Silver-based topical antimicrobials and dressings

Overview

Silver has been used to treat burn wounds for more than a century, and since the mid-1960s three silver-delivery systems have dominated clinical practice: silver nitrate solution, silver sulfadiazine cream (SSD), and nanocrystalline silver dressings ^[1]. In 1965, Moyer revived interest in silver nitrate solution after in vitro and in vivo work showing that a 0.5% solution was the lowest concentration giving reliable antibacterial action against Staphylococcus aureus, hemolytic streptococci, Pseudomonas aeruginosa, and Escherichia coli ^[1]. Mafenide acetate and silver sulfadiazine appeared shortly after, and silver sulfadiazine became the most widely used topical agent in burn care ^[1]. The dressings have changed; the clinical problem has not. These agents are used because burn wound sepsis kills patients, and over 75% of all burn deaths after initial resuscitation result from infection ^[4].

The modern question is not whether to use silver. It is which silver delivery system, on which wound, and for how long. Silver sulfadiazine became standard therapy for the conservative treatment of partial thickness burns for more than 40 years ^[3]. In the last decade, the evidence base has shifted. Meta-analyses show that nanocrystalline silver dressings reduce length of stay, dressing changes, and surgical interventions compared with silver sulfadiazine ^[5]. New silver dressings and non-silver dressings show faster wound healing than silver sulfadiazine across pooled trials ^[6]. The rate of burn wound infection rises with silver sulfadiazine compared with modern dressings and skin substitutes ^[36]. Silver sulfadiazine is no longer the only defensible default, but it remains widely used because it is cheap, familiar, and broadly effective.

Epidemiology

Partial thickness burns up to 10% TBSA in children are common injuries primarily treated in the outpatient setting using silver-containing dressings ^[25]. Silver-based dressings are the backbone of non-surgical burn wound management across North America, Europe, and Australia. The Cochrane review of antiseptics for burns identified 56 randomized trials enrolling 5,807 participants in this space, most of them comparing a silver-based antiseptic against silver sulfadiazine or another topical antimicrobial, and most of them enrolling adults with second-degree burns under 40% TBSA ^[4]. A retrospective at one referral center followed 157 consecutive patients treated with cerium nitrate-silver sulfadiazine cream over four years, with a median TBSA of 8.5% and inhalation injury in 9.9% ^[11]. Silver dressings reach across every level of the burn system, from outpatient superficial burns to ICU-managed large TBSA injuries awaiting excision.

Pathophysiology

Silver is a broad-spectrum antimicrobial cation. The efficacy of silver sulfadiazine results from its slow and steady reaction with serum and other sodium chloride-containing body fluids, which permits the slow and sustained delivery of silver ions into the wound environment ^[2]. In the original mechanistic work by Fox and Modak, silver, but not sulfadiazine, was bound by bacteria; sulfadiazine did not act as an antibacterial agent in low concentrations but showed specific synergism in combination with subinhibitory levels of silver sulfadiazine ^[2]. A relatively minute amount of sulfadiazine appears active under these conditions ^[2]. This slow-release model explains why older silver formulations are rapidly inactivated by the wound environment and require frequent replenishment ^[18].

Nanocrystalline silver dressings were engineered to overcome that limitation. Introduced in the late 1990s, Acticoat provides sustained release of silver up to 7 days ^[46]. Nanocrystalline silver has rapid and sustained bactericidal activity, and because of this may reduce inflammation and promote healing ^[18]. Kill kinetics testing against common burn wound fungal pathogens found that a nanocrystalline silver-coated dressing provided the fastest and broadest-spectrum fungicidal activity among mafenide acetate, silver nitrate, silver sulfadiazine, and the nanocrystalline product ^[40]. Despite extensive testing and clinical experience, no evidence has emerged of resistance or cytotoxicity to nanocrystalline silver in the original review work ^[18], though more recent in vitro data complicate that claim and are discussed under Complications and Controversies.

The mechanism of the adverse-effect profile follows the same ionic pathway. Silver absorbed through damaged skin reaches the systemic circulation. In burn patients treated with silver sulfadiazine cream, plasma silver concentrations can reach 50 μg/L within 6 hours of treatment and a maximum of 310 μg/L ^[7]. Silver in urine is detectable after one day of treatment and may reach a maximum of 400 μg/day ^[7]. After absorption, silver deposits in tissues, including skin, gingiva, cornea, liver, and kidney; the resulting clinical syndrome includes argyria, ocular injury, leukopenia, and toxicity in kidney, liver, and neurologic tissues ^[7]. Serum silver concentrations in modern burn patients treated with silver sulfadiazine can reach levels 558 times those of unexposed controls ^[32]. Whether these elevated systemic silver levels translate into clinically meaningful toxicity remains the core safety question.

Classification

Silver-based topical products in contemporary burn practice fall into four classes.

Silver sulfadiazine (SSD, Silvadene, Flamazine, Flammazine). A 1% cream applied directly to the wound, typically once or twice daily, with or without secondary gauze cover. SSD has been the standard conservative therapy for partial thickness burns for more than 40 years ^[3]. It is cheap, broadly available, and has an enviable safety record in burn treatment ^[10]. It does not penetrate eschar as efficiently as mafenide acetate ^[52], but it dominates the noneschar clinical space.

Silver nitrate solution (0.5%). A soaked gauze dressing application used intermittently through the day. In 1965, Moyer demonstrated that 0.5% was the minimum effective antibacterial concentration ^[1]. Silver nitrate dominated an early generation of burn care and is still used for specific indications including surfaces that tolerate wet dressings and patients in whom sulfa or cream-based agents are contraindicated. Serum and tissue silver levels from 10% silver nitrate used in burns produce no difference from 1% silver sulfadiazine cream ^[47], though silver nitrate solution brings its own electrolyte-derangement risk.

Nanocrystalline silver dressings (Acticoat, Acticoat 7, Acticoat Flex, Acticoat with Mepitel). A silver-coated polymer mesh that produces a moist healing environment along with the sustained release of ionic silver for improved microbial control ^[12]. The dressing releases silver over 3 to 7 days, dramatically reducing the frequency of dressing changes. Acticoat is the most studied nanocrystalline silver product in burn care ^[46].

Silver-impregnated hydrofiber and foam dressings (Aquacel Ag, Mepilex Ag, Askina Calgitrol Ag, Urgotul SSD, Mepitel Ag). Exudate-managing dressings into which silver is incorporated. Aquacel Hydrofiber is a moisture-retentive dressing with 1.2% w/w silver added to create Aquacel Ag ^[60]. Mepilex Ag is a soft silicone foam with silver salt ^[24]. These products fill the clinical niche of exudating partial thickness burns where dressing changes should be infrequent and atraumatic ^[23].

Assessment

Silver dressing selection starts with burn depth and the expected healing trajectory. Superficial partial thickness burns heal within 2-3 weeks with minimal scarring if no infection is present, and the skin blisters within hours [see [[burn-wound-dressing-selection]] for the decision framework]. Deep partial thickness and full thickness burns that are not headed for immediate excision require sustained antimicrobial coverage. Assessment is not a laboratory exercise. It is clinical: burn depth, wound size and location, likelihood of progression to surgical intervention, patient setting (inpatient vs outpatient), and the resources available to deliver the selected product.

Serial monitoring for systemic absorption is not routine in most modern practice. In a study of patients treated with Acticoat after burn surgery, the median total postoperative wound size was 12% TBSA, the median time to maximum serum silver was 9 days, the median maximum serum silver level was 56.8 μg/L, and the median serum level at 6 months was 0.8 μg/L, with no hematologic or biochemical indicators of toxicity ^[17]. Routine serum silver monitoring is not required for standard use. Symptom-driven monitoring for specific adverse events (methemoglobinemia with cerium-containing products, leukopenia when it was thought to be drug-attributable) has largely been replaced by careful clinical observation ^[11][10] [see Complications].

Management

Silver sulfadiazine

Silver sulfadiazine is applied as a 1% cream directly to the wound, either alone or under light gauze. Historical practice was twice-daily application, a regimen derived from early infection-control logic. A 150-patient before-after comparison of twice-daily versus once-daily SSD dressing changes found the wound infection rates were identical (5.33% in both groups), with average daily pain levels effectively the same (pre-change 5.27, post-change 5.25) ^[42]. Hospital-related complication rates were higher with twice-daily dressings (10.67% vs 6.67%), and once-daily dressing changes were associated with a decreased length of stay ^[42]. The average daily SSD consumption dropped from 320 g/day to 202 g/day with once-daily changes ^[42]. Once-daily SSD is a reasonable default absent a specific reason for more frequent changes.

The efficacy baseline for SSD is well established. In Pseudomonas-seeded rat burn models, silver sulfadiazine significantly eliminated P. aeruginosa more effectively in the tissue than Acticoat or chlorhexidine acetate, and SSD was the most effective agent in that specific treatment context ^[41]. The 2017 Cochrane antiseptics review, pooling three studies with 259 participants, found low-certainty evidence that there is no clear difference in the hazard of healing between silver-based antiseptics and SSD, though silver-based antiseptics may increase healing rate over time in some comparisons ^[4]. For over four decades SSD has anchored the treatment of partial thickness burns ^[3]. An earlier systematic review of 14 RCTs enrolling 877 participants also found that silver-containing dressings and topical silver were either no better or worse than control dressings in preventing wound infection and promoting healing, underscoring the heterogeneity of the evidence base ^[63].

Silver nitrate

Silver nitrate is typically delivered as 0.5% solution applied on continuous wet dressings ^[1]. In a controlled trial of superficial partial thickness burn wounds, the wound healing time in the silver nitrate group was 9.5 ± 2.7 days, significantly shorter than in the SSD group at 10.8 ± 3.4 days (P < 0.01), and silver nitrate ointment showed the same antibacterial effect as 1% SD-Ag cream while being less painful on open wounds ^[59]. On skin grafts after thermal injury, silver nitrate used as the topical antimicrobial agent produced no graft infections due to resistant organisms or yeast, in contrast to neomycin plus bacitracin ^[31]. Patients with 20 to 40% TBSA burns had less graft loss with silver nitrate than with Ringer's lactate alone ^[31]. Silver nitrate remains a specific tool rather than a first-line default in most modern U.S. burn centers.

Nanocrystalline silver (Acticoat)

Acticoat is the prototype nanocrystalline silver dressing. In the 1998 matched-pair RCT of 30 burn patients with symmetric wounds that established its modern role, patients found dressing removal less painful with Acticoat than with silver nitrate, and Acticoat was evaluated against silver nitrate on patient comfort, ease of use, and antimicrobial effectiveness ^[12]. The pain signal held up in subsequent trials. A prospective randomized trial of 47 paired observations found mean visual analog pain scores of 3.2 with Acticoat and 7.9 with silver sulfadiazine (P < 0.0001), and burn wound care with Acticoat was less painful than burn wound care with AgSD in selected partial thickness burns ^[13]. In 50 patients randomized to 1% silver sulfadiazine versus Acticoat, average pain scores were significantly lower in the Acticoat group (4 ± 0.6 versus 5 ± 0.7), and Acticoat provided a less painful alternative to wound care with 1% AgSD with comparable incidence of burn wound infection ^[14]. Dressing change frequency is reduced further with Acticoat: in postoperative meshed-autograft care, the median number of dressing changes was significantly less in the Acticoat group than in the 5% sulfamylon group, with equivalent wound healing and infectious complications ^[44].

Acticoat is used on donor sites as well as burn wounds, though its donor-site performance is less consistent. In a matched-pair RCT of 16 sites in 15 patients comparing Acticoat to Allevyn occlusive dressings, donor sites dressed with Allevyn were over 90% re-epithelialized at 9.1 ± 1.6 days while donor sites dressed with Acticoat required 14.5 ± 6.7 days to reach the same endpoint (P = 0.004) ^[43]. The Perth Burn Unit audit captured the system-level effect on burn-wound patients. When Silvazine (silver sulfadiazine plus chlorhexidine digluconate cream) was replaced with Acticoat for in-patient treatment of early burn wounds, the incidence of infection and antibiotic use fell from 55% (28/51) and 57% (29/51) in 2000 to 10.5% (2/19) and 5.2% (1/19) in 2002 ^[15]. Average length of hospital stay dropped from 17.25 days with Silvazine to 12.5 days with Acticoat, a difference of 4.75 days, with a total cost savings of US$30,450 across eight matched patient pairs ^[15]. In pediatric care, children treated with Acticoat as outpatients spent an average of 0.83 days admitted versus 13.85 days for children treated with silver sulfadiazine (P < 0.001) ^[16]. The 2017 systematic review and meta-analysis of nanocrystalline silver versus alternative silver delivery systems pooled eight studies comparing nanocrystalline silver and SSD and one study comparing nanocrystalline silver and silver nitrate, and found a statistically significant reduction in infections (OR 0.21, 95% CI 0.07-0.62, P = 0.005), length of stay in hospital (mean difference -4.74 days, 95% CI -5.79 to -3.69, P < 0.00001), and surgical procedures (OR 0.40, 95% CI 0.28-0.56, P < 0.00001) with nanocrystalline silver ^[5]. An earlier 2009 systematic review of five randomized trials in 285 burn patients found nanocrystalline silver associated with a significantly lower incidence of infection than silver sulfadiazine (9.5% vs 27.8%, OR 0.14, 95% CI 0.06-0.35, P < 0.001), lower costs, and decreased pain during dressing changes ^[65]. Pooled against Vaseline gauze as comparator, the 2017 Cochrane review found burns treated with nanocrystalline silver dressings probably have a slightly shorter mean time to healing (difference in means -3.49 days, 95% CI -4.46 to -2.52; moderate-certainty evidence) ^[4]. The nanocrystalline silver meta-analytic signal points in one direction.

Silver-impregnated hydrofiber (Aquacel Ag)

Aquacel Ag is a hydrofiber dressing containing ionic silver that reduces burn wound infection and promotes antimicrobial activity ^[51]. The 2006 RCT that launched it into wide adult use found AQUACEL Ag dressing was associated with less pain and anxiety during dressing changes, less burning and stinging during wear, fewer dressing changes, less nursing time, and fewer procedural medications compared with silver sulfadiazine ^[19]. The AQUACEL Ag dressing protocol tended to have lower total treatment costs ($1,040 vs $1,180) and a greater rate of re-epithelialization (73.8% vs 60.0%), resulting in cost-effectiveness per burn healed of $1,409.06 for AQUACEL Ag dressing versus $1,967.95 for silver sulfadiazine ^[19]. A subsequent prospective randomized outpatient trial confirmed the healing-time benefit: time-to-wound closure was 10 ± 3 days in the Aquacel Ag group versus 13.7 ± 4 days in the silver sulfadiazine group (P < 0.02), pain scores at days 1, 3, and 7 were significantly lower with Aquacel Ag (4.1 vs 6.1 at day 1), and total cost was $52 ± 29 versus $93 ± 36 per patient ^[20]. Aquacel Ag increased time to healing, decreased pain, and increased patient convenience at lower total cost ^[20].

On facial partial thickness burns, Aquacel Ag reduced mean time to re-epithelialization from 12.4 days (MEBO group) to 10.5 days (Aquacel Ag group, P < 0.05), with fewer dressing changes and improved scar quality ^[22]. The 100-patient prospective RCT comparing Aquacel Ag directly against Acticoat found similar healing times and bacterial control, but a statistically significant difference in favor of Aquacel Ag for average ease of use (P < 0.001), average ease of application (P = 0.001), patient pain (P < 0.001), patient comfort (P = 0.017), silver staining (P < 0.001), and cost-effectiveness (P < 0.001) ^[21]. Aquacel Ag significantly increased comfort for patients and nurses and was significantly more cost-effective than Acticoat for that indication ^[21]. The 2023 meta-analysis of 794 burn patients across 11 trials showed that Aquacel Ag reduces inflammatory reactions (lower TNF-α levels) compared with silver sulfadiazine ^[51].

At the system level, the introduction of hydrofiber dressings reduced the skin grafting rate in mixed partial thickness scald burns up to 10% TBSA in children aged 0-4: after introduction, the surgery rate fell from 20.7% with silver sulfadiazine to 11.6% with hydrofiber dressings (P < 0.01), and hospital length of stay was reduced ^[28].

Silver-containing soft silicone foam (Mepilex Ag)

Mepilex Ag is a silver-impregnated foam with a soft silicone contact layer. The 101-subject RCT of Mepilex Ag versus silver sulfadiazine cream found a mean total cost of treatment of $309 vs $513 (P < 0.001), an incremental cost-effectiveness ratio of $1,688 in favor of the soft silicone foam dressing, and mean healing rates of 71.7% versus 60.8% ^[24]. Subjects reported significantly less pain at application (P = 0.02) and during wear (P = 0.048) of the Mepilex Ag dressing, and clinicians reported the dressing was significantly easier to use (P = 0.03) and more flexible (P = 0.04) ^[24]. Both treatments were well tolerated, though the total incidence of adverse events was higher in the control group ^[24]. In the multicenter 71 vs 82 patient RCT of Mepilex Ag versus SSD in deep partial thickness burns, there was no significant difference between groups in time to healing (79% healed in both groups after median 15-16 days), but the mean total number of dressings was 3.06 in the Mepilex Ag group versus 14.0 in the SSD group (P < 0.0001) ^[23]. Mepilex Ag allowed undisturbed healing with dramatically fewer dressing changes ^[23].

The pediatric cost-effectiveness analysis comparing three silver dressings in children 0-15 years with partial thickness burns under 10% TBSA found costs of $94.45 (Mepilex Ag) versus $196.66 (Acticoat with Mepitel) versus $244.90 (Acticoat), with 99% and 97% probability that Mepilex Ag dominated (cheaper and more effective) Acticoat and Acticoat with Mepitel, respectively ^[25]. Mepilex Ag was the dominant dressing choice in that trial ^[25]. The adult 4-arm RCT comparing Biobrane, Acticoat, Mepilex Ag, and Aquacel Ag in 119 patients reached a similar conclusion: Mepilex Ag had reduced time to re-epithelialization compared with Biobrane (IRR 1.26; 95% CI 1.07-1.48, P < 0.01), and economic analysis showed a 99%, 71%, and 53% probability that Mepilex Ag dominated Biobrane, Acticoat, and Aquacel Ag, respectively ^[26]. Mepilex Ag achieved faster re-epithelialization and better cost-effectiveness in that trial ^[26].

Head-to-head among silver dressings

The three silver dressings are not interchangeable. The Brown 2016 pediatric emergency department RCT comparing Acticoat and Aquacel Ag found no difference in day-10 epithelialization (Acticoat 93 ± 14%, Aquacel Ag 94 ± 17%, P = 0.89), with adverse events rare in both groups, but Aquacel Ag required significantly fewer dressing changes per patient (median 1 vs 2, P = 0.03) ^[27]. Both dressings were effective, and Aquacel Ag was superior on dressing-change burden ^[27]. The patient and dressing-change mismatch reappears consistently: Aquacel Ag tends to win on comfort and ease-of-use, Mepilex Ag tends to win on cost-effectiveness, and nanocrystalline silver tends to win on sustained antimicrobial delivery and wound bed isolation.

Duration and switching

The appropriate duration of silver therapy is the duration until the wound heals or reaches excision. Meta-analytic data show that overall silver-based antiseptic regimens do not differ substantially from silver sulfadiazine in pooled hazard of healing ^[4]. The conservative position that SSD is the only defensible default for partial thickness burns is no longer supported: a systematic review concluded that the standard use of SSD in the conservative treatment of burn wounds can no longer be supported because new dressings achieve faster wound healing ^[3]. The earlier Cochrane review of dressings for superficial and partial thickness burns reached a parallel conclusion across 30 RCTs, finding silver sulfadiazine consistently associated with poorer healing outcomes than biosynthetic, silver-containing, and silicon-coated dressings ^[61]. The rate of infection is significantly higher in SSD-treated groups compared with dressings without silver ^[6]. Non-silver treatment in pediatric partial thickness burns led to shorter wound healing time (weighted mean difference -3.43 days, 95% CI -4.78 to -2.07), fewer dressing changes, and shorter length of stay compared with silver sulfadiazine ^[35]. The Cochrane prophylaxis review found silver sulfadiazine associated with a statistically significant increase in burn wound infection compared with dressings or skin substitutes (OR 1.87; 95% CI 1.09 to 3.19) and with significantly longer length of hospital stay (MD 2.11 days; 95% CI 1.93 to 2.28) ^[36]. The switching decision is typically made at days 3-7, when the wound depth is clearer and the trajectory is established.

Complications

Argyria and cutaneous pigmentation

Silver deposition has been found in the skin, gingiva, cornea, liver, and kidney of patients treated with silver sulfadiazine, causing argyria, ocular injury, leukopenia, and toxicity in kidney, liver, and neurologic tissues ^[7]. Tissue silver concentrations in one burn patient who died of renal failure after eight days of treatment were 970 μg/g wet tissue in cornea, 14 μg/g in liver, and 0.2 μg/g in kidney ^[7]. Argyria in current practice is rare. A 2025 systematic scoping review of silver dressings in infants identified 110 sources reporting complications, and no cases of argyria, kernicterus, or methemoglobinemia were reported ^[34]. Transient wound staining and silver pigmentation are common with silver sulfadiazine ^[10].

Methemoglobinemia

Methemoglobinemia is classically associated with cerium nitrate-silver sulfadiazine combinations rather than SSD alone, and it is rare but oft cited ^[11]. In a single-center review of 157 patients treated with cerium nitrate-silver sulfadiazine cream, methemoglobinemia occurred in 9.6% (15 patients), with 73.3% of those having maximum methemoglobin levels at 72 hours or later from the first application ^[11]. Only one patient developed clinically significant methemoglobinemia ^[11]. Patients with TBSA 20% or greater were more likely to develop methemoglobinemia (OR 9.32; 95% CI 2.08-65.73, P = 0.0078); neither dose nor duration was a significant predictor ^[11]. Cerium nitrate-silver sulfadiazine can be used in asymptomatic patients with TBSA under 20% without serial blood gas monitoring, but vigilant symptom-based monitoring is appropriate at TBSA 20% or greater ^[11]. Methemoglobinemia from pure silver sulfadiazine without cerium is exceptional. Reported side effects of silver sulfadiazine include allergic reactions to its sulfadiazine moiety, silver staining of the treated burn wound, hyperosmolality, methemoglobinemia, and hemolysis in patients with congenital G6PD deficiency ^[10].

Leukopenia

Early post-burn leukopenia was for years attributed to silver sulfadiazine therapy. The initial case series reported that leukopenia incidence increased dramatically in one burn unit in 1978 and was observed only in silver sulfadiazine-treated patients, not in patients treated with other agents ^[8]. Subsequent work undermined that association. In a comparative study of 40 patients treated with silver sulfadiazine and 30 treated with silver nitrate, leukopenia (WBC count ≤5000/mm³) occurred in 47.5% and 43.3% respectively, with no statistical difference between groups, suggesting that silver sulfadiazine was not the cause of the leukopenia observed early after burn injury ^[9]. Early post-burn leukopenia, once thought to be a side effect of silver sulfadiazine, is no longer regarded as such since it has been found to occur with the use of other burn topical agents, and its presence is no longer an indication to discontinue silver sulfadiazine burn wound therapy ^[10].

Cytotoxicity

In vitro cytotoxicity of silver against keratinocytes and fibroblasts is well documented. The cytotoxic effects of Acticoat and Flamazine cream were dependent on exposure time and cell type in primary and immortal skin cells; after 24-hour exposure, both Acticoat and Flamazine cream were toxic to all tested cell lines ^[33]. In contrast, a novel silver hydrogel and PolyMem Silver showed low cytotoxicity to all tested cell lines at every time interval ^[33]. When chlorhexidine is added to nanocrystalline silver, antimicrobial activity improves against S. aureus and P. aeruginosa, but cytotoxicity is exacerbated when dressings are coated with chlorhexidine and antimicrobial peptide formulations ^[55]. In burn patients treated with silver sulfadiazine, silver ion serum levels can reach 558 times those of unexposed controls, and in vitro exposure of inflammatory cells to silver ion at comparable levels shows decreased reactive oxygen species production by mononuclear and polymorphonuclear cells and substantially decreased production of IL-1β, IL-6, IL-8, IL-10, and TNF-α ^[32]. These findings suggest that silver ion may contribute to negative outcomes after burns by decreasing the primary defense mechanism and altering cytokine production ^[32]. Clinically, the cytotoxicity signal competes with the antimicrobial benefit; translation from in vitro to patient outcomes remains incomplete.

Systemic absorption and organ toxicity

Silver from topical application is absorbed through burned skin. In burn patients treated with silver sulfadiazine cream, plasma silver concentrations can reach 310 μg/L and urine silver up to 400 μg/day ^[7]. Silver serum levels in patients treated with Acticoat reached a median maximum of 56.8 μg/L at a median of 9 days, with no hematologic or biochemical indicators of toxicity ^[17]. A rat study comparing silver absorption from silver sulfadiazine foam versus nanocrystalline silver found detectable silver in spleen, kidney, liver, brain, testis, lung, heart, and muscle tissue, with higher parenchymal organ levels in the nanocrystalline silver group than the silver sulfadiazine foam group ^[45]. In a rat deep second-degree burn model, serum silver levels were significantly elevated with both AgiCoat and Acticoat compared with baseline, and AgiCoat showed significant hepatotoxicity compared with Acticoat (P = 0.002), though no pathological changes were observed in brain, kidneys, spleen, heart, or lungs ^[49]. Nanosilver dressings can cause liver toxicity but not kidney, brain, spleen, heart, or lung toxicity in animal models ^[49]. The clinical implication is that extended use on large wounds, in infants, or in patients with compromised hepatic function warrants thoughtful risk-benefit assessment. The general toxicologic principle is that silver presents a relatively low toxic threat to humans under unintentional exposure, but subtle toxic effects may be predictable and expected as intentional pharmaceutical utilization increases ^[48].

Silver resistance

Strains of Pseudomonas aeruginosa resistant to silver sulfadiazine have appeared ^[30]. In a four-year molecular-epidemiology study of a burn wound center, 16% of 441 patients were colonized with P. aeruginosa, and 12 of 48 distinct AFLP genotypes colonized 57 patients; two predominant genotypes drove recurrent outbreaks, one endemic multidrug-resistant strain and one silver sulfadiazine-resistant strain ^[29]. The SSD-resistant strain showed higher prevalence in burn wound samples than in sputum, suggesting anatomic habitat selection was associated with adaptive resistance ^[29]. Silver resistance emergence remains a real but geographically variable phenomenon. In the Acticoat literature, no evidence of resistance or cytotoxicity to nanocrystalline silver emerged in the initial series ^[18], though the sustained-release format may reduce rather than eliminate resistance selection pressure.

Special Considerations

Pediatric

Silver-based dressings are extensively used in pediatric burn care but the evidence base has historically leaned on adult trials. The evidence for application of silver-containing dressings and topicals in the treatment of partial thickness burns in pediatric patients is largely based on clinical trials involving adult patients despite the important differences between the skin of children and adults ^[35]. A parallel 2014 systematic review of pediatric partial thickness burn treatment reviewed 34 comparative studies, with silver sulfadiazine or silver sulfadiazine/chlorhexidine as the standard of care in 16 of them; membranous dressings like Biobrane and amnion membrane outperformed standard of care on epithelialization rate, length of hospital stay, and pain ^[64]. In a meta-analysis of seven RCTs with 473 pediatric participants using SSD as control, non-silver treatment led to shorter wound healing time (weighted mean difference -3.43 days, 95% CI -4.78 to -2.07), fewer dressing changes, and shorter length of hospital stay compared with SSD ^[35]. The conclusion was that non-silver treatment may be preferred over silver sulfadiazine in children, but the underlying trials were mostly of moderate quality with high risk of bias ^[35]. Within the silver-dressing space in children, Mepilex Ag dominated Acticoat and Acticoat with Mepitel on cost-effectiveness ^[25], and Aquacel Ag required fewer dressing changes than Acticoat ^[27]. In young children 0-4 years with partial thickness scald burns up to 10% TBSA, introduction of hydrofiber dressings reduced surgical interventions from 20.7% to 11.6% (P < 0.01) and limited hospital length of stay compared with silver sulfadiazine ^[28].

Infants and neonates

Reports of elevated serum silver and concern over systemic toxicity have meant that silver dressings in young children have been questioned ^[34]. A 2025 systematic scoping review of silver dressings in infants identified 599 sources with 110 included for review. Complications were described in 31 sources, with the most frequent being wound infection; no cases of argyria, kernicterus, or methemoglobinemia were reported; six sources documented elevated serum silver levels in infants, but none reported adverse events related to this ^[34]. The pragmatic recommendation from that review was to reserve silver dressings in infants under 1 year for wounds at high risk of infection, and to consider wound area and duration of treatment when assessing the risk of systemic silver absorption ^[34]. Silver dressings are not absolutely contraindicated in infants, but the threshold for use should be higher.

Sulfa allergy and G6PD deficiency

Silver sulfadiazine is the metallic salt of a sulfonamide derivative ^[10]. Patients with a documented sulfonamide allergy should not receive silver sulfadiazine. Patients with congenital G6PD deficiency are at risk of hemolysis from the sulfadiazine moiety, and the risk is independent of the silver ^[10]. Nanocrystalline silver, Aquacel Ag, Mepilex Ag, and silver nitrate do not contain sulfadiazine and are the appropriate alternatives. Cross-resistance between sulfonamide and chlorhexidine diphosphanilate or its components has not been observed in comparator studies of topical chlorhexidine in burn wound sepsis ^[56].

Face, eyelids, and mucosal surfaces

Facial burns tolerate silver sulfadiazine and Aquacel Ag well. On partial thickness facial burns, Aquacel Ag produces shorter re-epithelialization, fewer dressing changes, and improved scar quality compared with MEBO open dressing ^[22]. Application to the eyelids or over the ocular surface is limited by the potential for ocular silver deposition; silver has been found in the cornea of SSD-treated patients ^[7]. Avoid application to the eyelid margin and conjunctival surface.

MRI compatibility

Burn inpatients routinely undergo MRI for trauma workup or evaluation of occult injury. In vitro testing of silver-based dressings across field strengths has shown no deflection, no torsion, and average heating between 0 and 0.2 °C, supporting imaging without dressing removal when clinical workflow favors it ^[67].

Large TBSA

Patients with burns covering more than 50% of body surface area outstrip the bacteriostatic capacity of silver sulfadiazine alone, which does not offer sufficient protection to prevent or retard gram-negative bacterial growth ^[1]. Monafo introduced the combined preparation silver sulphadiazine and cerium nitrate for this indication ^[1]. In patients with moderate-to-severe burns randomized to topical silver sulfadiazine versus SSD-cerium nitrate, four deaths occurred in the SSD group versus one in the SSD-CN group, and more patients with higher risk severity survived in the SSD-CN group ^[39]. The SSD-CN group had faster re-epithelialization of partial thickness burns (by 8 days), faster escharolysis allowing planned excisions 11 days earlier, and significantly shorter hospital stay (23.3 vs 30.7 days; P = 0.03) ^[39]. This signal is consistent with the pooled 2017 Cochrane meta-analysis, which found there may be fewer deaths in groups treated with cerium nitrate plus SSD compared with SSD alone (RR 0.22, 95% CI 0.05 to 0.99; 2 studies, 214 participants; low-certainty evidence) ^[4]. Patients with large TBSA who are candidates for early excision should not be anchored on topical silver as definitive management; silver buys time until surgery.

Outcomes

The outcomes most robustly demonstrated across silver dressing comparisons are shorter wound healing time with newer dressings than with silver sulfadiazine ^[6], and reduced length of hospital stay, dressing changes, and surgical procedures with nanocrystalline silver compared with silver sulfadiazine and silver nitrate ^[5]. A single-center pediatric cost analysis demonstrated that nanocrystalline silver clearly saved costs compared with three other regimens, with cost savings resulting primarily from the decreased number of dressings and shorter hospital stay ^[50]. The Perth audit showed 4.75 fewer hospital days and US$30,450 in savings across eight matched pairs with Acticoat versus Silvazine ^[15]. In pediatric outpatient care, Acticoat cut inpatient stay from 13.85 days to 0.83 days (P < 0.001) without increasing complications or skin grafting ^[16]. The 2023 meta-analysis of Aquacel Ag showed reduced inflammatory markers versus silver sulfadiazine ^[51]. On mortality, silver-based dressings have not been shown to reduce mortality in any adequately powered controlled trial; the intermediate outcomes of healing, infection, hospital days, and dressing-change burden are the ones that justify the switch.

Scar outcome is not reliably differentiated among silver dressings. In a 12-month follow-up RCT of children with partial thickness scalds treated with porcine xenograft versus silver foam dressing, there were no differences in POSAS, VSS total scores, or incidence of hypertrophic scarring between dressings, and hypertrophic scarring was associated with healing times beyond 14 days rather than with dressing choice ^[53]. Hypopigmentation of the burn site was present in 25.8% of children who re-epithelialized within 2 weeks in a post-hoc analysis of pediatric partial thickness burns ^[54]. Days to re-epithelialization is a significant predictor of skin and scar quality at 3 and 6 months regardless of dressing choice ^[54].

Controversies and Evidence Gaps

Is silver sulfadiazine still a defensible default?

The 2016 systematic review of silver sulphadiazine in the conservative treatment of partial thickness burns concluded that many dressings show superior healing properties compared with SSD, that no dressing shows a clear benefit over SSD regarding infection, and that the standard use of SSD in the conservative treatment of burn wounds can no longer be supported because rapid wound closure is essential to optimal functional and aesthetic outcome ^[3]. The 2019 meta-analysis of 24 studies confirmed a statistically favorable difference in time to healing for silver dressings (MD 3.83 days; 95% CI 2.03-5.62) and for non-silver dressings (MD 2.9 days; 95% CI 0.81-5.00) compared with SSD, with no difference in infection rate between SSD and silver dressings but significantly higher infection rates with SSD compared with non-silver dressings ^[6]. The 2014 pediatric meta-analysis reached the same conclusion in children: nonsilver treatment led to shorter healing time, fewer dressing changes, and shorter length of stay ^[35]. The 2020 meta-analysis of nanosilver versus silver sulfadiazine confirmed shorter wound healing time with nanosilver (P < 0.001) and significantly reduced pain (P < 0.001), though the wound healing rate on day 15 did not differ significantly ^[37]. The 2017 Dissemond silver meta-analysis of 39 studies showed that 28 of 39 studies with statistically significant outcome parameters favored silver, and that the evidence base for silver in wound management is significantly better than perceived in the current scientific debate ^[38]. A 2019 meta-analysis of 11 RCTs found alternative treatments to silver sulfadiazine were superior in mean time for complete wound healing (mean difference -4.26 days, 95% CI -5.96 to -2.56, P < 0.00001) ^[66]. The practical reality is that SSD is cheap, familiar, and usable in resource-constrained settings, and continues to be used in many burn programs worldwide despite the mounting signal that newer dressings outperform it on healing speed, pain, and dressing burden.

Nanocrystalline silver versus silver-impregnated foam and hydrofiber

The three modern silver dressings have not been definitively ranked against each other. Head-to-head trials show Aquacel Ag and Acticoat produce comparable healing and bacterial control ^[21][27], Mepilex Ag dominates on cost-effectiveness in pediatric and adult 4-arm trials ^[25][26], and Aquacel Ag wins on comfort and reduced dressing changes versus Acticoat ^[21]. A separate 2017 systematic review with indirect treatment comparison of nanocrystalline silver, silver-impregnated hydrofiber, and silver-impregnated foam dressings found nanocrystalline silver associated with shorter length of stay than hydrofiber (P = 0.027) and shorter time to healing than foam (P = 0.0328), with no statistically significant differences in infection rates or surgical procedures between the three approaches ^[62]. Individual practitioner and unit preference is rationally informed but not driven by a single winning trial.

Eschar penetration

Silver sulfadiazine penetrates eschar less efficiently than mafenide acetate. In infected burn rat models, mafenide acetate and silver sulfadiazine plus chlorhexidine digluconate 0.2% produced lower mean organism concentrations in full-thickness eschar and subjacent muscle than silver sulfadiazine alone ^[52]. In the Ulkür comparison, eschar concentrations did not differ significantly between Acticoat and chlorhexidine acetate groups, but silver sulfadiazine significantly eliminated P. aeruginosa more effectively in the treatment tissue ^[41]. In practice, deep full-thickness injuries with established eschar are managed with mafenide acetate or silver nitrate rather than SSD where eschar penetration matters most [see [[non-silver-topical-antimicrobials]]].

Silver resistance emergence

Silver resistance has been documented as an endemic strain phenomenon in at least one burn wound center ^[29]. Whether sustained-release nanocrystalline silver reduces or accelerates resistance selection is not definitively answered. The original Acticoat series reported no evidence of resistance or cytotoxicity ^[18], but serial surveillance in high-usage centers is warranted.

Cytotoxicity versus antimicrobial benefit

The in vitro cytotoxicity of silver against human keratinocytes and fibroblasts is demonstrated across multiple cell lines and exposure times ^[33]. In serial monitoring of burn patients treated with silver sulfadiazine, serum silver ion reached 558 times the unexposed control level, with downstream effects on leukocyte respiratory burst and cytokine production ^[32]. Whether these cell-level effects translate into clinically meaningful impairment of wound healing or host defense has not been resolved. The clinical trial record shows improved wound healing with most modern silver dressings, which constrains the cytotoxicity interpretation to a sub-clinical concern at standard doses.

Cost-effectiveness comparators

Cost-effectiveness comparisons among silver products are affected by healthcare system, patient setting, and the counterfactual. In a 100-patient RCT, nanocrystalline silver dressings produced significantly fewer dressing changes (mean 4.1 vs 9.6, P < 0.001) and cost reductions in materials, human resources, and administrative labor relative to SSD, yet mean total cost with nanocrystalline silver was higher than with 1% SSD ($496.37 vs $274.73, P = 0.001) ^[57]. A cost-utility analysis comparing skin allograft versus topical silver dressings for partial thickness burns found skin allograft was cost-effective versus Mepilex Ag in 62.1% of simulations and versus SSD in 64.9% of simulations at a willingness-to-pay threshold of $100,000/QALY ^[58]. The silver-dressing space contains real cost-effectiveness signal, but it is modulated by clinical setting, wound trajectory, and the chosen alternative.

References

[1] Klasen HJ. "A historical review of the use of silver in the treatment of burns. II. Renewed interest for silver." Burns 2000. PMID: 10716355

[2] Fox CL, Modak SM. "Mechanism of silver sulfadiazine action on burn wound infections." Antimicrob Agents Chemother 1974. PMID: 15825409

[3] Heyneman A, Hoeksema H, Vandekerckhove D, et al. "The role of silver sulphadiazine in the conservative treatment of partial thickness burn wounds: A systematic review." Burns 2016. PMID: 27126813

[4] Norman G, Christie J, Liu Z, et al. "Antiseptics for burns." Cochrane Database Syst Rev 2017. PMID: 28700086

[5] Nherera LM, Trueman P, Roberts CD, et al. "A systematic review and meta-analysis of clinical outcomes associated with nanocrystalline silver use compared to alternative silver delivery systems in the management of superficial and deep partial thickness burns." Burns 2017. PMID: 28161149

[6] Nímia HH, Carvalho VF, Isaac C, et al. "Comparative study of Silver Sulfadiazine with other materials for healing and infection prevention in burns: A systematic review and meta-analysis." Burns 2019. PMID: 29903603

[7] Wan AT, Conyers RA, Coombs CJ, et al. "Determination of silver in blood, urine, and tissues of volunteers and burn patients." Clin Chem 1991. PMID: 1914165

[8] Caffee HH, Bingham HG. "Leukopenia and silver sulfadiazine." J Trauma 1982. PMID: 7097818

[9] Thomson PD, Moore NP, Rice TL, et al. "Leukopenia in acute thermal injury: evidence against topical silver sulfadiazine as the causative agent." J Burn Care Rehabil 1989. PMID: 2793919

[10] Fuller FW. "The side effects of silver sulfadiazine." J Burn Care Res 2009. PMID: 19349889

[11] Reese AD, Keyloun JW, Garg G, et al. "Compounded Cerium Nitrate-Silver Sulfadiazine Cream is Safe and Effective for the Treatment of Burn Wounds: A Burn Center's 4-Year Experience." J Burn Care Res 2022. PMID: 34543402

[12] Tredget EE, Shankowsky HA, Groeneveld A, et al. "A matched-pair, randomized study evaluating the efficacy and safety of Acticoat silver-coated dressing for the treatment of burn wounds." J Burn Care Rehabil 1998. PMID: 9848045

[13] Varas RP, O'Keeffe T, Namias N, et al. "A prospective, randomized trial of Acticoat versus silver sulfadiazine in the treatment of partial-thickness burns: which method is less painful?" J Burn Care Rehabil 2005. PMID: 16006842

[14] Muangman P, Chuntrasakul C, Silthram S, et al. "Comparison of efficacy of 1% silver sulfadiazine and Acticoat for treatment of partial-thickness burn wounds." J Med Assoc Thai 2006. PMID: 16881426

[15] Fong J, Wood F, Fowler B. "A silver coated dressing reduces the incidence of early burn wound cellulitis and associated costs of inpatient treatment: comparative patient care audits." Burns 2005. PMID: 15993301

[16] Peters DA, Verchere C. "Healing at home: Comparing cohorts of children with medium-sized burns treated as outpatients with in-hospital applied Acticoat to those children treated as inpatients with silver sulfadiazine." J Burn Care Res 2006. PMID: 16566565

[17] Vlachou E, Chipp E, Shale E, et al. "The safety of nanocrystalline silver dressings on burns: a study of systemic silver absorption." Burns 2007. PMID: 17959313

[18] Dunn K, Edwards-Jones V. "The role of Acticoat with nanocrystalline silver in the management of burns." Burns 2004. PMID: 15327800

[19] Caruso DM, Foster KN, Blome-Eberwein SA, et al. "Randomized clinical study of Hydrofiber dressing with silver or silver sulfadiazine in the management of partial-thickness burns." J Burn Care Res 2006. PMID: 16679897

[20] Muangman P, Pundee C, Opasanon S, et al. "A prospective, randomized trial of silver containing hydrofiber dressing versus 1% silver sulfadiazine for the treatment of partial thickness burns." Int Wound J 2010. PMID: 20528992

[21] Verbelen J, Hoeksema H, Heyneman A, et al. "Aquacel Ag dressing versus Acticoat dressing in partial thickness burns: a prospective, randomized, controlled study in 100 patients. Part 1: burn wound healing." Burns 2014. PMID: 24045072

[22] Mabrouk A, Boughdadi NS, Helal HA, et al. "Moist occlusive dressing (Aquacel Ag) versus moist open dressing (MEBO) in the management of partial-thickness facial burns: a comparative study in Ain Shams University." Burns 2012. PMID: 22100189

[23] Tang H, Lv G, Fu J, et al. "An open, parallel, randomized, comparative, multicenter investigation evaluating the efficacy and tolerability of Mepilex Ag versus silver sulfadiazine in the treatment of deep partial-thickness burn injuries." J Trauma Acute Care Surg 2015. PMID: 25909422

[24] Silverstein P, Heimbach D, Meites H, et al. "An open, parallel, randomized, comparative, multicenter study to evaluate the cost-effectiveness, performance, tolerance, and safety of a silver-containing soft silicone foam dressing vs silver sulfadiazine cream." J Burn Care Res 2011. PMID: 21979855

[25] Gee Kee E, Stockton K, Kimble RM, et al. "Cost-effectiveness of silver dressings for paediatric partial thickness burns: An economic evaluation from a randomized controlled trial." Burns 2017. PMID: 28408145

[26] Aggarwala S, Harish V, Roberts S, et al. "Treatment of Partial Thickness Burns: A Prospective, Randomized Controlled Trial Comparing Four Routinely Used Burns Dressings in an Ambulatory Care Setting." J Burn Care Res 2021. PMID: 32930784

[27] Brown M, Dalziel SR, Herd E, et al. "A Randomized Controlled Study of Silver-Based Burns Dressing in a Pediatric Emergency Department." J Burn Care Res 2016. PMID: 26171678

[28] Dokter J, Boxma H, Oen IM, et al. "Reduction in skin grafting after the introduction of hydrofiber dressings in partial thickness burns: a comparison between a hydrofiber and silver sulphadiazine." Burns 2013. PMID: 22480921

[29] Pirnay JP, De Vos D, Cochez C, et al. "Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone." J Clin Microbiol 2003. PMID: 12624051

[30] Modak S, Stanford J, Friedlaender J. "Control of burn wound infections by pefloxacin and its silver derivative." Burns Incl Therm Inj 1984. PMID: 6586256

[31] Livingston DH, Cryer HG, Miller FB, et al. "A randomized prospective study of topical antimicrobial agents on skin grafts after thermal injury." Plast Reconstr Surg 1990. PMID: 2243846

[32] Mimura ECM, Favoreto JPM, Favero ME, et al. "Silver serum levels in burned patients treated with silver sulfadiazine and its toxicity on inflammatory cells." Burns 2020. PMID: 31839506

[33] Boonkaew B, Kempf M, Kimble R, et al. "Cytotoxicity testing of silver-containing burn treatments using primary and immortal skin cells." Burns 2014. PMID: 24767717

[34] O'Donohoe PK, Leon R, Orr DJA, et al. "Safety of Silver Dressings in Infants; a Systematic Scoping Review." J Burn Care Res 2025. PMID: 39165069

[35] Rashaan ZM, Krijnen P, Klamer RR, et al. "Nonsilver treatment vs. silver sulfadiazine in treatment of partial-thickness burn wounds in children: a systematic review and meta-analysis." Wound Repair Regen 2014. PMID: 24899251

[36] Barajas-Nava LA, López-Alcalde J, Roqué i Figuls M, et al. "Antibiotic prophylaxis for preventing burn wound infection." Cochrane Database Syst Rev 2013. PMID: 23740764

[37] Li Y, Wang L, He X. "Meta-Analysis of the Therapeutic Effect of Nanosilver on Burned Skin." J Nanosci Nanotechnol 2020. PMID: 32711650

[38] Dissemond J, Böttrich JG, Braunwarth H, et al. "Evidence for silver in wound care - meta-analysis of clinical studies from 2000-2015." J Dtsch Dermatol Ges 2017. PMID: 28485879

[39] de Gracia CG. "An open study comparing topical silver sulfadiazine and topical silver sulfadiazine-cerium nitrate in the treatment of moderate and severe burns." Burns 2001. PMID: 11164668

[40] Wright JB, Lam K, Hansen D. "Efficacy of topical silver against fungal burn wound pathogens." Am J Infect Control 1999. PMID: 10433674

[41] Ulkür E, Oncül O, Karagöz H, et al. "Comparison of silver-coated dressing (Acticoat), chlorhexidine acetate 0.5% (Bactigrass), and silver sulfadiazine 1% (Silverdin) for topical antibacterial effect in Pseudomonas aeruginosa-contaminated, full-skin thickness burn wounds in rats." J Burn Care Rehabil 2005. PMID: 16151289

[42] Lagziel T, Asif M, Born L, et al. "Evaluating the Efficacy, Safety, and Tolerance of Silver Sulfadiazine Dressings Once Daily Versus Twice Daily in the Treatment of Burn Wounds." J Burn Care Res 2021. PMID: 34363678

[43] Innes ME, Umraw N, Fish JS, et al. "The use of silver coated dressings on donor site wounds: a prospective, controlled matched pair study." Burns 2001. PMID: 11525858

[44] Silver GM, Robertson SW, Halerz MM, et al. "A silver-coated antimicrobial barrier dressing used postoperatively on meshed autografts: a dressing comparison study." J Burn Care Res 2007. PMID: 17667837

[45] Pfurtscheller K, Petnehazy T, Goessler W, et al. "Transdermal uptake and organ distribution of silver from two different wound dressings in rats after a burn trauma." Wound Repair Regen 2014. PMID: 25139317

[46] Khundkar R, Malic C, Burge T. "Use of Acticoat dressings in burns: what is the evidence?" Burns 2010. PMID: 20346592

[47] Kartal A, Tatkan Y, Belviranli M. "Serum and tissue silver levels after burns treated with silver compounds." J Chir (Paris) 1989. PMID: 2621235

[48] Hollinger MA. "Toxicological aspects of topical silver pharmaceuticals." Crit Rev Toxicol 1996. PMID: 8726163

[49] Karimi H, Latifi NA, Mehrjerdi AZ, et al. "Histopathological Changes of Organs (Lungs, Liver, Kidney, and Brain) After Using Two Types of AgiCoat and Acticoat Nanosilver Dressings on Deep Second-Degree Burn in Rat." J Burn Care Res 2020. PMID: 31400763

[50] Cox SG, Cullingworth L, Rode H. "Treatment of paediatric burns with a nanocrystalline silver dressing compared with standard wound care in a burns unit: a cost analysis." S Afr Med J 2011. PMID: 22272852

[51] Wu JJ, Zhang F, Liu J, et al. "Effect of silver-containing hydrofiber dressing on burn wound healing: A meta-analysis and systematic review." J Cosmet Dermatol 2023. PMID: 36683314

[52] Gray JH, Henry DA, Forbes M. "Comparison of silver sulphadiazine 1 per cent, silver sulphadiazine 1 per cent plus chlorhexidine digluconate 0.2 per cent and mafenide acetate 8.5 per cent for topical antibacterial effect in infected full skin thickness rat burn wounds." Burns 1991. PMID: 2031672

[53] Karlsson M, Steinvall I, Sjöberg F, et al. "Burn scar outcome at six and 12 months after injury in children with partial thickness scalds: Effects of dressing treatment." Burns 2020. PMID: 32165027

[54] Gee Kee EL, Kimble RM, Cuttle L, et al. "Scar outcome of children with partial thickness burns: A 3 and 6 month follow up." Burns 2016. PMID: 26546385

[55] Barrett JP, Raby E, Wood F, et al. "An in vitro study into the antimicrobial and cytotoxic effect of Acticoat™ dressings supplemented with chlorhexidine." Burns 2022. PMID: 34649749

[56] McManus AT, Denton CL, Mason AD, et al. "Topical chlorhexidine diphosphanilate (WP-973) in burn wound sepsis." Arch Surg 1984. PMID: 6421265

[57] Moreira SS, Camargo MC, Caetano R, et al. "Efficacy and costs of nanocrystalline silver dressings versus 1% silver sulfadiazine dressings to treat burns in adults in the outpatient setting: A randomized clinical trial." Burns 2022. PMID: 34688520

[58] Sheckter CC, Meyerkord NL, Sinskey YL, et al. "The Optimal Treatment for Partial Thickness Burns: A Cost-Utility Analysis of Skin Allograft vs. Topical Silver Dressings." J Burn Care Res 2020. PMID: 32043154

[59] Liao ZJ, Huan JN, Lv GZ. "Multi-center clinical study of the effect of silver nitrate ointment on the partial-thickness burn wounds." Zhonghua Shao Shang Za Zhi 2006. PMID: 17285717

[60] Caruso DM, Foster KN, Hermans MH, et al. "Aquacel Ag in the management of partial-thickness burns: results of a clinical trial." J Burn Care Rehabil 2004. PMID: 14726745

[61] Wasiak J, Cleland H, Campbell F. "Dressings for superficial and partial thickness burns." Cochrane Database Syst Rev 2013. PMID: 23543513

[62] Nherera L, Trueman P, Roberts C. "Silver delivery approaches in the management of partial thickness burns: A systematic review and indirect treatment comparison." Wound Repair Regen 2017. PMID: 28742235

[63] Aziz Z, Abu SF, Chong NJ. "A systematic review of silver-containing dressings and topical silver agents (used with dressings) for burn wounds." Burns 2012. PMID: 22030441

[64] Vloemans AF, Hermans MH, van der Wal MB. "Optimal treatment of partial thickness burns in children: a systematic review." Burns 2014. PMID: 24290852

[65] Gravante G, Caruso R, Sorge R. "Nanocrystalline silver: a systematic review of randomized trials conducted on burned patients and an evidence-based assessment of potential advantages over older silver formulations." Ann Plast Surg 2009. PMID: 19571738

[66] Maciel ABDS, Ortiz JF, Siqueira BS. "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. PMID: 31090826

[67] Bailey JK, Sammet S, Overocker J. "MRI compatibility of silver based wound dressings." Burns 2018. PMID: 29921487