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Silver Sulfadiazine


Silver Sulfadiazine

Article Author:
Rosemary Oaks
Article Editor:
Renford Cindass
Updated:
3/31/2020 9:20:46 AM
For CME on this topic:
Silver Sulfadiazine CME
PubMed Link:
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 a vital factor in the prevention of burn wound infection and thus burn sepsis in these patients. Topical silver sulfadiazine is a common antibacterial prophylaxis agent for burns. The medication is known for its safety and tolerability. Typically burn dressings consists of topical silver sulfadiazine in combination with fine mesh gauze and is usable in both the inpatient and outpatient setting. It is widely available, and it is a low-cost drug, making it a standard choice in the prevention of 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 for the prevention and treatment of 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 for the prevention of 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]

Mechanism of Action

Silver sulfadiazine is a sulfonamide-containing antibacterial; however, unlike other sulfa drugs, this does not inhibit folic acid synthesis. Its antibacterial effects are due to the silver ions. As such, the silver ions only act superficially, and there is limited eschar penetration. 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.[4][5][6][7]

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 do occur. Silver sulfadiazine application should be 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 cover the burned area fully. 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 as important.

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.[8] 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.

Hematologic effects are the most common side effects, which include 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. 

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.

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.[9][10][11]

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 extremely susceptible to sulfonamides. Exposure can result in severe hyperbilirubinemia and possible kernicterus.[12]

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

There are no dosing adjustments for liver or kidney diseases.

Monitoring

No additional monitoring is necessary with the use of silver sulfadiazine. 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 in part because burn injuries can result in extensive loss of free water and, therefore, electrolyte disturbances. 

Some formulations of silver sulfadiazine 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.[13]

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.

Propylene glycol in large amounts 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.[14] 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.[13]

Enhancing Healthcare Team Outcomes

Although generally considered extremely safe, all healthcare providers should be aware of the potential risks associated with the use of silver sulfadiazine. 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 continuing to monitor 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 when it comes to outpatient burn management with silver sulfadiazine. As discussed above, patients may need instruction about proper usage of the medication and ways to ensure safety and effectiveness. The managing physician 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.[15]


References

[1] Williams FN,Herndon DN,Hawkins HK,Lee JO,Cox RA,Kulp GA,Finnerty CC,Chinkes DL,Jeschke MG, The leading causes of death after burn injury in a single pediatric burn center. Critical care (London, England). 2009     [PubMed PMID: 19919684]
[2] Hummel RP,MacMillan BG,Altemeier WA, Topical and systemic antibacterial agents in the treatment of burns. Annals of surgery. 1970 Sep;     [PubMed PMID: 5459095]
[3] Norman G,Christie J,Liu Z,Westby MJ,Jefferies JM,Hudson T,Edwards J,Mohapatra DP,Hassan IA,Dumville JC, Antiseptics for burns. The Cochrane database of systematic reviews. 2017 Jul 12;     [PubMed PMID: 28700086]
[4] Ullah S,Hashmi M,Kharaghani D,Khan MQ,Saito Y,Yamamoto T,Lee J,Kim IS, Antibacterial properties of in situ and surface functionalized impregnation of silver sulfadiazine in polyacrylonitrile nanofiber mats. International journal of nanomedicine. 2019;     [PubMed PMID: 31354260]
[5] Modak SM,Sampath L,Fox CL Jr, Combined topical use of silver sulfadiazine and antibiotics as a possible solution to bacterial resistance in burn wounds. The Journal of burn care     [PubMed PMID: 3146573]
[6] Fox CL Jr,Modak SM, Mechanism of silver sulfadiazine action on burn wound infections. Antimicrobial agents and chemotherapy. 1974 Jun;     [PubMed PMID: 15825409]
[7] Durán N,Durán M,de Jesus MB,Seabra AB,Fávaro WJ,Nakazato G, Silver nanoparticles: A new view on mechanistic aspects on antimicrobial activity. Nanomedicine : nanotechnology, biology, and medicine. 2016 Apr     [PubMed PMID: 26724539]
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[9] Hadrup N,Sharma AK,Loeschner K, Toxicity of silver ions, metallic silver, and silver nanoparticle materials after in vivo dermal and mucosal surface exposure: A review. Regulatory toxicology and pharmacology : RTP. 2018 Oct;     [PubMed PMID: 30125612]
[10] Lockhart SP,Rushworth A,Azmy AA,Raine PA, Topical silver sulphadiazine: side effects and urinary excretion. Burns, including thermal injury. 1983 Sep;     [PubMed PMID: 6640389]
[11] Kulick MI,Wong R,Okarma TB,Falces E,Berkowitz RL, Prospective study of side effects associated with the use of silver sulfadiazine in severely burned patients. Annals of plastic surgery. 1985 May;     [PubMed PMID: 4083697]
[12] "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997 Feb     [PubMed PMID: 9024461]
[13] Zar T,Graeber C,Perazella MA, Recognition, treatment, and prevention of propylene glycol toxicity. Seminars in dialysis. 2007 May-Jun;     [PubMed PMID: 17555487]
[14]     [PubMed PMID: 23386980]
[15] Al-Mousawi AM,Mecott-Rivera GA,Jeschke MG,Herndon DN, Burn teams and burn centers: the importance of a comprehensive team approach to burn care. Clinics in plastic surgery. 2009 Oct;     [PubMed PMID: 19793550]