Silver sulfadiazine: adored by some, detested by others.

10 February, 2019

Silver sulfadiazine cream (better known by its commercial names) remains, since the 70s, in the top of products used in wound healing, predominantly in superficial burns. It seems that the opinion of professionals on this product is divided into two camps: supporters and detractors. Although it is a product that I do not use in my clinical practice, its presence in various presentations during the Journées Cicatrisations 2019 has encouraged to dedicate a post to it:)

What is silver sulfadiazine?

Silver sulfadiazine is a combination of silver nitrate and sulfadiazine, so its bacterial effects are due to the action of these two active principles.

We have already dedicated a post to silver (“Silver in skin wounds”). Sulfadiazine is a type of sulfamide, known traditional broad-spectrum antibacterial (Gram +, Gram – including Pseudomonas, anaerobes). This chemical has a bacteriostatic action, i.e. it prevents the reproduction of bacteria by interfering with their folic acid synthesis. Therefore, when combined in a cream, the bacteriostatic power of sulfadiazine and the silver bactericide effect act in synergy. In short, it is a mixture of a topical antibiotic with silver. Its usual presentation is cream, at a concentration of 1%. The general recommendation is to apply it daily after cleansing the wound to avoid the formation of a pseudo-scab.

I imagine that many of you will already have the following question in your head…

But is it advisable to apply topical antibiotics on wounds?

Although they are commonly used in acute and chronic wounds, the available evidence does not allow us to recommend them. In fact, in clean acute wounds, such as those secondary to dermatological procedures, although the use of topical antibiotics is not indicated, it is a very widespread practice (see post: “How do we manage clean wounds produced after dermatological procedures?“). In chronic wounds, in addition to not having a clear effect on bacteria organized and protected in biofilms, they can produce bacterial resistance and trigger allergic reactions. Returning to the specific topic of silver sulfadiazine, harmful effects on healing have been shown in vitro and in vivo, such as altered activation of macrophages and cytotoxicity on keratinocytes and fibroblasts.¹ Allergic contact dermatitis from silver sulfadiazine, either by allergic reaction to silver or sulfadiazine, is not uncommon.² If a wound worsens after starting treatment with silver sulfadiazine, with increased pain, exudate, and perilesional redness, it may be clinically suspected. This adverse effect is confirmed by epicutaneous tests (patch test). Nitrofurazone is another topical antibiotic widely used in burns and other wounds, which dermatologists know well because it is also responsible for many hypersensitivity reactions.

In order to avoid the possible effects of systemic absorption of silver sulfadiazine, it is necessary to avoid its application in very extensive wounds during prolonged periods of time, especially in patients with renal or hepatic insufficiency. In addition to the potential accumulation of silver in different organs, sulfadiazine could produce blood alterations such as methemoglobinemia, haemolysis, leukopenia or hyperbilirubinemia. With the use of silver sulfadiazine severe cutaneous drug reactions have also been described, such as Stevens-Johnson syndrome.³ However, these adverse effects are considered rare, so silver sulfadiazine is considered a safe drug.

What do the studies conclude?

Most studies are conducted on splitl-thickness burns. However, before we focus on this group of patients, let´s see what has been published on silver sulfadiazine in venous ulcers, as there are many professionals who use it with this indication.

Two prospective series, with 64 and 70 outpatients each (in German and French respectively),³ analyse the number of patients with complete healing at 6 weeks of weekly application of silver sulfadiazine cream. These series found complete healing in 52 and 40 patients respectively, with loss of follow up of 7 patients in this second group. With regard to signs of infection, in the first study they were not detected. In the second study, while 29 patients presented infection data on the day treatment began, only 2 had these signs at 6 weeks. However, a randomized clinical trial with 86 patients with venous ulcers in which silver sulfadiazine is compared to placebo does not show significant differences in complete healing in the two groups.³

Now let’s focus on superficial burns, undoubtedly its most widespread indication. First of all, it must be stressed that the available evidence is scarce and of low quality. In animal models, with rats and pigs, experimental studies have been carried out to compare the benefit of silver sulfadiazine versus placebo (including paraffin gauze, gauze with saline serum, oily excipient without active principle) for the outcome variables “infection” or “complete healing”, with variable results.³

In humans, on the contrary, clinical trials essentially compare silver sulfadiazine cream with other products, as they consider the former as the standard of treatment and normally use it in the control group. Let’s see what these studies conclude in superficial burns in relatively small areas.

Non-occlusive petrolatum gel vs. silver sulfadiazine covered with gauze: a randomized clinical trial compares these two strategies, with daily cures, in two groups of 19 patients each. No significant differences were found in time to complete healing, infection or dermatitis signs.⁴
Silver sulfadiazine vs. paraffin gauze: one study included 15 superficial burns, dividing each wound into an upper half treated with paraffin gauze and the lower half with silver sulfadiazine. Paraffin gauze was changed every 5 days, while silver sulfadiazine was applied daily and also covered with paraffin gauze. Healing of the area treated only with paraffin gauze was faster.⁵
Silver sulfadiazine vs. hydrocolloid dressing: a randomized clinical trial included 50 patients. Burns in the hydrocolloid dressing group required fewer dressing changes and showed faster complete epithelialization with better appearance and pigmentation of the scar area. Patients reported less limitation in their usual activities and greater adherence to hydrocolloid treatment, benefits that add up to lower treatment costs.⁶
Silver sulfadiazine vs. honey: there is growing interest in the use of honey in healing, due to its potential debridement, anti-inflammatory and antibacterial activity. A recent systematic review⁷ includes 9 clinical trials comparing the use of honey and silver sulfadiazine in superficial burns. This study finds faster complete healing and a higher percentage of infection resolution in honey-treated wounds. However, it should be noted that these are small studies (between 27 and 110 patients included) very heterogeneous, with different age groups, variable outcome measures and duration of follow up.⁷
Silver sulfadiazine vs. polyhexanide/betaine gel: polyhexanide/betaine gel has a great interest in wound healing due to its antibacterial and moisturizing action. A randomized clinical trial involving 46 patients found no significant differences in time to complete healing, infection and costs between the group treated daily with silver sulfadiazine and that of polyhexanide/betaine.⁸

What do the position documents and clinical guidelines say?

As we have just seen, although the available studies are few, small in size, and heterogeneous in design, most show the absence of differences or even superiority of other treatments over silver sulfadiazine for superficial burns, in terms of infection and complete healing.⁹ However, if we do a quick search for position documents and clinical practice guidelines, we will find the widespread recommendation for the use of silver sulfadiazine cream in split- thickness burns. In the guideline published by the Japanese Burn Society in 2016,¹⁰ as well as in other clinical guidelines, it is underlined that its recommendation for use is made despite the absence of a good level of evidence.

What is your experience with silver sulfadiazine cream?