Recent guidelines are disputing the notion that one should use antimicrobial dressings on wounds even when there is no evidence of infection. Accordingly, these authors take a closer look at this subject with a thorough review of the literature and an intriguing case study.
While it is well established that topical antimicrobials play an important, adjunctive role in wound infections, the role of antimicrobial dressings for clinically clean, uninfected wounds remains a topic for debate.1
In May 2012, the Infectious Diseases Society of America (IDSA) published its most recent Clinical Practice Guideline.2 After a thorough review of all pertinent literature, the IDSA panel strongly advocated against using topical antimicrobials for most clinically uninfected wounds. At first glance, it may seem perplexing why leading experts would advise against something as innocuous as prophylaxis against biofilm formation and wound infection with the use of antimicrobial dressings. Let us take a closer look at key considerations for this reasoning.
The top reason for recommending against antimicrobials is likely due to the lack of evidence substantiating the benefit of antimicrobial dressings over conventional wound care therapy.3-9 The research on dressings used in wound care is generally suboptimal. Several recent systematic reviews have suggested that silver-containing dressings and topical silver were neither better nor worse than control dressings in preventing wound infection and promoting healing.10-13
One such review was a 2010 Cochrane Review, which evaluated 26 trials involving 2,066 participants and compared silver-containing dressings against dressings without silver.13 Six of the trials focused on a mixture of different types of wounds while the other 20 trials concentrated on burn wounds. The authors of the review deemed that the trials were of poor quality with the silver dressings having no impact on infection. Furthermore, the review found the silver-containing products increased the healing time of partial-thickness burn wounds.
Although another Cochrane Review noted some evidence to support the use of cadexomer iodine, most of the trials were small and many had methodological problems such as poor baseline comparability between groups, and failure to use (or report) true randomization.14 The use of honey for treating wounds was the subject of a 2008 Cochrane systematic review.15 On the basis of data from research trials that met the inclusion criteria, the authors concluded that honey may reduce the healing time for mild to moderate superficial and partial thickness burns, but did not significantly hasten leg ulcer healing. The systematic review found insufficient evidence to guide clinical practice for other uses.
Most clinical practices mirror these ambiguous findings. Antimicrobial dressings such as silver and cadexomer iodine-impregnated wound products are in common use in daily practice but despite the current wide use of antimicrobial dressings, very few, if any, clinicians can report a 0 percent infection rate or 100 percent healing rate because of the use of antimicrobial dressings.
Can Antimicrobial Dressings Lead To Cytotoxicity?
Another reason for the IDSA advising against the use of topical antimicrobials may be the potential to cause cytotoxicity and local adverse effects. In vitro studies in patients with diabetes found silver dressings to be cytotoxic against fibroblasts by significantly modifying the cell morphology.16 This subsequently caused decreased cell proliferation and decreased collagen synthesis. One cell culture study tested 17 wound care products and found products that contained silver or chlorhexidine to be the most cytotoxic.17
While one may note that these studies were in vitro as opposed to in vivo or clinical experimentation, the fact that antimicrobial dressings demonstrated little clinical efficacy in infection prevention and wound healing makes their use more difficult to justify. After reviewing the evidence, it would be difficult to advocate the use of a product with a lack of clinical evidence and the potential to be cytotoxic. Moreover, the increased use of topical antimicrobials may further promote the emergence of bacterial resistance.18-20 While the currently reported clinical incidence of widespread resistance to silver and other topical antimicrobials remains low, the ubiquitous use of topical antimicrobials warrants the monitoring of silver and/or other antimicrobial resistance in wound care.
Does Reducing Bioburden Bolster Wound Healing?
We also need to address the idea that reducing the “bioburden” of chronic skin wounds with antimicrobial dressings enhances healing in chronic wounds. While there is agreement that virtually all wounds are contaminated with microorganisms, some researchers believe the superficial contamination usually has no clinical consequence as the wounds typically show no evidence of infection and heal as expected.6 Others believe that every foot ulcer requires administration of antibiotics, either for therapy or prophylaxis.21
However, despite reasonable arguments from both sides regarding this controversial topic, available studies and clinical practice guidelines from experts do not support this view.3,6,22 While some experimental animal data and studies with burn wounds and skin grafts support this theory behind antimicrobial prophylaxis, most of the published clinical trials indicate antibiotic therapy does not improve the outcome of uninfected lesions.22-24
For example, in a 2012 article in Advances in Skin and Wound Care, authors compared the efficacy of two different silver impregnated dressings, a sodium carboxymethyl cellulose 1.2% ionic silver dressing and a bovine native collagen/ionic silver dressing, and their impact on wound bioburden and wound closure.27 What the study found was that both silver dressings had similar results in the rate of wound healing and little effect on the actual bioburden present in chronic wounds. In addition, neither dressing demonstrated any significant differences in wound closure rate. Although the study involved only a small sample size, the results showed little effect on wound bioburden, which further rouses the debate of using antimicrobial dressings when one can manage such bioburden efficiently through appropriate debridement of the wound bed.27
In all fairness, the management and reduction of bioburden to facilitate wound healing are plausible. However, until such evidence is available from well-designed, methodologically standardized outcome measurement research, there is limited justification for the use of antimicrobial dressings in a clinically clean, non-infected wound when traditional debridement practices are already well established.
Why The Efficacy Of Antimicrobial Dressings May Not Justify Their Cost
Finally, one must consider the cost of the antimicrobial dressings. Healthcare is already one of the most expensive industries worldwide. The medical device market and wound care market are no exceptions.
In 2012, the U.S. Wound Registry evaluated the average cost of therapy for patients undergoing treatment of wounds in the United States.28 To accomplish this study, researchers looked at five years of data from 59 hospital outpatient wound centers throughout 18 states, which involved 5,240 patients with 7,099 wounds. After accounting for physician fees, procedure costs and cost of operation, researchers found the average cost to heal a wound ranged from $3,927 to $9,358. The study did not involve inpatient costs or the costs of non-healing wounds so the average costs are most likely much higher with the costs of non-healing wounds rising in linear fashion. This once again questions the usefulness of antimicrobial dressings in comparison to their cost.
One example of this is the provocative 2010 article published in the popular British newspaper, The Telegraph, which cited the waste of millions of pounds by British National Health Services (NHS) on silver impregnated dressings amid doubts over their effectiveness.29 The article was based on a large clinical trial comparing silver-containing dressings with non-medicated dressings in venous leg ulcer treatment that found no evidence to justify the use of the more expensive silver dressings in routine, uninfected venous leg ulcer care. The authors of the study concluded that silver dressings offered no real clinical advantage or improvement in wound healing and patient quality of life, but are significantly more expensive.
The article provoked reactions not only within the United Kingdom but internationally as well. Other news media around the world broadcasted the news and patients reportedly refused silver dressings because they read in popular press that silver does not work.
While quality published studies on the cost-effectiveness of antimicrobial dressings are currently lacking, it is well known that antimicrobial wound dressings cost more than those without antimicrobial properties. The antimicrobial dressing segment is a significant portion of the medical device market and consequently, marketing and promotional issues can occasionally obscure the evidence that clinicians need to have in order to make informed decisions about the appropriate treatment for their patients.22 The higher cost associated with antimicrobial dressings does not seem justifiable considering the general lack of clinical evidence.
Case Study: Chronic Wound Healing Without Antimicrobial Dressings
A 54-year-old male presented with a chronic wound at the dorsum of his left foot following incision and drainage secondary to an abscess on the second metatarsophalangeal joint.30
The patient’s past medical history was significant for 12 years of diabetes and hypertension. His vascular status was intact with palpable pedal pulses and immediate capillary filling time to all digits. Protective sensation to both feet was absent via the Semmes-Weinstein monofilament. The dermatologic presentation included a pre-ulcerative lesion at the dorsal aspect of the proximal interphalangeal joint (PIPJ) of the second digit with moderate edema and erythema.
Musculoskeletal examination revealed a semi-rigid contracture at the PIPJ of the second digit. Limited joint mobility was also present in the remaining pedal joints. Radiographs were negative for osteomyelitis.
The patient presented to the office after noticing a red, hot, painful mass on the dorsum of his left foot. He was complaining of constitutional symptoms, was admitted to the hospital and underwent an emergent incision and drainage of the abscess. Postoperatively, he received a total of 20 hyperbaric oxygen treatments (HBOT). The wound care regimen included daily dressings with an enzymatic debriding agent.
Four weeks postoperatively, he received a human fibroblast-derived dermal substitute on the wound base and physicians monitored him for two weeks. To expedite healing in this patient at high risk for infection, physicians applied a bilayered cell therapy (Apligraf, Organogenesis). The patient healed completely within three weeks.
This case study is an example of a wound which, following surgery and local wound care, did not receive an antimicrobial dressing and the patient healed without incident. In this acute wound setting, enzymatic debridement, HBOT and other wound care management helped the patient achieve healing. The clinicians were able to reduce the bioburden and manage the wound appropriately.
In regard to clean, uninfected wounds, there needs to be further investigation into the efficacy of antimicrobial dressings given the lack of robust clinical and laboratory research. There are other treatments such as appropriate debridement to utilize in a clean, uninfected chronic wound to aid in closure. We as clinicians need to expand our armamentarium of available modalities.
Despite the reasons listed above, some clinicians may still have the “why not” mentality and argue that while there is a lack of evidence supporting the benefits of antimicrobial dressings, there is also no evidence citing harmful effects. Some may also argue that the higher cost for antimicrobial dressings is a relatively small price to pay for the possibility of preventing infection and possibly amputation. While the argument may seem sensible, the long-term accruing effect of exposing a wound to antimicrobial dressings on a daily basis has yet to undergo examination.
In addition to the concern about the potential toxicity to healthy cells in wound beds, there is little information on the cumulative systemic absorption of chronic use of antimicrobial agents, especially in wounds with a large surface area. Moreover, as modern healthcare providers who are working with limited financial resources, we need to be practicing the best possible evidenced-based medicine, both to ensure the best care as well as fiscal responsibility.
Regardless of one’s position on either side of the debate, wound care should always begin with ensuring adequate debridement, adequate perfusion, removal of any foreign bodies, pressure mitigation and addressing the underlying metabolic pathology. Guidelines are available to help classify the wound and determine the recommended approach to antimicrobial therapy.
The impact of antimicrobial application on the wound bioburden needs careful examination. The currently available evidence is too weak to recommend any particular antimicrobial dressing.6,31 Large impartial studies are needed on the efficacy and cost-effectiveness of antimicrobial interventions.
With the potential risks of local adverse effects, promotion of bacterial resistance and a lack of evidence of any advantages, most expert consensus panels do not advocate using topical antimicrobials for most clinically uninfected wounds.
Dr. Campbell is a Research Associate for the Center of Lower Extremity Ambulatory Research (CLEAR) at the Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science in Chicago.
Dr. Woodard is an Assistant Professor in the Department of Podiatric Surgery and Applied Biomechanics at the Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science in Chicago. She is a Fellow of the American College of Foot and Ankle Surgeons.
Dr. Wu is the Director of the Center for Lower Extremity Ambulatory (CLEAR) at the Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science in Chicago. She is an Associate Professor for the Center for Stem Cell and Regenerative Medicine at the School of Graduate and Postdoctoral Studies at the Rosalind Franklin University of Medicine and Science. She is also an Associate Professor in the Surgery Department and the Associate Dean of Research at the aforementioned Scholl College of Podiatric Medicine.
1. Arzt H, Fromantin I, Ribinik P, et al. Which medical device and/or which local treatment are to be used, as of 2012, in patients with infected pressure sore? Developing French guidelines for clinical practice. Ann Phys Rehabil Med. 2012; 55(7):498-507.
2. Lipsky BA, Berendt AR, Cornia PB, et al. Executive summary: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012; 54(12):1679-84.
3. Lipsky BA, Hoey C. Topical antimicrobial therapy for treating chronic wounds. Clin Infect Dis. 2009; 49(10):1541-9.
4. Hinchliffe RJ, Valk GD, Apelqvist J, et al. A systematic review of the effectiveness of interventions to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Metab Res Rev. 2008; 24(Suppl 1):S119-44.
5. Hilton JR, Williams DT, Beuker B, et al. Wound dressings in diabetic foot disease. Clin Infect Dis. 2004; 39(Suppl 2):S100-3.
6. Nelson EA, O’Meara S, Golder S, et al. Systematic review of antimicrobial treatments for diabetic foot ulcers. Diabet Med. 2006; 23(4):348-59.
7. Trial C, Darbas H, Lavigne JP, et al. Assessment of the antimicrobial effectiveness of a new silver alginate wound dressing: a RCT. J Wound Care. 2010; 19(1):20-6.
8. Toy LW, Macera L. Evidence-based review of silver dressing use on chronic wounds. J Am Acad Nurse Pract. 2011; 23(4):183-92.
9. Lund-Nielsen B, Adamsen L, Kolmos HJ, et al. The effect of honey-coated bandages compared with silver-coated bandages on treatment of malignant wounds-a randomized study. Wound Repair Regen. 2011; 19(6):664-70.
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12. Storm-Versloot MN, Vos CG, Ubbink DT, Vermeulen H. Topical silver for preventing wound infection. Cochrane Database Syst Rev. 2010; 17(3):CD006478.
13. Bergin SM, Wraight P. Silver based wound dressings and topical agents for treating diabetic foot ulcers. Cochrane Database Syst Rev. 2006; 25(1):CD005082.
14. O’Meara S, Al-Kurdi D, Ologun Y, Ovington LG. Antibiotics and antiseptics for venous leg ulcers. Cochrane Database Syst Rev. 2010; 20(1)CD003557.
15. Jull AB, Rodgers A, Walker N. Honey as a topical treatment for wounds. Cochrane Database Syst Rev. 2008; 8(4):CD005083.
16. Zou SB, Yoon WY, Han SK, et al. Cytotoxicity of silver dressings on diabetic fibroblasts. Int Wound J. 2012; 10(3):306-12.
17. Kempf M, Kimble RM, Cuttle L. Cytotoxicity testing of burn wound dressings, ointments and creams: a method using polycarbonate cell culture inserts on a cell culture system. Burns. 2011; 37(6):994-1000.
18. Atiyeh BS, Hayek SN. The safety and efficacy of dressings with silver - addressing clinical concerns. Int Wound J. 2007; 4(3):283-4.
19. Chopra I. The increasing use of silver-based products as antimicrobial agents: a useful development or a cause for concern? J Antimicrob Chemother. 2007; 59(4):587-90.
20. Percival SL, Woods E, Nutkepor N, et al. Prevalence of silver resistance in bacteria isolated from diabetic foot ulcers and efficacy of silver-containing wound dressings. Ostomy Wound Manage. 2008; 54(3):30-40.
21. White RJ, Cutting K, Kingsley A. Topical antimicrobials in the control of wound bioburden. Ostomy Wound Manage. 2006; 52(8):26-58.
22. Chantelau E, Tanudjaja T, Altenhofer F, et al. Antibiotic treatment for uncomplicated neuropathic forefoot ulcers in diabetes: a controlled trial. Diabet Med. 1996; 13(2):156-9.
23. Robson MC, Mannari RJ, Smith PD, Payne WG. Maintenance of wound bacterial balance. Am J Surg. 1999; 178(5):399-402.
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29. NHS wastes millions on silver wound dressings ‘that kill infections’. Telegraph. Available at http://www.telegraph.co.uk/health/healthnews/7591908/NHS-wastes-millions... . Published April 15, 2010. Accessed Oct. 30, 2013.
30. Lafontaine J, Michel R. Healing a chronic wound in an immunocompromised patient. Poster, Symposium on Advanced Wound Care (SAWC), San Antonio, 2006.
Beam JW. Topical silver for infected wounds. J Athl Train. 2009; 44(5):531-3.
Editor’s note: For further reading, see “Current Concepts In Wound Bed Preparation” in the August 2011 issue of Podiatry Today, “How To Detect And Treat Infected Wounds” in the July 2004 issue, “A Guide To Selecting The Right Dressings For Wounds” in the July 2013 issue or “Keys To Managing Postoperative Wound Infections” in the August 2013 issue.
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