Silver-Releasing Dressings in Treating Chronic Wounds

Summary and Conclusions

SBU’s appraisal of the evidence

Silver-releasing dressings are used to treat chronic (hard-to-heal) wounds, ie, wounds that do not heal within the time expected. Common causes of chronic wounds include poor blood circulation or infection in the wound. Silver-containing dressings release silver ions intended to reduce the amount of bacteria in the wound and thereby promote healing.

• The scientific evidence is insufficient to determine whether silver dressings differ from dressings without silver in terms of effects on the percentage of healed wounds, wound size, pain, quality of life, percentage of infections, and use of antibiotics in treating chronic wounds. The reason is that too few studies of sufficient quality are available. The studies reviewed have not identified serious side effects or complications related to silver dressings, but they were not designed to study this specifically.
• The scientific evidence is insufficient to draw conclusions on the cost-effectiveness of silver dressings since too few studies are available.
• No controlled studies have investigated the effects of silver dressings on bacteria in chronic wounds.
• Well-designed studies are required to determine the effects of silver dressings and the appropriate indications for treating chronic wounds. It is important to consider the risk for development of bacteria that are resistant against antibiotics and the risks for negative environmental effects from using silver dressings. Hence, until further notice, silver dressings should be used only within the framework of controlled trials, or in other systematic follow-ups and compilations of their effects.

Technology and target group

Silver has been used in health care for many years to treat various infections. Dressings and creams containing silver are used primarily in treating chronic wounds and burns. Silver-releasing dressings contain silver (usually in the form of silver salt or nanoparticles) that is released as positively charged ions when in contact with liquid. The silver is targeted at reducing the bacteria concentration in the wound, thereby promoting the healing process. The use of silver dressings has been questioned since silver is a heavy metal with toxic properties that can present risks for human health, animals, and the environment. Another risk that has been discussed is that bacteria can develop resistance against silver, and this resistance could be linked to resistance towards antibiotics.

In this assessment, patients with chronic wounds comprise the target group for treatment with silver dressings.

Primary questions

• What are the effects of silver dressings in treating chronic wounds as measured by the percentage of wounds healed, wound size, pain, quality of life, percentage of infections, and use of antibiotics?
• What is the cost of treating wounds with silver dressings? Is treatment cost-effective?
• Does the silver in silver-containing dressings have an antibacterial effect in the wound?
• Is there a risk for bacteria to develop resistance against silver and antibiotics?

Patient benefit

The scientific evidence is insufficient* to draw conclusions on the effects that silver dressings might have on the percentage of healed wounds, wound size, pain, quality of life, percentage of infections, and use of antibiotics in treating chronic wounds.

This assessment included 6 randomized controlled trials. Two of those studies were judged to be of medium quality, and they provide the basis for the conclusions. The remaining 4 studies were judged to be of low quality. One of the medium-quality studies shows greater improvement in terms of wound size in the group treated with silver dressings. The second study shows no difference between silver dressings and dressings without silver in terms of the percentage of wounds healed and in quality of life. No serious side effects or complications related to silver dressings were identified in the studies reviewed.

No controlled studies have investigated the effects of silver dressings on bacteria in chronic wounds.

Silver resistance and its underlying mechanisms have been documented in experimental and clinical studies, but the clinical importance of these findings is unclear. Likewise, experiments have shown that bacteria exposed to silver can develop antibiotic resistance since the mechanisms that bacteria use to develop and spread silver resistance are, to some extent, the same mechanisms that bacteria use to develop antibiotic resistance.

Economic aspects

The scientific evidence is insufficient* to draw conclusions on the cost-effectiveness of silver dressings.

* Criteria for Evidence Grading SBU’s Conclusions
Evidence Grade 1 – Strong Scientific Evidence. The conclusion is corroborated by at least two independent studies with high quality, or a good systematic overview.
Evidence Grade 2 – Moderately Strong Scientific Evidence. The conclusion is corroborated by one study with high quality, and at least two studies with medium quality.
Evidence Grade 3 – Limited Scientific Evidence. The conclusion is corroborated by at least two studies with medium quality.
Insufficient Scientific Evidence – No conclusions can be drawn when there are not any studies that meet the criteria for quality.
Contradictory Scientific Evidence – No conclusions can be drawn when there are studies with the same quality whose findings contradict each other.

This summary is based on a report prepared by SBU in collaboration with Anna-Christina Ek, Professor Emeritus, Faculty of Health Sciences, Linköping University; Margareta Lindgren, Senior Lecturer, Faculty of Health Sciences, Linköping University; Åsa Melhus, Associate Professor, Uppsala University. It has been reviewed by Christina Lindholm, Professor, Högskolan Dalarna, and Folke Sjöberg, Professor, Faculty of Health Sciences, Linköping University. Project manager: Karin Rydin, SBU.

The complete report is available in Swedish.

SBU Alert is a service provided by SBU in collaboration with the Medical Products Agency, the National Board of Health and Welfare, and the Swedish Association of Local Authorities and Regions.

References

1. Harding KG, Morris HL, Patel GK. Science, medicine and the future: healing chronic wounds. BMJ 2002;324:160-3.
2. Lo SF, Chang CJ, Hu WY, Hayter M, Chang YT. The effectiveness of silver-releasing dressings in the management of non-healing chronic wounds: a meta-analysis. J Clin Nurs 2009;18:716-28.
3. Gorecki C, Brown JM, Nelson EA, Briggs M, Schoonhoven L, Dealey C, et al. Impact of pressure ulcers on quality of life in older patients: a systematic review. J Am Geriatr Soc 2009;57:1175-83.
4. Spilsbury K, Nelson A, Cullum N, Iglesias C, Nixon J, Mason S. Pressure ulcers and their treatment and effects on quality of life: hospital inpatient perspectives. J Adv Nurs 2007;57:494-504.
5. Bowler PG, Duerden BI, Armstrong DG. Wound microbiology and associated approaches to wound management. Clin Microbiol Rev 2001;14:244-69.
6. Sussman C, Bates-Jensen B. Wound care: A collaborative practice manual for health professionals. 3rd ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2007. p 21-51.
7. Bryant RA, Nix DP. Acute & chronic wounds: Current management concepts. 3rd ed. St Louis: Mosby Elsevier; 2007.
8. Edwards R, Harding KG. Bacteria and wound healing. Curr Opin Infect Dis 2004;17:91-6.
9. White RJ, Cutting KF. Critical colonization – the concept under scrutiny. Ostomy Wound Manage 2006;52:50-6.
10. Svårläkta sår – Vårdprogram för Sydöstra sjukvårdsregionen. Landstinget i Jönköping, Kalmar och Östergötland; 2009.
11. Lansdown AB. Silver in health care: antimicrobial effects and safety in use. Curr Probl Dermatol 2006;33:17-34.
12. Yang W, Shen C, Ji Q, An H, Wang J, Liu Q, et al. Food storage material silver nanoparticles interfere with DNA replication fidelity and bind with DNA. Nanotechnology 2009;20:85102.
13. Lansdown AB. Silver. I: Its antibacterial properties and mechanism of action. J Wound Care 2002;11:125-30.
14. Dibrov P, Dzioba J, Gosink KK, Hase CC. Chemiosmotic mechanism of antimicrobial activity of Ag(+) in Vibrio cholerae. Antimicrob Agents Chemother 2002;46:2668-70.
15. Choi O, Deng KK, Kim NJ, Ross L Jr, Surampalli RY, Hu Z. The inhibitory effects of silver nanoparticles, silver ions, and silver chloride colloids on microbial growth. Water Res 2008;42:3066-74.
16. Sharma VK, Yngard RA, Lin Y. Silver nanoparticles: green synthesis and their antimicrobial activities. Adv Colloid Interface Sci 2009;145:83-96.
17. Schierholz JM, Wachol-Drewek Z, Lucas LJ, Pulverer G. Activity of silver ions in different media. Zentralbl Bakteriol 1998;287:411-20.
18. Gupta A, Maynes M, Silver S. Effects of halides on plasmid-mediated silver resistance in Escherichia coli. Appl Environ Microbiol 1998;64:5042-5.
19. Silver S, Phung le T, Silver G. Silver as biocides in burn and wound dressings and bacterial resistance to silver compounds. J Ind Microbiol Biotechnol 2006;33:627-34.
20. Brett DW. A discussion of silver as an antimicrobial agent: alleviating the confusion. Ostomy Wound Manage 2006;52:34-41.
21. Lok CN, Ho CM, Chen R, He QY, Yu WY, Sun H, et al. Silver nanoparticles: partial oxidation and antibacterial activities. J Biol Inorg Chem 2007;12:527-34.
22. Matsumura Y, Yoshikata K, Kunisaki S, Tsuchido T. Mode of bactericidal action of silver zeolite and its comparison with that of silver nitrate. Appl Environ Microbiol 2003;69:4278-81.
23. Kim JS, Kuk E, Yu KN, Kim JH, Park SJ, Lee HJ, et al. Antimicrobial effects of silver nanoparticles. Nanomedicine 2007;3:95-101.
24. Tammelin A, Lindholm C, Hambraeus A. Chronic ulcers and antibiotic treatment. J Wound Care 1998;7:435-7.
25. Karlsson L, Lindroth K, Elowson S, Persson A, Eriksson M, Midtvedt A-C, et al. Punktprevalensstudie vid särskilda boenden i Västra Götalands län. Läkartidningen 2006;103:3080-3.
26. Michaels JA, Campbell B, King B, Palfreyman SJ, Shackley P, Stevenson M. Randomized controlled trial and cost-effectiveness analysis of silver-donating antimicrobial dressings for venous leg ulcers (VULCAN trial). Br J Surg 2009;96:1147-56.
27. Lazareth I, Meaume S, Sigal-Grinberg ML, Combemale P, Le Guyadec T, Zagnoli A, et al. The role of a silver releasing lipido-colloid contact layer in venous leg ulcers presenting inflammatory signs suggesting heavy bacterial colonization: results of a randomized controlled study. Wounds: A Compendium of Clinical Research & Practice 2008;20:158-66.
28. Jørgensen B, Price P, Andersen KE, Gottrup F, Bech-Thomsen N, Scanlon E, et al. The silver-releasing foam dressing, Contreet Foam, promotes faster healing of critically colonised venous leg ulcers: a randomised, controlled trial. Int Wound J 2005;2:64-73.
29. Dimakakos E, Katsenis K, Kalemikerakis J, Arkadopoulos N, Mylonas S, Arapoglou V, et al. Infected venous leg ulcers: management with silver-releasing foam dressing. Wounds: A Compendium of Clinical Research & Practice 2009;21:4-8.
30. Meaume S, Vallet D, Morere MN, Teot L. Evaluation of a silver-releasing hydroalginate dressing in chronic wounds with signs of local infection. J Wound Care 2005;14:411-9.
31. Jude EB, Apelqvist J, Spraul M, Martini J. Prospective randomized controlled study of Hydrofiber dressing containing ionic silver or calcium alginate dressings in non-ischaemic diabetic foot ulcers. Diabet Med 2007;24:280-8.
32. Chambers H, Dumville JC, Cullum N. Silver treatments for leg ulcers: a systematic review. Wound Repair Regen 2007;15:165-73.
33. Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT. Topical silver for treating infected wounds. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD005486. DOI: 10.1002/14651858.CD005486.pub2.
34. Bergin S, Wraight P. Silver based wound dressings and topical agents for treating diabetic foot ulcers. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD005082. DOI: 10.1002/14651858.CD005082.pub2.
35. Sibbald RG, Contreras-Ruiz J, Coutts P, Fierheller M, Rothman A, Woo K. Bacteriology, inflammation, and healing: a study of nanocrystalline silver dressings in chronic venous leg ulcers. Adv Skin Wound Care 2007;20:549-58.
36. Verdu Soriano J, Rueda Lopez J, Martinez Cuervo F, Soldevilla Agreda J. Effects of an activated charcoal silver dressing on chronic wounds with no clinical signs of infection. J Wound Care 2004;13:419,421-3.
37. Jelenko C 3rd. Silver nitrate resistant E. coli: report of case. Ann Surg 1969;170:296-9.
38. Hendry AT, Stewart IO. Silver-resistant Enterobacteriaceae from hospital patients. Can J Microbiol 1979;25:915-21.
39. Haefeli C, Franklin C, Hardy K. Plasmid-determined silver resistance in Pseudomonas stutzeri isolated from a silver mine. J Bacteriol 1984;158:389-92.
40. Grewal JS, Tiwari RP. Resistance to metal ions and antibiotics in Escherichia coli isolated from foodstuffs. J Med Microbiol 1990;32:223-6.
41. Gupta A, Matsui K, Lo JF, Silver S. Molecular basis for resistance to silver cations in Salmonella. Nat Med 1999;5:183-8.
42. Klaus T, Joerger R, Olsson E, Granqvist CG. Silver-based crystalline nanoparticles, microbially fabricated. Proc Natl Acad Sci U S A 1999;96:13611-4.
43. Grewal JS, Tiwari RP. Resistance to antibiotics, metals, hydrophobicity and klebocinogeny of Klebsiella pneumoniae isolated from foods. Cytobios 1999;98:113-23.
44. Davis IJ, Richards H, Mullany P. Isolation of silver- and antibiotic-resistant Enterobacter cloacae from teeth. Oral Microbiol Immunol 2005;20:191-4.
45. Johnson TJ, Siek KE, Johnson SJ, Nolan LK. DNA sequence and comparative genomics of pAPEC-O2-R, an avian pathogenic Escherichia coli transmissible R plasmid. Antimicrob Agents Chemother 2005;49:4681-8.
46. Parikh RY, Singh S, Prasad BL, Patole MS, Sastry M, Shouche YS. Extracellular synthesis of crystalline silver nanoparticles and molecular evidence of silver resistance from Morganella sp.: towards understanding biochemical synthesis mechanism. Chembiochem 2008;9:1415-22.
47. Shakibaie MR, Kapadnis BP, Dhakephalker P, Chopade BA. Removal of silver from photographic wastewater effluent using Acinetobacter baumannii BL54. Can J Microbiol 1999;45:995-1000.
48. Li XZ, Nikaido H, Williams KE. Silver-resistant mutants of Escherichia coli display active efflux of Ag+ and are deficient in porins. J Bacteriol 1997;179:6127-32.
49. Silver S. Bacterial silver resistance: molecular biology and uses and misuses of silver compounds. FEMS Microbiol Rev 2003;27:341-53.
50. Percival SL, Woods E, Nutekpor M, Bowler P, Radford A, Cochrane C. Prevalence of silver resistance in bacteria isolated from diabetic foot ulcers and efficacy of silver-containing wound dressings. Ostomy Wound Manage 2008;54:30-40.
51. Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR). Assessment of the antibiotic resistance effects of biocides. European Commission, Directorate-General for Health & Consumers. 2009.
52. Kaur P, Vadehra DV. Mechanism of resistance to silver ions in Klebsiella pneumoniae. Antimicrob Agents Chemother 1986;29:165-7.
53. Nies DH. Efflux-mediated heavy metal resistance in prokaryotes. FEMS Microbiol Rev 2003;27:313-39.
54. Gupta A, Phung LT, Taylor DE, Silver S. Diversity of silver resistance genes in IncH incompatibility group plasmids. Microbiology 2001;147:3393-402.
55. Deshpande LM, Chopade BA. Plasmid mediated silver resistance in Acinetobacter baumannii. Biometals 1994;7:49-56.
56. McHugh GL, Moellering RC, Hopkins CC, Swartz MN. Salmonella typhimurium resistant to silver nitrate, chloramphenicol, and ampicillin. Lancet 1975;1:235-40.
57. Bridges K, Kidson A, Lowbury EJ, Wilkins MD. Gentamicin- and silver-resistant pseudomonas in a burns unit. Br Med J 1979;1:446-9.
58. Markowitz SM, Smith SM, Williams DS. Retrospective analysis of plasmid patterns in a study of burn unit outbreaks of infection due to Enterobacter cloacae. J Infect Dis 1983;148:18-23.
59. Mayer KH, Hopkins JD, Gilleece ES, Chao L, O’Brien TF. Molecular evolution, species distribution, and clinical consequences of an endemic aminoglycoside resistance plasmid. Antimicrob Agents Chemother 1986;29:628-33.
60. Pirnay JP, De Vos D, Cochez C, Bilocq F, Pirson J, Struelens M, et al. Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone. J Clin Microbiol 2003;41:1192-202.
61. Grosell M, Högstrand C, Wood CM, Hansen HJ. A nose-to-nose comparison of the physiological effects of exposure to ionic silver versus silver chloride in the European eel (Anguilla anguilla) and the rainbow trout (Oncorhynchus mykiss). Aquat Toxicol 2000;48:327-42.
62. Griffitt RJ, Hyndman K, Denslow ND, Barber DS. Comparison of molecular and histological changes in zebrafish gills exposed to metallic nanoparticles. Toxicol Sci 2009;107:404-15.
63. Stockholms stad 2009. Miljöbarometern, avloppsrening. http://miljobarometern.stockholm.se.
64. Miljöstyrningsrådet 2007. Bakgrundsdokument till miljöstyrningsrådets upphandlingskriterier för förbandsartiklar.
65. Avfall Sverige. Deponering. http://www.avfallsverige.se.
66. Produkter för sårbehandling upphandlade i Region Skåne 2007–2009, version oktober 2007, artikelnummer 16362.
67. Ragnarson Tennvall G, Hjelmgren J. Behandling av venösa bensår kostsamt för sjukvård och samhälle. Värdet av förebyggande insatser måste utredas mer, visar studie. Läkartidningen 2005;102:3027-9.
68. Leaper DJ. Silver dressings: their role in wound management. Int Wound J 2006;3:282-94.
69. Biatain Ag vs Biatain in the treatment of leg ulcers. ClinicalTrials.gov identifier: NCT00807664.
70. An Investigation Evaluating the Efficacy of an Absorbent Foam Dressing Containing Silver (Mepilex Ag) Versus the Same Dressing Without Silver Used on Subjects With Venous Leg Ulcers or Mixed Ulcers. ClinicalTrials.gov identifier: NCT01036438.
71. Bishop JB, Phillips LG, Mustoe TA, VanderZee AJ, Wiersema L, Roach DE, et al. A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers. J Vasc Surg 1992;16:251-7.
72. Huang Y, Li X, Liao Z, Zhang G, Liu Q, Tang J, et al. A randomized comparative trial between Acticoat and SD-Ag in the treatment of residual burn wounds, including safety analysis. Burns 2007;33:161-6.
73. Munter KC, Beele H, Russell L, Crespi A, Grochenig E, Basse P, et al. Effect of a sustained silver-releasing dressing on ulcers with delayed healing: the CONTOP study. J Wound Care 2006;15:199-206.