The Use and Efficacy of Silver Dressings Introduction Historical Use of Silver The use of silver as a prophylactic treatment dates back to about 1000 BC, when the ancient Greeks and Romans used it as a disinfectant, placing silver coins in jars of water and other liquids to sterilize the liquids.1,2 Early in the 19th Century the antimicrobial activity of the silver ion was identified,2 and in 1920’s the US Food and Drug Administration accepted colloidal silver as being effective for wound management.2,3 Over the past 25 years, the medical and scientific communities have developed a body of research which demonstrates the safety and efficacy of silver as a therapeutic tool.3,4,5 Some basic mechanisms of action which have been identified through scientific research are: •Degrade bacterial enzymes by stimulating K+ ion release. •Cell wall degradation. •Inhibit cell mitotic activity. •Increase stimulation of bacterial cytoplasmic abnormalities. •Interact with DNA bases.6,7 Measurement of Antibacterial Activity Silver is currently one of the more popular topical antiseptic agents that has been incorporated into dressings. There is little doubt as to the antibacterial properties of silver, but clinical trials have utilized varying organisms and methodologies which has led to difficulty in interpreting comparisons between dressings. The levels of silver ions released by dressings in vitro have been measured and presented in several ways, including: •Parts per million: Expression of silver concentration as parts per million (ppm) has been used and 5-50 parts of silver per million is toxic to most bacteria.8 For example, TRIACT with Silver releases 50 - 120ppm. •Log reduction: Many studies have used a log10 reduction in bacteria to assess microbicidal activity. A 103 reduction is considered microbicidal.9,10 Silver dressings are bactericidal and fungicidal, and can be effective against resistant organisms or known pathogens such as MRSA and Pseudomonas.8,11,12,13 Conclusion Thus far, research on the antimicrobial efficacy of silver has been limited to in vitro studies, and despite the data on the microbicidal properties of silver, some debate exists as to the effectiveness of silver dressings in wound healing. Ultimately, the use of silver dressings in affecting positive outcomes in wound healing is best evaluated through clinical use of the dressings. Although there are very few controlled randomized clinical trials in vivo, a recent study compared the efficacy of a silver contact layer with the same dressing in a non-silver formulation. After 8 weeks, the wounds covered with the silver dressing exhibited better wound closure (P = 0.002) than the wounds covered with the control (non-silver) dressing.14 Advantages of Silver Dressings Silver dressings from Hollister Wound Care offer many advantages, including: •Effective: In vitro studies show sustained silver release that is effective against bacteria most frequently associated with wound infections, including MRSA, Streptoccus pyogenes and Pseudomonas aeruginosa. This antimicrobial activity is sustained for the full duration of the dressings’ wear-time (see Instructions for Use). •Versatile: Available in a variety of dressings for managing a wide array of wounds •Simple: The dressings do not need to be activated with saline or H20. The silver in Restore dressings is released from contact with wound exudate. Contents n Triact Technology with Silver: Description and general characteristics . ....................... 2-3 n The silver ion: Antibacterial mechanism of action . ............................................................. 4-5 n Products featuring TRIACT Technology with Silver ............................................................... 6-7 n In vitro studies on the antibacterial efficacy of the TRIACT with Silver interface .................. 8-9 n RESTORE Calcium Alginate dressing with Silver ............................................................ 10 n In Vitro studies on the antibacterial efficacy of Restore Calcium Alginate Silver dressing ...... 11 n Frequently Asked Questions .............................................................................................. 12 n References ......................................................................................................................... IBC 1 Triact Technology Description and general characteristics Composition and properties Restore Contact Layer, Silver is a sterile non-adhesive, non-occlusive, antimicrobial wound contact dressing, composed of a polyester mesh with a matrix comprised of hydrocolloid particles (carboxymethylcellulose), cohesion polymers, petrolatum and silver (2.25mg/sq.inch). Structure of the dressing mesh The TRIACT mesh is a 100% polyester textile, non-deformable, continuous yarn, coated with the TRIACT with Silver matrix. The non-deformable nature of the mesh and its constantly open pores help avoid maceration and allows exudate to pass through into the outer absorbent layers without sticking. The locked net structure of the mesh provides a continuous multifilament, reducing potential for microfiber shed in the wound. Flexible filaments allow the dressing to conform to a variety of wound types and body contours. 2 with Silver: Mechanism of action When in contact with exudate, a gel is formed, providing a moist environment that promotes healing. In addition, the silver ion is released from the silver sulfate molecule. This is ionic (Ag+) silver. The dressing sustains antibacterial activity for up to 7 days in in vitro studies. The dressing is non-adhesive, so removal is virtually pain-free and helps minimize damage to newly formed surrounding skin. It is ideal for use on wounds with fragile periwound skin. Dressing changes are recommended every 1 to 3 days, depending on the wound and the healing progression. Shown to be effective (at least 4 log reduction) against bacteria associated with wound infections including: • Streptococcus pyogenes • Pseudomonas aeruginosa • MRSA Microscopic view of the CMC material surrounding the TRIACT matrix 3 The silver ion: Antibacterial mechanism of action The silver ion Ionized silver (Ag+ cation) is one of the most potent antibacterial agents, active at extremely low concentrations (between 0.0000001% and 0.00006%).16,17 This rapid and bactericidal antimicrobial activity at very low concentrations (1.5 μg/ml) is the consequence of a “multi-target” mechanism of action on numerous bacterial sites, thereby minimizing any risk of selection of resistant mutant microorganisms. Silver sulfate Formula • Silver sulfate is a silver complex. • Structural formula: Ag2SO4. • Silver sulfate is a white, amorphous salt presented in the form of a powder. • It is not very soluble in water (less than 5.7 g/l). Release of the silver ion and antibacterial activity • Silver sulfate compound is not very soluble and cannot cross the cell membranes and exert any antibacterial activity. The antibacterial activity only happens following breakdown of the silver salt in contact with the wound exudate (as shown in the diagrams on opposite page). • The Ag+ ion quickly reacts with the bacterial DNA, replacing the hydrogen atoms linking the two nitrogens belonging to two bases that face each other on the molecule chains of the bacterium’s DNA (as shown in the diagrams on this page).16,17 This substitution by silver blocks bacterial duplication and replication. The bacterium is then incapable of reproducing and the synthesis of proteins is blocked. 4 Mechanism of action • In contact with the wound exudate, the silver sulfate breaks down (Ag2S04→2 Ag+ + S042-) and releases the Ag+ ion, while the Carboxymethylcellulose particles become hydrated and swell to form a surface hydrocolloidal gel. • Dissolved in this way, the silver ions are in an ionic form that is the source of their antibacterial activity. TRIACT polymer matrix Unlike many other silver dressings, dressings featuring TRIACT with Silver do not require hydrating with water or saline prior to use, nor are they inactivated by water or saline. The release of Ag+ from the silver sulfate and its bioavailability at the surface of the dressing interface occurs upon contact with exudate. In contact with wound exudate, the CMC particles swell, break free of the polymer matrix, and form a gel. At the same time, silver ions are also released in the dressing. Ag + Ag + Ag + Ag + Ag + Ag + CMC Ag + Ag2 SO4 Ag + Ag + Ag + Ag + Ag + Ag + Ag + Ag + Ag + Ag + 4818-Illustrations-Chimie2-10 5 Products featuring TRIACT Technology with Silver RESTORE Contact Layer, Silver with TRIACT Technology Non-Adherent Dressing, Antimicrobial n Description Restore Contact Layer, Silver is a non-adhesive, non-occlusive, antimicrobial wound contact dressing, composed of a non-occlusive polyester mesh with a polymer matrix containing hydrocolloid particles (carboxymethylcellulose), petrolatum and silver (2.25mg/sq.inch). Method of sterilization: Sterilized by ionizing radiation. n Indications For Use The barrier functions of Restore Contact Layer, Silver may help reduce infection in low to moderate exuding partial and full thickness wounds, including second degree burns, pressure ulcers, venous stasis ulcers, diabetic ulcers, and graft and donor sites. TRIACT Technology • Petrolatum particles • Hydrocolloid particles • Silver sulfate 6 RESTORE Foam Dressing, Silver with TRIACT Technology Antimicrobial, Non-Adhesive with Non-Adherent Contact Layer n Description Restore Foam Dressing, Silver Non-Adhesive is a non-adhesive, non-occlusive, antimicrobial absorbent dressing, composed of 3 layers: • In contact with the wound, a non-occlusive polyester mesh with a polymer matrix containing hydrocolloid particles (carboxymethylcellulose), petrolatum and silver sulfate (3.22mg/sq.inch). • A non sensitizing, absorbent polyurethane foam pad. • A protective, semi-permeable polyurethane backing. • The mesh size allows the exudates to drain into the absorbent foam pad, reducing the risk of maceration. • The TRIACT mesh allows virtually pain-free removal of the dressing and minimizes damage to newly formed tissue. n Indications For Use The barrier functions of Restore Foam Dressing, Silver Non-Adhesive may help reduce infection in moderately to high exuding partial and full thickness wounds, including partial thickness burns, pressure ulcers, venous stasis ulcers, diabetic ulcers, and graft and donor sites. May be used under compression bandages. TRIACT Technology • Petrolatum particles • Hydrocolloid particles • Silver sulfate super-absorbent Layer Vertical absorption of exudate semi-permeable backing Helps protect the surrounding skin from maceration and allows for favorable MVTR n In contact with the wound The TRIACT with Silver interface releases the silver ion in the dressing and directs the exudate through its mesh towards the absorbent foam (flow conduction). The super-absorbent foam is an expanded polyurethane foam with a honeycomb structure that provides high-performance absorption (4300 g / m2 / 24 h) and exudate retention (≤ 50 %) profile under pressure. The semi-permeable backing at the surface enables vaporization of any excess exudate in order to reduce the risk of dressing saturation and maceration to the wound or periwound skin. 7 In vitro studies on the antibacterial efficacy of the TRIACT with Silver interface Introduction The antibacterial activity of the Ag+ ion has been known since the studies conducted by Billroth in 1874, who first demonstrated its antibacterial properties. Since then, numerous studies have validated its ­antibacterial efficacy on the ­microorganisms most commonly involved in the s­ econdary ­infection of wounds. The emergence of strains that are ­multiresistant to antibiotics, ­initially c ­ ontained ­within hospital settings but ­increasingly ­often found in community ­medicine, means that it is necessary to perform ­studies on its activity against these microorganisms. Objective To determine the antibacterial properties of the TRIACT with Silver (Restore Contact Layer, Silver) on the survival of reference ­bacteria colonizing acute and chronic wounds, along with strains resistant to antibiotics, including Methicillin-Resistant Staphylococcus aureus (MRSA). Method Determine the survival curves of the ­different micro­organisms relative to the population ­observed with a control dressing without silver. The ­samples of dressing are inoculated with a bacterial ­suspension of 108 CFU (colonyforming units) and incubated. The number of surviving bacteria is calculated daily up until D7. 8 Results Control Control RESTORE Contact Layer, RESTORE Contact Layer, Silver Silver 10 9 109 Conclusion: Study of the bacterial survival curves reveals the antimicrobial activity of the TRIACT with Silver interface in comparison with the same dressing without silver. From D1 and throughout the duration of the ­study, the reduction in the number of CFU for all the bacterial strains studied is greater than 104, making it possible to conclude that the TRIACT with Silver ­interface demonstrates antibacterial efficacy on the ­microorganisms tested. 108 108 107107 106106 105105 104104 103103 102102 101101 0 0 D2 D3 D3 D4 D4 D7 D0D0 D1D1 D2 D7 Methicillin-resistant Staphilococcus aureus Survival curve (MRSA) (ATCC43300) TRIACT with Silver has shown the following log reductions for these bacteria (the log reduction is achieved within 24 hours and is maintained for a seven day period): 1011 Name of BacteriaLog Reduction 1010 Methicillin resistant staphylococcus aureus Pseudomonas aeruginosa Streptococcus pyogenes 10 Témoin Interface TLC Ag 9 108 107 106 105 104 103 102 Témoin 101 0 D0 D1 D2 Interface TLC Ag D3 D5 D7 Pseudomonas aeruginosa Survival curve (ATCC902) Data on file 108 107 106 105 104 103 102 101 0 D0 D1 D2 D3 D7 Streptococcus pyogenes Survival curve (ATCC 19615) 9 8 (108) 4 (104) 7 (107) Restore Calcium Alginate Dressing, Silver n Description Restore Calcium Alginate Dressing, Silver is a sterile, non woven pad composed of a high G (guluronic acid) calcium alginate, carboxymethylcellulose (CMC) and ionic silver complex (Silver Sodium Hydrogen Zirconium Phosphate). Restore Calcium Alginate Dressing, Silver features superior absorbency and wet strength, which provides several key benefits: • Remains intact even when saturated – allows easy, one-piece dressing removal • Less residue than other dressings – reduces the need for repeated irrigation that might damage new tissue • Absorbs exudate - protects the peri-wound skin while maintaining a moist wound environment n Indications For Use Restore Calcium Alginate Dressing, Silver is indicated for moderate to heavily exuding partial to full thickness wounds including venous stasis ulcers, arterial ulcers, pressure ulcers, diabetic ulcers, trauma wounds, post-operative wounds, and graft and donor sites. n In contact with the wound RESTORE Calcium Alginate Dressing, Silver is more absorbent than the leading alginate dressing. High Wet Strength 28 Absorbency (g/100cm2) In the presence of wound exudate, the dressing releases silver ions. As wound fluid is absorbed the alginate forms a gel, which assists in maintaining a moist environment for optimal wound healing, and allows for intact removal. The silver ions released in the presence of wound exudate in the dressing are an effective antimicrobial agent against a broad spectrum of micro-organisms frequently associated with the bacterial colonization and infection of wounds. Odor reduction results from the antibacterial effect in the dressing. Restore Calcium Alginate Dressing, Silver is an effective barrier to bacterial penetration. 29 24 20 20 16 12 8 4 0 RESTORE Silver Alginate Aquacel Ag RESTORE Calcium Alginate Dressing, Silver has sustained silver release. Silver Release (ppm) v Aquacel Ag v RESTORE Silver Alginate 200 100 0 2 RESTORE 4 12 24 48 Time (Hours) Competitor 10 96 168 In Vitro studies on the antibacterial efficacy of Restore Calcium Alginate Dressing, Silver 107 106 105 104 103 102 Objective To determine the antibacterial properties of Restore Calcium Alginate Dressing, Silver on the survival of reference bacteria commonly colonizing acute and chronic wounds, including strains resistant to antibiotics (MRSA, MRSE, and VRE). Test Method Determine the survival curves of the different micro-organisms relative to the population observed with a control dressing (calcium alginate without silver). The dressings are inoculated with the micro-organism (106 CFU), incubated,then the number of surviving bacteria is calculated at defined intervals. Conclusion: Study of the bacterial survival curves shows the antimicrobial activity of the Restore Calcium Alginate Dressing, Silver in comparison with the calcium alginate dressing without silver (control). From D1 through D7, the reduction in the number of CFU for all the bacterial strains studied is greater than 105, making it possible to conclude that the Restore Calcium Alginate Dressing, Silver demonstrates antibacterial efficacy on the microorganisms tested. Data on file, Report No. P1081R Results Control Control RESTORE Calcium Alginate Dressing, SilverAlginate RESTORE Calcium Dressing, Silver 109 101 0 D0 D1 D2 D3 Candida albicans Survival curve 10 108 10 107 10 106 108 7 107 6 106 105 5 105 10 4 104 10 3 103 102 102 102 101 10 1 101 00 0 104 103 D7 109 109 8 10 D4 D0 D1 D1 D2D2 D3D3 D4D4 D7 D7 D0 Methicillin-resistant Staphilococcus aureus Survival curve (MRSA) D0 D1 D2 D3 D4 Streptococcus pyogenes Survival curve 109 109 10 8 108 107 107 106 106 10 105 4 10 104 103 103 10 102 1 10 101 0 0 5 2 D0 D1 D2 D3 D4 D7 Methicillin-resistant Staphilococcus epidermis Survival curve (MRSA) D0 D1 D2 D3 Escherichia Coli Survival curve 109 109 108 108 107 107 6 10 106 105 105 104 104 3 10 103 102 102 101 101 0 0 D0 D1 D2 D3 D4 D7 Vancomycin Resistant Enterococcus Survival curve (VRE) 11 D4 D7 D7 D0 D1 D2 D3 D4 D7 Psuedomonas aeruginosa Survival curve Frequently Asked Questions Is the use of dressings with silver sulfate an issue with sulpha allergies? Some people are allergic to a family of drugs called the sulfonamides, or sulfa drugs. These are completely different from the silver sulfate molecule found in Restore Contact Layer Dressing, Silver and Restore Foam Dressing, Silver Non-Adhesive. Sulfate has nothing to do with the sulfonamide molecule, other than the two names sound somewhat similar. What type of silver is silver sulfate? Silver sulfate is a salt. Its chemical formula is Ag2SO.4 The antibacterial activity only happens following breakdown of the silver salt in contact with wound exudate. Once in contact with wound exudate, the silver breaks away from the sulfate in the form of a silver ion (Ag+). Why does the IFU reference changing silver dressings every 3-4 days when the dressings have sustained silver release for up to seven days? Common practice seems to be that wounds showing signs of increased bacterial burden are reassessed more frequently than once per week. How does silver affect bacteria? Ionic Silver (Ag+) can affect bacteria in a number of ways: • The silver ion (Ag+) alters the bacterial cell membrane structures, leading to a loss of the cell contents • The silver ion (Ag+) disrupts the function of the intracellular enzyme systems and alters bacterial respiration and nutritional metabolism of the bacterium • The silver ion (Ag+) binds to the base of the bacterial DNA chains and blocks DNA replication 6,7 What is the PPM (parts per million) of silver that is effective? Research suggests that 5-50 PPM of Silver is toxic to most bacteria.15 What is the difference between bactericidal and bacteriostatic, and why is this important? All Restore dressings with silver deliver bactericidal levels of silver, meaning they kill the bacteria. The term bacteriostatic refers to the inhibition of growth and reproduction of bacteria. According to many wound articles and experts, “In antimicrobial activity testing, an active such as silver may be considered bactericidal if it achieves log10 reductions of 3 log10 or greater”.15 12 REFERENCES: 1 Demling RH, Effects of Silver on Wound Management. Wounds. 13(1-Suppl A): 5-15,2001. 2 Hugo W, Russell A., Principles and practice of disinfection, preservation and sterilization. Oxford UK: Blackwell Scientific Publications, 1982; 8-106. 3 Chopra I., The increasing use of silver-based products as antimicrobial agents: a useful development or a cause for concern? Journal of Antimicrobial Chemotherapy 2007, 59: 587 – 590. 4 Lansdown A, Sampson B, Laupattarakasem P, Vuttivirojana A. Silver aids healing in the sterile skin wound: experimental studies in the laboratory rat. British Journal of Dermatology. 137(5):728-735, November 1997. 5 Gamelli R. et al., A Silver-Coated Antimicrobial Barrier Dressing Used Postoperatively on Meshed Autografts: A Dressing Comparison Study. Journal of Burn Care & Research. 28(5):715-719, September/October 2007. 6. Burd A, et al., A comparative study of the cytotoxicity of silver-based dressings in monolayer cell, tissue explant, and animal models. Wound Repair & Regeneration. 15(1):94-104, January/February 2007. 7. Jung, WK, et al., Antibacterial Activity and Mechanism of Action of the Silver Ion in Staphylococcus aureus and Escherichia coli. Applied and Environmental Microbilogy, Vol 74.(7). April 2008. 8. Yin HQ, Langford R, Burrell RE. Comparative evaluation of the antimicrobial activity of Acticoat antimicrobial barrier dressing. J Burn Care Rehabil 1999;20:195-200. 9 Thomas S, McCubbin P. A comparison of the antimicrobial effects of four silver-containing dressings on three organisms. J Wound Care 2003;12:101-7. 10 Thomas S, McCubbin P. An in vitro analysis of the antimicrobial properties of 10 silver-containing dressings. J Wound Care 2003;12:305-8. 11 Lansdown AB Silver I.: its antibacterial properties and mechanisms of action. Silver 2: toxicity in mammals and how its products aid wound repair. J Wound Care 2002;11:125-130 and 173-177. 12 Wright B, Lam K, Hansen D, Burrell R. Wound management in an era of increasing bacterial antibiotic resistance; a role for topical silver treatment. American Journal of Infection Control; 26(6), December 2998, 572-577. 13 Russell A, Hugo W. Antimicrobial activity and action of silver. Prog Med Chem. 1994; 31:351-357. 14 Lazareth I, Meaume S, Sigal-Grinberg MI, Combemale P, Le Guyadec T, Zagnoli A, Perrot J, Sauvadet A, Bohbot S. 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 2008;20: 158-166. 15. Leaper D. Silver dressings: their role in wound management. International Wound Journal: (3)4:282 – 294. 16. Davies CE, et al, Use of 165 ribosomal DNA PCR and denaturing gradient gel electrophoreses for analysis of the microfloras of healing and non healing chronic venous leg ulcers. J Clin Microbiol, 2004. 42(8):p. 3549-57. 17. Ovington LG, The truth about silver. Ostomy and Wound Mgmt, 2004, 50(9A Suppl): p. 1S-10S. Manufactured for Hollister Wound Care LLC 1580 South Milwaukee Avenue Suite 405 Libertyville, IL 60048 1.888.740.8999 Distributed in Canada by Hollister Limited 95 Mary Street Aurora, Ontario L4G 1G3 1.800.263.7400 www.hollisterwoundcare.com Hollisterwoundcare and wave logo are trademarks of Hollister Incorporated. Restore, TRIACT and graphic are trademarks of Hollister Wound Care LLC. Covered under one or more of the following patents: U.S. Patent No. 6,270,792, 6,794,555 and 6,080,420. Made and printed in USA. ©2009 Hollister Wound Care LLC. 910299-808 910678-409