Silver has become one of the most commonly used alternatives to topical antibiotics in recent years because of the growing concern over antibiotic resistance. Silver offers a multifaceted antimicrobial approach that makes it less likely for resistance to develop. With its limited and uncommon cytotoxicity, silver can be used to treat infected wounds over time and prevent further complications.

Impact of Infection on Wound Healing

Infections inevitably have a huge impact on the wound healing process, cost, and time. Infections can double the length of stay for patients with wounds,¹ and this additionally increases the patient’s risk of further infection, medication complications, and pressure ulcers.² To prevent secondary complications in patients, health care professionals must consider optimal ways to prevent and treat wound infection. Wound infection depletes micronutrients and oxygen while producing toxins,³ thus delaying wound closure. This delay not only increases the cost of wound management but also escalates the risk for deeper infection or sepsis.⁴ In the case of diabetic foot ulcers, the healing process is already hindered by the mechanisms of diabetes mellitus,⁵ and it is especially important to close the wound as quickly as possible.

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If wounds are not closed in an appropriate amount of time, especially in the case of diabetic patients, the patient may be at risk of deep infection, leading to amputation.⁶ Even if amputation is avoided, infected wounds are at higher risk of becoming chronic. Chronic wounds decrease the quality of life for patients and increase the cost of treatment by nearly 10-fold.⁷ Effective prevention and management of wound infection are essential to improve the quality of life for patients and to reduce overall treatment costs.

Mechanisms of Silver as an Antibacterial

The exact mechanism of silver as an antibacterial agent is under investigation, but current theories propose a multifaceted approach. Silver has seven proposed actions that aid its antibacterial properties. These are:

1. Disruption of the cell wall when in the silver ion form (Ag+)
2. Disruption of the cell membrane through reactive oxygen species
3. Denaturation of ribosomes to inhibit protein synthesis
4. Interruption of adenosine triphosphate production
5. Disruption of DNA replication
6. Denaturation of the cell membrane when silver nanoparticles collect in the cell wall
7. Perforation of the cell membrane as silver nanoparticles

Silver operates through most or all of these mechanisms to provide a comprehensive antimicrobial action.⁸

Guidelines for the Use of Silver Wound Dressings

The literature supports the use of silver for all infected, open wounds, and burns.³ Silver acts both to penetrate any existing biofilm and to destroy the microbes contained within. Silver can be used in nanocrystalline form to offer sustained release so that as the biofilm is disrupted, the silver is able to impede the microbes as they become susceptible.³ Overall, silver use in wound dressings has a low risk for systemic toxicity. The main result of systematic silver use is argyria. This condition, most commonly an outcome of injection or ingestion, appears as silver deposits in the tissue that cause the skin and eyes to take on a gray tint. Argyria can also cause loss of night vision.³

Local toxicity is more common. Silver is cytotoxic to keratinocytes and fibroblasts, which are essential components of the healing process. However, this cytotoxicity most likely does not begin until the concentration of silver is above 60 ppm. The therapeutic range for silver to exhibit antibacterial properties is at least 30-40 ppm. Therefore, experts recommend a therapeutic range of greater than 30 ppm but no more than 60 ppm silver ion concentration and sustaining this concentration for several days to avoid the development of silver resistance.³

Conclusion

The reduction of topical antibiotics use is essential in the fight against antibiotic resistance. When used appropriately, silver has the potential to replace topical antibiotics for certain wound care situations. Therefore, it is important that health care professionals stay up to date on the guidelines for silver use in wound care to promote optimal wound healing for their patients.

References

1. Kusachi S, Kashimura N, Konishi T, et al. Length of stay and cost for surgical site infection after abdominal and cardiac surgery in Japanese hospitals: multi-center surveillance. Surgical infect. 2012;13(4):257-265.

2. Hauck K, Zhao X. How dangerous is a day in hospital? A model of adverse events and length of stay for medical inpatients. Med Care. 2011;49(12):1068-1075. http://www.jstor.org/stable/23053852

3. Khansa I, Schoenbrunner AR, Kraft CT, Janis JE. Silver in wound care-friend or foe?: A comprehensive review. Plast Reconstr Surg Glob Open. 2019;7(8):e2390. doi:10.1097/GOX.0000000000002390

4. Jenkinson RJ, Kiss A, Johnson S, Stephen DJ, Kreder HJ. Delayed wound closure increases deep-infection rate associated with lower-grade open fractures: a propensity-matched cohort study. J Bone Joint Surg Am. 2014;96(5):380-386. doi:10.2106/JBJS.L.00545

5. Patel S, Srivastava S, Singh MR, Singh D. Mechanistic insight into diabetic wounds: pathogenesis, molecular targets and treatment strategies to pace wound healing. Biomed Pharmacother. 2019;112:108615. doi:http://dx.doi.org/10.1016/j.biopha.2019.108615

6. Aziz ARA, Alsabek MB. Diabetic foot and disaster; risk factors for amputation during the Syrian crisis. J Diabetes Complications. 2020;34(2). doi:http://dx.doi.org/10.1016/j.jdiacomp.2019.107493

7. Sen CK. Human wounds and its burden: an updated compendium of estimates. Adv Wound Care (New Rochelle). 2019;8(2):39-48. doi:10.1089/wound.2019.0946

8. Yin IX, Zhang J, Zhao IS, Mei ML, Li Q, Chu CH. The antibacterial mechanism of silver nanoparticles and its application in dentistry. Int J Nanomedicine. 2020;15:2555-2562. doi:10.2147/IJN.S246764