Continuing Education Activity

Silver sulfadiazine is a medication used to prevent, manage, and treat burn wound infections. It is a heavy metal topical agent with antibacterial properties. This activity reviews the indications, action, and contraindications for silver sulfadiazine as a valuable agent in preventing infection in burn patients. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the healthcare team in the care of patients with second and third-degree burns.

Objectives:

• Identify the mechanism of action of silver sulfadiazine.
• Describe the adverse effects of silver sulfadiazine.
• Review the appropriate monitoring of silver sulfadiazine.
• Summarize the importance of improving care coordination amongst interprofessional team members to improve outcomes for burn patients being treated with silver sulfadiazine.

Indications

Burn sepsis is the number one cause of death in patients with extensive burns.[1] Prevention is imperative, and topical antiseptic/antibiotic medications are vital in preventing burn wound infection and thus burn sepsis in these patients. Topical silver sulfadiazine is a common antibacterial prophylaxis agent for burns. The drug is known for its safety and tolerability. Typically burn dressings consist of topical silver sulfadiazine combined with fine mesh gauze and are usable in both the inpatient and outpatient settings. It is widely available and a low-cost drug, making it a common choice to prevent infection in patients with burns.[2]

Because of the threat of disease, topical antibacterial therapy is an important part of wound care in burn patients. Silver sulfadiazine is a sulfa-derived antibiotic medication approved by the Federal Drug Administration to prevent and treat wound infection in patients with 2nd and 3rd-degree burns. The drug was approved for this use in 1973 and has been at the forefront of burn treatment since that time. Clinicians sometimes use this drug is sometimes used in the treatment of other skin infections not related to burns, such as ulcers. These uses do not have approval by the Federal Drug Administration and are “off-label.”

Medical professionals recommend its use once or twice daily, with reapplication as needed to prevent wound-sepsis in the treatment of burns. Topical antibacterial prophylaxis intends to control microbe colonization in the wound and prevent the development of wound-sepsis while also maintaining a low level of systemic absorption. Silver sulfadiazine is the most commonly used topical antibiotic medication in burn patients because of its affordability, ease of use, and tolerability.

Silver sulfadiazine is a broad-spectrum bactericidal antimicrobial effective against gram-positive and gram-negative bacteria, as well as some yeasts. Of note, it is active against Pseudomonas aeruginosa, a common cause of infection in burn patients.[3] However, some research finds data supporting silver-releasing compounds to be equivocal and questions the quality of previous clinical trials, and other topical antibiotics may be more effective.[4]

Mechanism of Action

Silver sulfadiazine is a sulfonamide-containing antibacterial; however, this does not inhibit folic acid synthesis, unlike other sulfa drugs.[5] Its antibacterial effects are due to the silver ions. As such, the silver ions only act superficially, and there is limited eschar penetration.[6] The exact mechanism of action of silver sulfadiazine is currently unknown, but the drug hypothetically produces its bactericidal effects by increasing cell wall permeability through the impairment of DNA replication, the direct modification of the lipid cell membrane, and/or the formation of free radicals.[7][8]

Administration

Only topical formulations have approval for use by the FDA. Most formulations contain 1% silver sulfadiazine. Care is necessary to avoid the periocular region and mucosal surfaces when applying the medication, as research has shown that eye irritation and mucosal absorption can occur. Silver sulfadiazine application should be performed with sterile equipment and minimal trauma to the tissue. This technique is best achieved by using sterile gloves and applying the medication manually. A layer 1/16" should be applied to entirely cover the cleaned, debrided burned area. 

It is important to employ a sterile technique and never "double-dip" when using sterile tongue blades or sterile cotton swabs for smaller burns. Bacteria can be introduced into the tub of medication if not following these guidelines. For a similar reason, each tube or tub of medication should be designated for one patient only to avoid spreading pathogens between patients. Patient education regarding the proper application and use of drugs is imperative, and documentation of that teaching is equally important.

The same administration is used in pediatric burn wounds, although pediatric use is currently off-label as of this writing.

Adverse Effects

Silver sulfadiazine is considered to be extremely safe; however, there should be limitations to its use. This medication slows re-epithelization and should stop once there is visible evidence of healing.[9] Additionally, with repeated use, a pseudoeschar will form over the affected area preventing adequate assessment of the burn wound. This technique requires mechanical debridement to remove, which is often painful.[10][4]

Hematologic effects are the most common side effects, including agranulocytosis, aplastic anemia, hemolytic anemia, and leukopenia. Practitioners should follow laboratory screening recommendations and inquire about symptoms of infection and or anemia during patient encounters.[11]

Dermatologic reactions, including erythema multiforme, pruritis, skin discoloration, skin photosensitivity, rash, and Stevens-Johnson syndrome, have all been reported. Patients who have previously experienced a rash in response to silver sulfadiazine should not use this medication as this can be a sign of an allergy.[12]

It is unknown whether patients with sulfonamide allergies are at risk for cross-reaction to silver sulfadiazine, but product labeling indicates that those patients should avoid use if their previous reaction to sulfonamides has been severe.[13]

Contraindications

Persons with previous hypersensitivity reactions following application, pregnant women, and infants less than two months of age should refrain from using silver sulfadiazine.

Although animal studies did not show any adverse effects in reproduction studies, it is known that systemic absorption does occur with the widespread use of the medication. Therefore there is a theoretical risk of hyperbilirubinemia and kernicterus when using this medication in pregnant women or infants. Infants have an immature glucuronidation mechanism and are therefore highly susceptible to sulfonamides. Exposure can result in severe hyperbilirubinemia and possible kernicterus.[14]

Silver sulfadiazine can be used cautiously in those with glucose-6-phosphate dehydrogenase deficiency, as they are susceptible to hemolysis following exposure to sulfonamide derivatives. Monitoring for anemia and elevated bilirubin may be especially crucial in this patient population.

There are no dosing adjustments necessary for liver or kidney diseases.

Monitoring

No additional monitoring is necessary with the use of silver sulfadiazine in otherwise healthy patients. Electrolytes, serial urinalyses, renal function studies, and complete blood counts require monitoring in those patients with extensive burns, which will require intensive care. This monitoring is partly because burn injuries can result in extensive loss of free water and, therefore, electrolyte disturbances. 

Some silver sulfadiazine formulations contain propylene glycol, which can undergo absorption and reportedly causes serum osmolality disturbances. Serum propylene glycol levels may be obtained as well in certain situations.[15]

Toxicity

Silver sulfadiazine is considered extremely safe, and overdose is uncommon; however, it is essential to remember that systemic absorption of the medication can occur and may be significant, especially when used near mucosal or ocular areas or when used on a large surface area.

In large amounts, propylene glycol is potentially toxic and, as mentioned previously, is found in many formulations of silver sulfadiazine. Toxicity with these formulations has correlated with hyperosmolality, seizures, lactic acidosis, and respiratory depression.[16] Some researchers have found correlations between serum propylene glycol levels and osmolality changes, but these changes were attributed to a combination of medication usage and the physiologic changes of a severely burned state.[15]

Enhancing Healthcare Team Outcomes

As is the case with any medication, an interprofessional team approach is the best way to use silver sulfadiazine therapy. Although generally considered extremely safe, all healthcare providers should be aware of the potential risks associated with silver sulfadiazine use. Providers should encourage patients to use the medication as directed and report any reactions to medication use, including dermatologic reactions. Providers should routinely inquire about symptoms of dermatologic sensitivity and anemia while monitoring patient status with physical exams and laboratory analysis.

Nursing staff plays a vital role in monitoring patient status, especially on an inpatient basis, and are often the first to identify potential adverse effects of medical treatment. Pharmacists can play an equally important role in patient education regarding outpatient burn management with silver sulfadiazine and provide additional instruction on how to use the medication at home since, as discussed above, patients may need instruction about proper medication usage and ways to ensure safety and effectiveness. The managing clinician is ultimately responsible for overseeing the care of the patient. To protect patient safety, the healthcare team should collaborate and maintain open communication about patient status; this type of interprofessional approach will yield improved patient outcomes while minimizing adverse events and treatment failure.[17] [Level 5]