Evaluating the Efficacy, Safety, and Tolerance of Silver Sulfadiazine Dressings Once Daily Versus Twice Daily in the Treatment of Burn Wounds.

Topical silver sulfadiazine (SSD) is an effective antimicrobial therapy used to prevent burn wound infection and promote healing, but the frequency of application has not been previously examined. This study compares once versus twice daily dressing changes with SSD, focusing on development of wound infections, incidence of hospital acquired complications, patient pain scores, and length of stay. The objective of this study was to evaluate whether a once-daily or twice-daily application of SSD impacts burn wound healing outcomes. Our institution maintained a twice-daily dressing change standard of care until January 1, 2019. Patients admitted after that date had their dressing changed once daily. We performed a noninferiority analysis which indicated that a sample size of 75 per group would be sufficient to detect a significant difference with a power of 0.80. Our goal is to review outcomes for 75 patients before the change-of-practice and 75 patients after. Our main outcomes recorded are wound infection, average pain scores, average daily narcotic requirements, and length-of-stay. Results from 75 pre-change-of-practice and 75 post-change-of-practice patients showed slightly better outcomes in the post-change-of-practice group. The wound-infection rates were the same for both groups (pre = 5.33%, post = 5.33%), average daily pain levels for the pre-change group were slightly higher but the difference was negligible and not statistically significant (pre = 5.27, post = 5.25), hospital-related complication rates (unrelated to wound care) were higher pre-change (pre = 10.67%, post = 6.67%), and length-of-stay, was longer in the pre-change group (pre = 11.97, post = 10.31). The amount average amount of SSD (g/day) used per patient per hospital stay was higher as well (pre = 320.14, post = 202.12). Further statistical analysis of the results, particularly in the distribution of burn type, age, and burn depth showed no discrepancy and a generalized decreased length-of-stay with once-daily SSD dressing change. Our results show that once-daily dressing changes of SSD in burn wounds have no negative impact on wound outcomes. However, it is associated with a decreased length-of-stay, decreased pain levels, and less hospital-acquired complications. A decreased length-of-stay means reduced medical expenses for the patient and the hospital. In addition, less hospital-acquired complications result in better patient recovery. Since the difference in wound outcomes is negligible and statistically insignificant, changing the standard-of-care to once daily could prove beneficial.

Silver Sulfadiazine and Cerium Nitrate in Ischemic Skin Necrosis of the Leg and Foot: Results of a Prospective Randomized Controlled Study.

Flammacerium is a topical treatment composed of silver sulfadiazine and cerium nitrate initially used in burns. The objective was to assess the effectiveness of silver sulfadiazine and cerium nitrate on ischemic necrosis wounds of the lower limb as an alternative to amputation for a period of 12 weeks. Patients were prospectively randomized to receive silver sulfadiazine and cerium nitrate or standard care. Patients included adults with an ischemic wound of the lower limb, with necrosis covering over at least 50%. Critical ischemia limb was confirmed by an ankle-brachial index <0.7 or >1.3 with radiological confirmation. Patient demographic data, amputations procedures, wound area, Visual Analogue Scale pain rating, clinical infection, and adverse events were recorded. Fifty patients, 34 males and 16 females, were recruited between January 2010 and April 2014, 25 in each group. The mean age was 75.14 years (±11.64). Nine amputations (36%) occurred in each group. Amputation-free survival was superior in the active treatment group versus the standard group (169 393 days, 95% confidence interval = 134.926-203.861, vs 169 393 days, 95% confidence interval = 134.926-203.861). It was not statistically significant (log-rank, P = .958). Wound area reduction between both groups was not statistically different ( P = .651). Less adverse events of the lower limb occurred in the active treatment group ( P = .001). Our study showed that silver sulfadiazine and cerium nitrate is not inferior to standardized care on ischemic necrotic wounds of the lower extremity. Further studies are still needed to confirm its effectiveness.

Safety profile of silver sulfadiazine-bFGF-loaded hydrogel for partial thickness burn wounds.

In the present investigation, the safety of novel combinational silver sulfadiazine-bFGF-loaded hydrogel was assured by performing acute skin irritation, sensitization, acute dermal toxicity, and eye irritation in compliance with the Organization for Economic Co-operation and Development guidelines. In the skin irritation study, placebo, test, and positive control (0.8% w/v aqueous solution of formaldehyde) were applied on New Zealand rabbits and monitored for abnormal skin responses including erythema and edema. The placebo and test formulation did not induce any adverse reactions and were classified as nonirritating materials. In the skin sensitization test, guinea pigs were sensitized by positive control (0.1% w/v 1-chloro-2,4-dinitrobenzene in 10% of propylene glycol as a standard skin sensitizing agent), placebo, and test formulations. Weak sensitization was observed in the placebo and test formulation treated groups. Additionally, acute dermal toxicity test was performed in Wistar rats, where no signs of toxicity were observed in biochemical, hematological, and histopathological studies. Moreover, the acute eye irritation test was carried out in rabbits and no abnormal clinical signs were evident in the cornea or iris. As a whole, these findings suggest that the hydrogel formulation does not cause any skin irritation, skin sensitizationand dermal toxic effects, and eye irritation following dermal and ocular applications, respectively. Therefore, all the findings obtained from this preclinical study indicated that this hydrogel formulation is nontoxic and safe for use in animal models.

Silver Sulfadiazine Retards Wound Healing and Increases Hypertrophic Scarring in a Rabbit Ear Excisional Wound Model.

This study evaluated the effects of topical use of silver sulfadiazine cream (SSD) on wound healing and subsequent scarring in a rabbit ear wound model. Seven millimeter full-thickness excisional wounds were created in rabbit ears. Twenty-four rabbits were randomized into four groups in which each group received base cream, 0.01% SSD, 0.1% SSD, or 1% SSD, respectively. Each treatment was applied at 2-day intervals from postoperative days (PODs) 2 to 14. At POD 7, half of the rabbits from each group were killed and tissues were harvested to measure wound healing parameters that included epithelial gap and granulation area. At POD 28, the remaining rabbits from each group were assessed for hypertrophic scarring. Epithelial gaps in SSD-treated groups at concentrations of 0.1 and 1% were significantly larger than those of base cream-treated controls. In contrast, analysis of granulation areas that represent volume of granulation tissue formed during healing did not show any statistical differences between the base cream-treated group and all three SSD-treated groups. At POD 28, when compared to the base cream-treated group (1.44 ± 0.03), SSD-treated-groups (0.1 and 1%) had more (P < .05) hypertrophic scar formation (scar elevation index = 1.65 ± 0.04, 0.1%; 1.63 ± 0.06, 1%). The results of this study demonstrate that SSD treatment contributes not only to impaired reepithelialization but also to a greater hypertrophic scar formation. These results also indicate that caution should be exercised when using SSD clinically to prevent or treat wound infections.

The effects of Arnebia euchroma ointment on second-degree burn wounds: a randomized clinical trial.

ETHNOBOTANICAL RELEVANCE: Burn injuries can cause detrimental long-term consequences and call for immediate management. Avicenna's Canon of Medicine, describing the use of Abu-Khalsa (Arnebia euchroma) (AE) as being effective for burn healing. The purpose of this study was to evaluate the healing effects of AE ointment (AEO) on patients with a second-degree burn wound and compare its results with silver sulfadiazine cream (SSD). MATERIALS AND METHODS: In this prospective, single-blind clinical trial, 45 patients with similar types of second-degree burns at two different sites of the body were randomly assigned to the two treatment groups. One burn wound site of the patient was treated with SSD and another similar burn wound site with AEO once a day until complete healing was achieved. Wound size and percentage of wound healing were evaluated at 15 days. Satisfaction, clinical adverse events such as pain, burning, warming, erythema, edema, infection, inflammation, and general wound area were assessed on a visual analogue scales, and 6-point scales. RESULTS: The healing time was significantly shorter in the site treated with AEO than SSD (13.9±5.3 vs. 17.5±6.9 days, respectively). The severity of pain and burning were reduced in the AEO site compared with SSD site at the time of dressing change, while the warming score was significantly higher in the AEO wound area. Side-effects were lower in the site treated with AEO. CONCLUSION: In this clinical study, we demonstrated that AEO has benefits over SSD in the treatment of second-degree burn wounds and wound healing and is a viable medication for the management of second-degree burns.

Clinical effectiveness, quality of life and cost-effectiveness of Flaminal® versus Flamazine® in the treatment of partial thickness burns: study protocol for a randomized controlled trial.

BACKGROUND: Partial thickness burns are painful, difficult to manage and can have a negative effect on quality of life through scarring, permanent disfigurement and loss of function. The aim of burn treatment in partial thickness burns is to save lives, stimulate wound healing by creating an optimumly moist wound environment, to have debriding and analgesic effects, protect the wound from infection and be convenient for the patient and caregivers. However, there is no consensus on the optimal treatment of partial thickness wounds. Flaminal® and Flamazine® are two standard treatment options that provide the above mentioned properties in burn treatment. Nevertheless, no randomized controlled study has yet compared these two common treatment modalities in partial thickness burns. Thus, the aim of this study is to evaluate the clinical effectiveness, quality of life and cost-effectiveness of Flaminal® versus Flamazine® in the treatment of partial thickness burns. METHODS/DESIGN: In this two-arm open multi-center randomized controlled trial, 90 patients will be randomized between Flaminal® and Flamazine® and followed for 12 months. The study population will consist of competent or temporarily non-competent (because of sedation and/or intubation) patients, 18 years of age or older, with acute partial thickness burns and a total body surface area (TBSA) of less than 30 %. The main study outcome is time to complete re-epithelialization (greater than 95 %). Secondary outcome measures include need for grafting, wound colonization/infection, number of dressing changes, pain and anxiety, scar formation, health-related quality of life (HRQoL), and costs. DISCUSSION: This study will contribute to the optimal treatment of patients with partial thickness burn wounds and will provide evidence on the (cost-)effectiveness and quality of life of Flaminal® versus Flamazine® in the treatment of partial thickness burns. TRIAL REGISTRATION: Netherlands Trial Register NTR4486 , registered on 2 April 2014.

[Investigation of antibacterial activity of topical antimicrobials against methicillin-resistant Staphylococcus aureus].

OBJECTIVE: To investigate the antibacterial activity of silver sulfadiazine (SD-Ag), mupirocin, and clotrimazole used alone or in combination against methicillin-resistant Staphylococcus aureus (MRSA) isolated from burn wounds. METHODS: Eighteen MRSA isolates from wound excretion of 18 burn patients hospitalized in our unit from July to December 2011 were collected continuously and non-repetitively. (1) Minimum inhibitory concentration (MIC), 50% MIC (MIC50), and 90% MIC (MIC90) of SD-Ag, mupirocin, and clotrimazole used alone, those of SD-Ag and mupirocin used in combination, and those of SD-Ag, mupirocin, and clotrimazole used in combination to MRSA were determined by checkerboard agar dilution method. (2) Fractional inhibitory concentration (FIC) index was calculated to determine the combined effect of SD-Ag plus mupirocin, and SD-Ag plus mupirocin and clotrimazole. Synergy with FIC index less than or equal to 0.5 or additivity with FIC index more than 0.5 and less than or equal to 1.0 was regarded as effective, and indifference with FIC index more than 1.0 and less than or equal to 4.0 or antagonism with FIC index more than 4.0 was regarded as ineffective. The effective ratio was compared with overall ratio (assumed as 0) by unilateral binomial distribution test. RESULTS: The MIC, MIC50, and MIC90 of SD-Ag, mupirocin, and clotrimazole used alone against 18 MRSA isolates were respectively 8, 8, 16 µg/mL; 2, 16, 64 µg/mL; 2, 2, 2 µg/mL. MIC of antimicrobial agents used in combination decreased from 3.1% to 50.0% as compared with that of individual agent used alone. Compared with those of single application of SD-Ag and mupirocin, MIC50 of SD-Ag and that of mupirocin both decreased 75.0%, and MIC90 of them decreased 87.5% when SD-Ag and mupirocin were used in combination. Compared with those of single application of SD-Ag, mupirocin, and clotrimazole, MIC50 of SD-Ag, mupirocin, and clotrimazole respectively decreased 75.0%, 87.5%, and 50.0%; MIC90 of them respectively decreased 87.5%, 96.9%, and 50.0% when SD-Ag, mupirocin, and clotrimazole were used in combination. Among the 18 MRSA isolates, the combined effect of SD-Ag and mupirocin was synergic in 9 isolates, additive in 7 isolates, indifferent in 2 isolates, and antagonistic in 0 isolate; the combined effect of SD-Ag, mupirocin, and clotrimazole was additive in 16 isolates, indifferent in 2 isolates, and antagonistic in 0 isolate. There were statistically significant differences between effective ratio and overall ratio of 18 MRSA isolates treated with combined antimicrobial agents (P values all above 0.01). CONCLUSIONS: For burn wounds at middle and late stages infected with Staphylococcus aureus or Staphylococcus aureus and Fungus, low dose of SD-Ag or combination of above-mentioned antimicrobial agents can effectively control infection and decrease the adverse effect of antimicrobial agents on wound healing.

Antibiotic prophylaxis for preventing burn wound infection.

BACKGROUND: Infection of burn wounds is a serious problem because it can delay healing, increase scarring and invasive infection may result in the death of the patient. Antibiotic prophylaxis is one of several interventions that may prevent burn wound infection and protect the burned patient from invasive infections. OBJECTIVES: To assess the effects of antibiotic prophylaxis on rates of burn wound infection. SEARCH METHODS: In January 2013 we searched the Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE - In-Process & Other Non-Indexed Citations (2013); Ovid EMBASE; EBSCO CINAHL and reference lists of relevant articles. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: All randomised controlled trials (RCTs) that evaluated the efficacy and safety of antibiotic prophylaxis for the prevention of BWI. Quasi-randomised studies were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed the risk of bias, and extracted relevant data. Risk ratio (RR) and mean difference (MD) were estimated for dichotomous data and continuous data, respectively. When sufficient numbers of comparable RCTs were available, trials were pooled in a meta-analysis to estimate the combined effect. MAIN RESULTS: This review includes 36 RCTs (2117 participants); twenty six (72%) evaluated topical antibiotics, seven evaluated systemic antibiotics (four of these administered the antibiotic perioperatively and three administered upon hospital admission or during routine treatment), two evaluated prophylaxis with non absorbable antibiotics, and one evaluated local antibiotics administered via the airway.The 11 trials (645 participants) that evaluated topical prophylaxis with silver sulfadiazine were pooled in a meta analysis. There was a statistically significant increase in burn wound infection associated with silver sulfadiazine compared with dressings/skin substitute (OR = 1.87; 95% CI: 1.09 to 3.19, I(2) = 0%). These trials were at high, or unclear, risk of bias. Silver sulfadiazine was also associated with significantly longer length of hospital stay compared with dressings/skin substitute (MD = 2.11 days; 95% CI: 1.93 to 2.28).Systemic antibiotic prophylaxis in non-surgical patients was evaluated in three trials (119 participants) and there was no evidence of an effect on rates of burn wound infection. Systemic antibiotics (trimethoprim-sulfamethoxazole) were associated with a significant reduction in pneumonia (only one trial, 40 participants) (RR = 0.18; 95% CI: 0.05 to 0.72) but not sepsis (two trials 59 participants) (RR = 0.43; 95% CI: 0.12 to 1.61).Perioperative systemic antibiotic prophylaxis had no effect on any of the outcomes of this review.Selective decontamination of the digestive tract with non-absorbable antibiotics had no significant effect on rates of all types of infection (2 trials, 140 participants). Moreover, there was a statistically significant increase in rates of MRSA associated with use of non-absorbable antibiotics plus cefotaxime compared with placebo (RR = 2.22; 95% CI: 1.21 to 4.07).There was no evidence of a difference in mortality or rates of sepsis with local airway antibiotic prophylaxis compared with placebo (only one trial, 30 participants). AUTHORS' CONCLUSIONS: The conclusions we are able to draw regarding the effects of prophylactic antibiotics in people with burns are limited by the volume and quality of the existing research (largely small numbers of small studies at unclear or high risk of bias for each comparison). The largest volume of evidence suggests that topical silver sulfadiazine is associated with a significant increase in rates of burn wound infection and increased length of hospital stay compared with dressings or skin substitutes; this evidence is at unclear or high risk of bias. Currently the effects of other forms of antibiotic prophylaxis on burn wound infection are unclear. One small study reported a reduction in incidence of pneumonia associated with a specific systematic antibiotic regimen.

Toxic megacolon from fulminant Clostridium difficile infection induced by topical silver sulphadiazine.

Pseudomembranous colitis and toxic megacolon (TM) are well-known complications of Clostridium difficile infections. Systemic antibiotic is considered as the major risk factor for the development of C difficile colitis. However, topical antibiotics are rarely associated with the infection. As previously thought, the use of topical antibiotic is capable of systemic absorption in damaged and denuded skin; sufficient enough to suppress the normal bowel flora. Here, we present an unusual case of TM from C difficile infection induced by topical silver sulphadiazine in a 60-year-old man with immune-bullous pemphigus vulgaris. The diagnosis is further complicated by the absence of diarrhoea as the initial presentation. Despite adequate medical and surgical intervention, the patient had an unfavourable outcome.

Nanoscalic silver possesses broad-spectrum antimicrobial activities and exhibits fewer toxicological side effects than silver sulfadiazine.

Silver has been used successfully for decades as an antibacterial agent and has become a standard treatment for burns and bacterial skin infections. Silver-containing creams, particularly silver sulfadiazine (SSD), possess effective activities against bacteria and fungi. However, there is serious concern that silver ions applied to denuded skin might be absorbed in significant amounts, thus introducing the risk of silver deposition, potentially leading to internal organ injury. In view of these facts we compared the percutaneous absorption and the antimicrobial potency of SSD with a new composition, nanoscalic silver (NSAg). In a murine model topical application of NSAg resulted in significantly lower percutaneous absorption and internal organ deposition compared to SSD. Strikingly, antimicrobial activity of NSAg used as a 0.1% formulation was comparable not only with 0.1% SSD against different bacterial strains including methicillin-resistant Staphylococcus aureus, but also against different yeast and dermatophyte species. FROM THE CLINICAL EDITOR: Nanoscale silver (NSAg) was demonstrated to have significantly lower percutaneous absorption and less accumulation in multiple organs when applied to denuded skin. Its antimicrobial activity against MRSA was not only comparable to silver sulfadiazine, but the formulation was also effective against different yeast and dermatophyte species.

An open, parallel, randomized, comparative, multicenter study to evaluate the cost-effectiveness, performance, tolerance, and safety of a silver-containing soft silicone foam dressing (intervention) vs silver sulfadiazine cream.

An open, parallel, randomized, comparative, multicenter study was implemented to evaluate the cost-effectiveness, performance, tolerance, and safety of a silver-containing soft silicone foam dressing (Mepilex Ag) vs silver sulfadiazine cream (control) in the treatment of partial-thickness thermal burns. Individuals aged 5 years and older with partial-thickness thermal burns (2.5-20% BSA) were randomized into two groups and treated with the trial products for 21 days or until healed, whichever occurred first. Data were obtained and analyzed on cost (direct and indirect), healing rates, pain, comfort, ease of product use, and adverse events. A total of 101 subjects were recruited. There were no significant differences in burn area profiles within the groups. The cost of dressing-related analgesia was lower in the intervention group (P = .03) as was the cost of background analgesia (P = .07). The mean total cost of treatment was $309 vs $513 in the control (P < .001). The average cost-effectiveness per treatment regime was $381 lower in the intervention product, producing an incremental cost-effectiveness ratio of $1688 in favor of the soft silicone foam dressing. Mean healing rates were 71.7 vs 60.8% at final visit, and the number of dressing changes were 2.2 vs 12.4 in the treatment and control groups, respectively. Subjects reported significantly less pain at application (P = .02) and during wear (P = .048) of the Mepilex Ag dressing in the acute stages of wound healing. Clinicians reported the intervention dressing was significantly easier to use (P = .03) and flexible (P = .04). Both treatments were well tolerated; however, the total incidence of adverse events was higher in the control group. The silver-containing soft silicone foam dressing was as effective in the treatment of patients as the standard care (silver sulfadiazine). In addition, the group of patients treated with the soft silicone foam dressing demonstrated decreased pain and lower costs associated with treatment.

Incidence of methemoglobinemia in patients receiving cerium nitrate and silver sulfadiazine for the treatment of burn wounds: a burn center's experience.

In 1976, the combination of cerium nitrate and silver sulfadiazine was introduced as a topical therapy for burn wounds. Experience with a locally prepared combination agent has shown physical change of the eschar and delayed subeschar bacterial colonization. A potential systemic complication of this treatment is the development of methemoglobinemia (Met-Hba) due to the oxidizing nature of Ce(NO(3))(3). Met-Hba has a spectrum of clinical consequences, ranging from headache and cyanosis to cardiac ischemia, hypotension, and even death. Given the frequent use of this combination agent at our burn center, a retrospective review was conducted to evaluate the incidence of Met-Hba. A query of pharmacy records revealed 170 patients from January 2005 to October 2009 that had received this treatment. Eighteen patients (∼10%) developed Met-Hba as noted on arterial blood gas (methemoglobin>3%) and only three patients (∼2%) had methemoglobin levels >10%. In the majority of cases, there were no clinical symptoms of Met-Hba. Most patients' relative hypoxia resolved with cessation of treatment; however, five patients required treatment with methylene blue. The presence of Met-Hba associated with this topical therapy can be diagnosed early by vigilant monitoring, thereby reducing morbidity and mortality. In our experience, cerium combined with silver sulfadiazine is a valuable and safe treatment for deep partial and full-thickness burn wounds.

Conservative management of exomphalos major with silver dressings: are they safe?

Historically, some dressings used in exomphalos major were associated with toxicity. These have been abandoned in favor of safer dressings. Silver toxicity has not been described following the use of silver dressings in infants. We, however, found disconcerting serum silver levels in 2 consecutive patients during treatment with silver salt containing dressings.