The use of silver sulfadiazine should be discouraged for burn wounds
Silver-containing antibiotics have been applied as standard topical therapy for patients with partial-thickness burns for decades. Silver sulfadiazine (SSD or SD-Ag) in particular is commonly used to manage burns. However, evidence of their effectiveness remains poorly defined. Two recently published systematic reviews [1, 2] suggested the lack of evidence of effectiveness for silver-containing dressings and topical agents in burns.
In the first article, published on British Journal of Surgery , Brölmann et al. have screened all Cochrane systematic reviews  up to June 2011 published by the Cochrane Wounds and Peripheral Vascular Diseases Groups. They identified and reviewed 44 relevant reviews containing 109 evidence based conclusions. Several evidences regarding burns were listed in table 2 of their article, including “Other fibre dressings and antimicrobial (silver) dressings may have no effect on, or even prolong, healing”, “A reduction in burn size at day 5 was seen when TNP (topical negative pressure) was compared with SSD” and “Contradictory limited evidence of increased and decreased infection rates when using SSD cream. No evidence for effectiveness of topical silver for preventing wound infection in terms of wound healing and wound infection”, and they concluded that “For burn wounds the use of silver sulfadiazine should be discouraged, as several trials showed a trend towards wound healing delay and increased pain and infection rates” in their results for acute wounds. Furthermore, they recommended that “In acute wounds do not use silver sulfadiazine as topical agent” in table 8 of their article.
One systematic review  cited by Brölmann summarized the best available evidence from a total of 26 included randomised controlled trials (RCTs) relating to the effects of dressings used to treat adults with superficial or partial thickness burns, and the results indicated that burn wounds dressed with hydrogels, silicon coated dressings, biosynthetic dressings and anti microbial dressings healed more rapidly than those dressed with SSD or chlorhexidine impregnated gauze dressings. Also in this review, there was a finding, not statistically significant in all studies but was consistent for all intervention dressings, that the pain experienced by patients appeared to be reduced with the use of the intervention dressing when compared against SSD or chlorhexidine dressings.
In another systematic review  cited by Brölmann, 26 RCTs (2066 patients) were identified. Due to the heterogeneity of treatments and outcomes precluded meta-analysis, they grouped results according to wound type and silver preparation. The comparisons in terms of infection rate, wound healing rate, pain, and costs showed statistically significant differences in favour of non-silver dressing against SSD with conclusions that “ there was no evidence to support the use of silver sulphadiazine (SSD) for prevention of wound infection in patients with partial-thickness burns. None of the trials indicated a beneficial effect for SSD for other outcomes when compared with other silver-containing or non-silver dressings. Furthermore, there was evidence that SSD may delay wound healing, may be more expensive, and may be more painful when applied to burns.”
In the second systematic review article, published on Burns, Aziz et al. aimed to evaluate the effectiveness of silver containing dressings and topical silver for preventing infection and promoting healing in burns wounds through a meta-analysis of the available evidence. They identified 14 RCTs involving 877 participants. Their results indicated that “topical silver showed significantly worse healing time compared to the non-silver group and showed no evidence of effectiveness in preventing wounds infection”. Their review suggests that “silver-containing dressings and topical silver were either no better or worse than control dressings in preventing wound infection and promoting healing of burn wounds”.
In addition, SSD has toxic effect on skin cells  and tends to adhere to wound surface and requires frequent dressing changes which would hurt newly generated epithelium and delayed wound healing . Irrefutable evidence has shown that silver is absorbed into the systemic circulation and excreted in urine after application of silver-containing pharmaceutical preparation. Study has shown that silver released from SSD was toxic in keratinocyte, hepatocyte, neutrophils, leucocyte and fibroblast and was association with a loss in cellular identity [8, 9]. One of the possible outcome of human keratiocytes is degenerative changes which lead to actual "delay" of wound re-epithelialisation. Furthermore, one consideration has been implicated in bacteria after long time exposure to silver, the consequential bacterial resistance to silver  .
According to the nature of bacteria toward antimicrobial agent, intrinsic and acquired mechanism may emerge as bacteria proliferate under selective pressure. Clinical evidence has found patients who died from infection contained silver resistant strain of bacteria at their burn wound.
A quick search in PubMed for “systematic review on the effectiveness of silver sulphadiazine on burns” retrieved two relevant articles, both of which are not in favor of SSD. The review by Wasiak et al.  got the view of “ likely to be ineffective or harmful” for SSD cream and that “Silver sulfadiazine cream may prolong healing times and increase pain compared with other treatments”. The other article by Andrew et al.  identified only 7 animal studies providing conflicting results.
In summary, since there is no strong clinical evidence supporting the use of SSD in burns and that “The explosion in profits for industry has more often than not been based on high levels of advertising rather than high levels of evidence of effectiveness” , the conclusion “For burn wounds the use of silver sulfadiazine should be discouraged ” and recommendation “In acute wounds do not use silver sulfadiazine as topical agent”, made by Brölmann et al. in their newly published systematic review on British Journal of Surgery, are reliable. Their study helps to illuminate the lack of evidence for silver containing dressings and agents, in particular SSD, for certain types of wound like burns, which may imply that current practice is not evidence-based and needs to change in order to ensure best quality care. As stated by Palfreyman , “Their review will help clinicians and policy-makers to make decisions regarding treatment based on evidence rather than tradition or expert opinion. This can be especially important within the area of wound care where high-quality evidence is often lacking and systematic reviews may be portrayed as merely a means of rationing access and reducing choice”.
TAO Guo-xin, George Shannon
Beijing Rongxiang Institute of Regenerative Medicine, Beijing 100020
The Institute of Applied Science for Human Regeneration and Rejuvenation Andrus Gerontology Center, University of Southern
California, Los Angeles, CA 90089, USA
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