects of silver in isolated rat hepatocytes

    Toxico1 Lett

    (1988)
  • C.J. Coombs et al.

    Do burn patients have a silver lining?

    Burns

    (1992)
  • X.W. Wang et al.

    Tissue deposition of silver following topical use of silver sulfadiazine in extensive burns

    Burns

    (1985)
  • C.M.R. Rowland-Payne et al.

    Argyria from excessive use of topical silver sulphadiazine

    Lancet

    (1992)
  • M. Bosetti et al.

    Silver coated materials for external fixation devices: in vitro biocompatibility and genotoxicity

    Biomaterials

    (2002)
  • L. Salas Campos et al.

    Topical chemotherapy for the treatment of burns

    Rev Enferm

    (2005)
  • J.F. Fraser et al.

    Cytotoxicity of topical antimicrobial agents used in burn wounds in Australasia

    ANZ J Surg

    (2004)
  • J.B. Wright et al.

    The Comparative efficacy of two antimicrobial barrier dressings: in vitro examination of two controlled release of silver dressings

    Wounds

    (1998)
  • J.W. Richard et al.

    Acticoat™ versus Silverlon®: the truth

    J Burns Surg Wound Care

    (2002)
  • F. Fu-Ren et al.

    Bard chemical, electrochemical, gravimetric, and microscopic studies on antimicrobial silver films

    Phys Chem B

    (2002)
  • S.M. Mirsattari et al.

    Myoclonic status epilepticus following repeated oral ingestion of colloidal silver

    Neurology

    (2004)
  • H.J. Klasen

    Historical review of the use of silver in the treatment of burns. I. Early uses

    Burns

    (2001)
  • A. Gupta et al.

    Effects of halides on plasmid-mediated silver resistance in Escherichia coli

    Appl Environ Microbiol

    (1998)
  • H. Carsin et al.

    A silver sulphadiazine-impregnated lipidocolloid wound dressing to treat second-degree burns

    J Wound Care

    (2004)
  • P.M. Carneiro et al.

    A comparison of topical Phenytoin with Silverex in the treatment of superficial dermal burn wounds

    Cent Afr J Med

    (2002)
  • L.L.C. Argentum Medical

    Silverlon product information

    Accessed

    (2002)
  • R.L. Sheridan et al.

    Once-daily wound cleansing and dressing change: efficacy and cost

    J Burn Care Rehabil

    (1997)
  • L. Braydich-Stolle et al.

    In vitro cytotoxicity of nanoparticles in mammalian germline stem cells

    Toxicol Sci

    (2005)
  • P.K. Lam et al.

    In vitro cytotoxicity testing of a nanocrystalline silver dressing (Acticoat) on cultured keratinocytes

    Br J Biomed Sci

    (2004)
  • F.Q. Zhang et al.

    Comparison of the cytotoxicity in vitro among six types of nano-silver base inorganic antibacterial agents

    Zhonghua Kou Qiang Yi Xue Za Zhi

    (2005)
  • Y. Abe et al.

    Cytotoxicity of antimicrobial tissue conditioners containing silver-zeolite

    Int J Prosthodont

    (2003)
  • B. Atiyeh et al.

    State of the art in burn treatment

    World J Surg

    (2005)
  • Cited by (1057)

    View all citing articles on Scopus
    View full text