Reevaluating the Use of Silver Sulfadiazine Cream in the Management of Burns

According to the American Burn Association, about 450,000 serious burn injuries occur in the United States every year that require medical attention.¹ Overall, the goals of treatment are to control pain, remove dead tissue, prevent infection, reduce scarring, and regain function.² Depending on the burn severity, appropriate management may involve initial resuscitation and stabilization, pain management, and wound care, which often involves the use of antimicrobial agents.¹ One antimicrobial agent commonly used in the management of burns is silver sulfadiazine (SSD). Formulated as a 1% topical cream, SSD is FDA-approved as an adjunct for the prevention and treatment of wound sepsis in patients with second- and third-degree burns.³ Anecdotally, though, SSD may have become the agent of choice for all types of burns, including minor burns.⁴ Despite SSD’s popularity, compelling evidence to support its use in the management of burns is lacking. The aim of this article is to provide the reader with an assessment of SSD’s utility for managing burns.

Silver sulfadiazine, which combines silver ions with a sulfonamide moiety, has broad antimicrobial activity. It is bactericidal for many gram-negative and gram-positive bacteria and also has activity against yeast.³ Silver sulfadiazine is considered to be safe, however, dermatologic, gastrointestinal, hematologic, hepatic, neurologic, and renal effects have been reported with its use. The product is contraindicated in patients with severe hypersensitivity reactions following application, pregnant women at or close to term, premature infants, and in infants during the first 2 months of life.³ Although SSD is available as a prescription medication marketed under the brand names Silvadene and Thermazene, it is available generically, as well. The average wholesale price for a 50 g jar of SSD cream is approximately $15.00 and the wholesale acquisition cost is approximately $12.00.⁵

To assess whether clinical evidence supports the use of SSD in the management of burns, we performed a search of PubMed using the terms “silver sulfadiazine” and “burns”. In order to obtain the highest level of evidence, our search was limited to meta-analyses and systematic reviews. Although our search yielded a total of 24 articles, this review focuses on the 5 meta-analyses and systematic reviews wherein the emphasis was on the comparison of SSD with other interventions in the management of burns. The comparative interventions included aloe vera, bacitracin, collagenase, honey, petrolatum, as well as various other preparations/dressings.

Clinical Data

A 2019 systematic review and meta-analysis by Maciel et al. evaluated the efficacy of SSD versus numerous other treatments when used for wound healing in burn patients.⁶ The authors analyzed 11 randomized controlled trials (RCTs) and identified wound-healing time as the primary outcome. The authors concluded that the comparator treatments were statistically superior to SSD with respect to the mean time for complete wound healing.

In a 2018 systematic review and meta-analysis, Nímia et al. examined the efficacy of SSD versus silver-containing and non-silver-containing dressings.⁷ The outcomes that were assessed included time to wound healing and rate of infection. After analyzing 24 RCTs, the authors concluded that dressings with and without silver showed better outcomes than SSD with respect to time to wound healing. Additionally, burns treated with non-silver-containing dressings were less likely to become infected than burns treated with SSD; there were no differences between silver-containing dressings and SSD with respect to this outcome.

A 2017 systematic review and meta-analysis by Aziz et al. examined the effects of honey as compared with SSD in the management of burns.⁸ The primary outcomes included time to complete wound healing and proportion of infected wounds rendered sterile (free from bacteria). The meta-analysis of 9 RCTs found that honey was more effective than SSD in the aforementioned parameters. The authors concluded that although this analysis favored honey over SSD, high quality evidence to support the use of honey in clinical practice is scarce.

A 2016 systematic review by Heyneman et al. analyzed 52 RCTs to evaluate the role of SSD as compared with a variety of burn dressings in the treatment of partial-thickness burns.⁹ The outcome parameters included wound healing, infection, pain, and patient satisfaction. The authors concluded that most viscous, solid, and biological dressings had better healing properties, resulted in less pain, and increased patient satisfaction compared to SSD. With respect to the infection parameter, the efficacy of SSD was comparable to the other dressings. The authors also concluded that since rapid wound closure is essential to obtain optimal functional and aesthetic outcomes, the standard use of SSD in the noninvasive treatment of burn wounds can no longer be supported. 

A 2014 systematic review and meta-analysis by Rashaan et al. assessed 7 RCTs to evaluate the efficacy of SSD as compared to non-silver treatments in the management of partial-thickness burns in children.¹⁰ The outcome measures included wound healing time, number of dressing changes, pain, length of hospital stay, infection, and grafting rates. The authors concluded that non-silver treatment may be preferred over SSD with respect to wound healing time, dressing changes, pain, and length of hospital stay.

Summary

Although SSD is commonly prescribed for the management of burns, numerous systematic reviews and meta-analyses found that overall, SSD was inferior to the various agents that it was compared with. Moreover, SSD seemed to have had a negative impact on some of the outcomes related to wound healing. In view of the above, and as expressly noted in some of the aforementioned reports, the use of SSD as an agent of choice in the management of burns should be discouraged.

Dr Nathan is the director at the International Drug Information Center and associate professor at Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University.

Dr Grossman is a drug information specialist at the International Drug Information Center and adjunct assistant professor at Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University.

References

1. American Burn Association. Advanced burn life support course: Provider manual 2018 update. Published 2018. Accessed December 1, 2020. http://ameriburn.org/wp-content/uploads/2019/08/2018-abls-providermanual.pdf
2. Burns: Diagnosis and treatment. Mayo Clinic. July 28, 2020. Accessed December 1, 2020. https://www.mayoclinic.org/diseases-conditions/burns/diagnosis-treatment/drc-20370545
3. Silvadene. Package insert. Pfizer Inc; 2020. Accessed December 1, 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c437213a-1cd4-445e-a39f-bbcacb9f746f
4. Chung JY, Herbert ME. Myth: silver sulfadiazine is the best treatment for minor burns. West J Med. 2001;175(3):205-206. doi:10.1136/ewjm.175.3.205
5. RED BOOK: IBM Micromedex. Truven Health Analytics/IBM Watson Health; 2020. Accessed December 1, 2020. https://www.ibm.com/products/micromedex-red-book
6. Maciel ABDS, Ortiz JF, Siqueira BS, Zanette GF. Tissue healing efficacy in burn patients treated with 1% silver sulfadiazine versus other treatments: a systematic review and meta-analysis of randomized controlled trials. An Bras Dermatol. 2019;94(2):204-210. doi:10.1590/abd1806-4841.20198321
7. Nímia HH, Carvalho VF, Isaac C, Souza FÁ, Gemperli R, Paggiaro AO. Comparative study of silver sulfadiazine with other materials for healing and infection prevention in burns: A systematic review and meta-analysis. Burns. 2019;45(2):282-292. doi:10.1016/j.burns.2018.05.014
8. Aziz Z, Abdul Rasool Hassan B. The effects of honey compared to silver sulfadiazine for the treatment of burns: A systematic review of randomized controlled trials. Burns. 2017;43(1):50-57. doi:10.1016/j.burns.2016.07.004
9. Heyneman A, Hoeksema H, Vandekerckhove D, Pirayesh A, Monstrey S. The role of silver sulphadiazine in the conservative treatment of partial thickness burn wounds: A systematic review. Burns. 2016;42(7):1377-1386. doi:10.1016/j.burns.2016.03.029
10. Rashaan ZM, Krijnen P, Klamer RR, Schipper IB, Dekkers OM, Breederveld RS. Nonsilver treatment vs. silver sulfadiazine in treatment of partial-thickness burn wounds in children: a systematic review and meta-analysis. Wound Repair Regen. 2014 Jul-Aug;22(4):473-82. doi: 10.1111/wrr.12196