Study finds silver sulfadiazine to be far from gold-standard

Silver sulfadiazine (SSD) has long been considered the gold standard for treating wounds, especially burns. A new study, however, strongly refutes SSD’s reputation-indeed, one of the study authors recommends that physicians stop using it.

The study, conducted by researchers from the Albert Einstein College of Medicine in Bronx, N.Y., acknowledges that, as an anti-microbial agent, SSD can prevent infection and accelerate wound healing by lowering bacterial burden. The authors also acknowledge that the study involved mice, and that “the translatability of murine data to humans is questionable.” On the other hand, the authors note, several previous studies have shown that SSD performs less than spectacularly when compared with other wound-healing adjuvants. With all that in mind, the researchers set out to determine SSD’s impact on wound healing and suggest mechanisms by which the activity occurs.

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They began by inducing two 5 mm burns on the backs of mice, which were then split into two groups: untreated control and SSD-treated. Daily photographs and special computer software were used to assess changes in the wound area. Mice were sacrificed for histology on days three, seven and 15. Histologic samples were stained to visualize morphology, collagen deposition, macrophages and neutrophils. Burn wounds were harvested for cytokine analysis and tissue samples were analyzed in duplicate for cytokine expression. Cytokine-signal intensity was determined using special software.

The researchers found that compared with controls, topical SSD applied to burns significantly delayed wound closure. By day three, controls and SSD-treated wounds expanded as compared to the first day-though the extent was significantly greater in the SSD-treated group (49.7 percent versus 23.8 percent). By day 10, the SSD-treated group demonstrated 16.3 percent closure compared with 42.1 closure in controls.

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“Our data suggest a mechanism by which SSD impairs wound healing,” the authors write. “We hypothesize that SSD alters gene expression of IL-1-family genes, resulting in impaired downstream cytokine production and, ultimately, delayed wound healing. In summary, these data suggest a causal relationship by which SSD retards wound healing, though further investigations are necessary.”

NEXT: How study came about

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According to study co-author Adam Friedman, M.D., director of dermatologic research at Albert Einstein College of Medicine, the idea for the study was born in the midst of other research.

“Like so often in science, this study came about by chance observation,” he tells Dermatology Times. “I am investigating several new nanotechnologies I co-developed as potential topical treatments for various wounds-incision, burn and so forth. For the burn model studies, we used SSD as a positive control, as it is the ‘gold standard’ to which new treatments can be compared. Time and again, not only did the nanoparticle treatment impart a better impact on the burn wounds, but the untreated controls did better than SSD as well.”

Dr. Friedman says his team also compared SSD with biafine as part of another project to identify the mechanism by which biafine accelerates wound closure. “Once again, SSD was inferior to all groups, including untreated controls,” he says.

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Given the findings of this study and others, why is SSD still viewed as the gold standard wound-healing treatment?

“The recommendation is archaic at best,” Dr. Friedman says. “I think the most important take-home point [of our study] is this: Stop using SSD. By identifying a potential biological mechanism through which SSD retards burn-wound healing, we not only support the previous clinical observations by giving them a bit more substance, but now have an opportunity to reinvigorate and revitalize the educational and training element, which is to redefine how we as clinicians approach burn treatment. There is clearly a practice gap which needs to be corrected.”

The study was published online in the Journal of Investigative Dermatology. The authors report no conflicts of interest.