Exploring the Effects of Silver in Wound Management—What is Optimal?
- 0 Comments
- 8972 reads
In recent years, use of silver in medical healthcare devices has seen a vast increase. This increase has been largely dominated by wound dressings. Silver sulfadiazine, which has been available for approximately 40 years, provides broad-spectrum antimicrobial activity and has been widely used, particularly as a topical cream to manage burn infection. In the last 5 years, the number of available silver-containing dressings has increased. These dressings are used primarily on chronic wounds and in clinical practice are regularly applied for periods of time up to and in excess of 4 weeks. As silver dressings may be used in clinical situations other than as a temporary option, it is important that potential toxicity be considered, particularly in relation to the type and amount of silver, and as regards the risk of selecting for bacterial resistance. These factors have been recently reviewed.1
This article will consider what happens once the body absorbs silver and discuss the levels of silver required to exert a toxic effect on bacteria. In addition, it will explore the relevance of the carrier dressing to efficacy of silver and the clinical relevance of microbial kill time. It is preferable that any testimony made in respect of silver should be clinically relevant. In order to do this, data should be drawn from clinical (in-vivo) studies wherever possible. Unfortunately, few such studies exist, so much data will be drawn from available in-vitro, ex-vivo, and animal studies.
Metabolic fate of topical silver. Silver, as a component of wound dressings, antibiotic cream, and first-aid plasters, comes into contact with intact skin and breached skin on an increasingly regular basis. The penchant for silver as an antimicrobial has seen it incorporated into simple adhesive dressings for minor cuts and abrasions and is no longer reserved for “serious” wound management. Potential repercussions associated with these applications need to be acknowledged and explored. Apart from increasing the risk of contact dermatitis and selecting for resistance, there will be concerns about possible systemic and cutaneous toxicity. The interaction of metallic silver with intact skin does not cause any detectable increase in blood levels and is not of great toxicological interest. However, the recent increase in the use of silver-based wound treatments raises some concerns about the systemic effects of silver and warrants a toxicological review. Several factors influence the capacity of a metal to produce either local or systemic toxic effects. These factors include 1) the degree of absorption as influenced by solubility of the metal or its compounds, 2) the ability to bind to biological sites, and 3) the degree to which the metal complexes are sequestered, metabolized, and ultimately excreted.
1. Maillard JY, Denyer SP. Demystifying silver. EWMA Position Document: Management of Wound Infection. London, UK: Medical Education Partnership, Ltd; 2006:7–10.
2. White RJ, Cooper RA. Silver sulfadiazine: a review of the evidence. Wounds-UK. 2005;1(2);51–62.
3. Wan AT, Conyers RA, Coombs CJ, Masterton JP. Determination of silver in blood, urine, and tissues of volunteers and burn patients. Clin Chem. 1991;37(10 Pt 1):1683–1687.
4. Guy’s and St. Thomas’ NHS Foundation Trust. Silver Assay Page. Available at: http://www.medtox.org/lab/assay.asp?id=Silver. Accessed May 24, 2006.
5. Boosalis MG, McCall JT, Ahrenholz DH, Solem LD, McClain CJ. Serum and urinary silver levels in thermal injury patients. Surgery. 1992;101(1):40–43.
6. Coombs CJ, Wan AT, Masterton JP, Conyers RA, Pedersen J, Chia YT. Do burn patients have a silver lining? Burns. 1992;18(3):179–184.
7. Chaby G, Viseux V, Poulain JF, De Cagny B, Denoeux JP, Lok C. Topical silver sulfadiazine-induced acute renal failure. Ann Dermatol Venereol. 2005;132(11 Pt 1):891–893.
8. Lansdown AB, Williams A. How safe is silver in wound care? J Wound Care. 2004;13(4):131–136.
9. Harrison HN. Pharmacology of sulfadiazine silver. Its attachment to burned human and rat skin and studies of gastrointestinal absorption and extension. Arch Surg. 1979;114(3):281–285.
10. Lansdown AB, Williams A, Chandler S, Benfield S. Silver absorption and antibacterial efficacy of silver dressings. J Wound Care. 2005;14(4):155–160.
11. Chen J, Han CM, Yu CH. Change in silver metabolism after the application of nanometer silver on burn wound. Zhonghua Shao Shang Za Zhi. 2004;20(3):161–163.
12. Trop M, Novak M, Rodl S, Hellbom B, Kroell W, Goessler W. Silver-coated dressing Acticoat caused raised liver enzymes and argyria-like symptoms in burn patient. J Trauma. 2006;60(3):648–652.
13. Drake PL, Hazelwood KJ. Exposure-related health effects of silver and silver compounds: a review. Ann Occup Hyg. 2005;49(7):575–585.
14. Baldi C, Minoia C, Di Nucci A, Capodaglio E, Manzo L. Effects of silver in isolated rat hepatocytes. Toxicol Lett. 1988;41(3):261–268.
15. Fung MC, Bowen DL. Silver products for medical indications: risk-benefit assessment. J Toxicol Clin Toxicol. 1996;34(1):119–126.
16. Smoot EC 3rd, Kucan JO, Roth A, Mody N, Debs N. In vitro toxicity testing for antibacterials against human keratinocytes. Plast Reconstr Surg. 1991;87(5):917–924.
17. McCauley RL, Li YY, Poole B, et al. Differential inhibition of human basal keratinocyte growth to silver sulfadiazine and mafenide acetate. J Surg Res. 1992;52(3):276–285.
18. Hidalgo E, Dominguez C. Study of cytotoxicity mechanisms of silver nitrate in human dermal fibroblasts. Toxicol Lett. 1998;98(3):169–179.
19. Poon VK, Burd A. In vitro cytotoxicity of silver: implication for clinical wound care. Burns. 2004;30(2):140–147.
20. Schaller M, Laude J, Bodewaldt H, Hamm G, Korting HC. Toxicity and antimicrobial activity of a hydrocolloid dressing containing silver particles in an ex vivo model of cutaneous infection. Skin Pharmacol Physiol. 2004;17(1):31–36.
21. Supp AP, Neely AN, Supp DM, Warden GD, Boyce ST. Evaluation of cytotoxicity and antimicrobial activity of Acticoat Burn Dressing for management of microbial contamination in cultured skin substitutes grafted to athymic mice. J Burn Care Rehabil. 2005;26(3):238–246.
22. Cooper ML, Laxer JA, Hansbrough JF. The cytotoxic effects of commonly used topical antimicrobial agents on human fibroblasts and keratinocytes. J Trauma. 1991;31(6):755–784.
23. Serralta VW, Harrison-Belestra C, Cazzaniga AL, Davis SC, Mertz PM. Lifestyles of bacteria in wounds: presence of biofilms? WOUNDS. 2001;13(1):29–34.
24. Delissalde F, Amabile-Cuevas CF. Comparison of antibiotic susceptibility and plasmid content, between biofilm producing and non-producing clinical isolates of Pseudomonas aeruginosa. Int J Antimicrob Agents. 2004;24(4):405–408.
25. Thurman RB, Gerba CP. The molecular mechanisms of copper and silver ion disinfection of bacteria and viruses. CRC Crit Rev Environ Contr. 1989;18(4):295–315.
26. Russell AD, Hugo WB. Antimicrobial activity and action of silver. Prog Med Chem. 1994;31:351–370.
27. von Näegeli KW. Ueber oligodynamische Erscheimungen in lebenden Zellen. Neue Denschr Algemin Schweiz Gesellschaft Ges Naturweiss. 1893;XXXIII(Abt 1):174.
28. Simonetti N, Simonetti G, Bougnol F, Scalzo M. Electrochemical Ag+ for preservative use. Appl Environ Microbiol. 1992;58(12):3834–3836.
29. Bechert T, Boswald M, Lugauer S, Regenfus A, Greil J, Guggenbichler JP. The Erlanger silver catheter: in vitro results for antimicrobial activity. Infection. 1999;27(Suppl 1):S24–S29.
30. Rentz EJ. Viral pathogens and severe respiratory distress syndrome: oligodynamic Ag+ for direct immune intervention. J Nutr Environ Med. 2003;13(2):109–118.
31. Batarseh KI. Anomaly and correlation of killing in the therapeutic properties of silver (I) chelation with glutamic and tartaric acids. J Antimicrob Chemother. 2004;54(2):546–548.
32. Cliver D. Biocidal effects of silver. Final Technical Report. 1971;NAS 9-9300. University of Wisconsin, Madison USA.
33. Spacciapoli P, Buxton D, Rothstein D, Friden P. Antimicrobial activity of silver nitrate against periodontal pathogens. J Periodontal Res. 2001;36(2):108–113.
34. Garhammer P, Hiller KA, Reitinger T, Schmalz G. Metal content of saliva of patients with and without metal restorations. Clin Oral Investig. 2004;8(4):238–242.
35. Davis IJ, Richards H, Mullany P. Isolation of silver- and antibiotic-resistant Enterobacter cloacae from teeth. Oral Microbiol Immunol. 2005;20(3):191–194.
36. Bowler PG, Jones SA, Walker M, Parsons D. Microbicidal properties of a silver-containing Hydrofiber dressing against a variety of burn wound pathogens. J Burn Care Rehabil. 2004;25(2):192–196.
37. Drlica K. The mutant selection window and antimicrobial resistance. J Antimicrob Chemother. 2003;52(1):11–17.
38. Epstein BJ, Gums JG, Drlica K. The changing face of antibiotic prescribing: the mutant selection window. Ann Pharmacother. 2004;38(10):1675–1682.
39. Percival SL, Bowler PG, Russell AD. Bacterial resistance to silver in wound care. J Hosp Infect. 2005;60(1):1–7.
40. Brett DW. A discussion of silver as an antimicrobial agent: alleviating the confusion. Ostomy Wound Manage. 2006;52(1):34–41.
41. Chaw KC, Manimaran M, Tay FE. Role of silver ions in destabilization of intermolecular adhesion forces measured by atomic force microscopy in Staphylococcus epidermidis biofilms. Antimicrob Agents Chemother. 2005;49(12):4853–4859.
42. Illingworth BL, Tweden K, Schroeder RF, Cameron JD. In vivo efficacy of silver-coated (Silzone) infection-resistant polyester fabric against a biofilm-producing bacteria, Staphylococcus epidermidis. J Heart Valve Dis. 1998;7(5):524–530.
43. Sibbald RG. Introduction to bacteria and pressure ulcers: the role of silver versus traditional antimicrobials. Ostomy Wound Manage. 2003;49(Suppl 5A):3–33.
44. Parsons D, Bowler PG, Myles V, Jones S. Silver antimicrobial dressings in wound management: a comparison of antibacterial, physical and chemical characteristics. WOUNDS. 2005;17(8):222–232.
45. Snyder RJ. Managing dead space: an overview—eliminating these unwanted areas is a key to successful wound healing. Podiatry Manage. 2005;24(8):171–174.
46. Coutts P, Sibbald RG. The effect of a silver-containing Hydrofiber dressing on superficial wound bed and bacterial balance of chronic wounds. Int Wound J. 2005;2(4):348–356.
47. Richters CD, du Pont JS, Mayen I, et al. Effects of a hydrofiber dressing on inflammatory cells in rat partial-thickness wounds. WOUNDS. 2004;16(2):63–70.
48. Jones SA, Bowler PG, Walker M, Parsons D. Controlling wound bioburden with a novel silver-containing Hydrofiber dressing. Wound Repair Regen. 2004;12(3):288–294.
49. Jones S, Bowler PG, Walker M. Antimicrobial activity of silver-containing dressings is influenced by dressing conformability with a wound surface. WOUNDS. 2005;17(9):263–270.
50. White RJ, Cutting K, Kingsley A. Topical antimicrobials in the control of wound bioburden. Ostomy Wound Manage. 2006;52(8):26–58
51. Walker M, Hobot JA, Newman GR, Bowler PG. Scanning electron microscopic examination of bacterial immobilisation in a carboxymethyl cellulose (AQUACEL) and alginate dressings. Biomaterials. 2003;24(5):883–890.
52. Thomas S. MRSA and the use of silver dressings: overcoming bacterial resistance. Available at: http://www.worldwidewounds.com/2004/november/Thomas/Introducing-Silver-D.... Accessed June 2, 2006.
53. Silver S, Phung LT, Silver G. Silver as biocides in burn and wound dressings and bacterial resistance to silver compounds. J Ind Microbiol Biotechnol. 2006;33(7):627–634.