Silver sulfadiazine-cerium nitrate burn wound foam dressing stabilizes eschar by reducing local inflammation and controlling burn wound infections.

It was often uncertain whether antiseptics were associated with any difference in healing, infections, or other outcomes. Where there is moderate or high certainty evidence, decision makers need to consider the applicability of the evidence from the comparison to their patients. Reporting was poor, to the extent that we are not confident that most trials are free from risk of bias.

A synergistic effect between cerium nitrate and silver sulphadiazine

An open study comparing topical silver sulfadiazine and topical silver sulfadiazine–cerium nitrate in the treatment of moderate and severe burns

Significance: The standard of care for deep burn wounds is eschar excision and autologous skin grafting within the first postburn days. However, when this is not practical due to medical reasons, unavailable surgical facilities, or lack of donor sites or other coverage, surgeons have used topical cerium nitrate (CN) in a cream with silver sulfadiazine (SSD) for over four decades to convert the eschar into a pliable and protective crust that facilitates the postponement or staging of eschar excision and grafting. CN+SSD treatment is reported to reduce dressing changes, improve patient comfort, and reduce bacterial burden, with unaffected epithelialization and few complications. Recent Advances: CN aqueous solutions applied topically alone or together with solid silver dressings in animal models have mitigated wound injury progression, wound microbial burden, and systemic immune dysfunction. Critical Issues: CN+SSD cream is not approved by U.S. Food and Drug Administration (FDA) and its efficacy in clinical trials has been challenging to demonstrate. One reason is that CN changes the eschar visibly, introducing unavoidable bias. Also, the market and patient population is small and burn wound presentation is highly variable. Future Directions: For use in settings wherein the once- or twice-daily CN+SSD cream dressing changes are least feasible (low-income, military, and mass casualty settings), it may be possible to develop a solid dressing containing cerium and silver that requires infrequent dressing changes. For future clinical studies, the trial design most suited to comparing silver-containing dressings with and without cerium may be paired difference of matched intrapatient wounds.

The randomised controlled trial data on the effectiveness and safety of topical antimicrobial treatments for diabetic foot ulcers is limited by the availability of relatively few, mostly small, and often poorly designed trials. Based on our systematic review and analysis of the literature, we suggest that: 1) use of an antimicrobial dressing instead of a non-antimicrobial dressing may increase the number of diabetic foot ulcers healed over a medium-term follow-up period (low-certainty evidence); and 2) there is probably little difference in the risk of adverse events related to treatment between systemic antibiotics and topical antimicrobial treatments based on the available studies (moderate-certainty evidence). For each of the other outcomes we examined there were either no reported data or the available data left us uncertain as to whether or not there were any differences between the compared treatments. Given the high, and increasing, frequency of diabetic foot wounds, we encourage investigators to undertake properly designed randomised controlled trials in this area to evaluate the effects of topical antimicrobial treatments for both the prevention and the treatment of infection in these wounds and ultimately the effects on wound healing.

Burns injuries during pregnancy are rarely reported in developed countries, but an increasing in mortality and morbidity has been observed. The authors describe their experience in the treatment of pregnant women in a burn unit. A 12-year retrospective study of burns in pregnant women hospitalized was conducted. Since 2008, two pregnant women were admitted in their unit. Patient 1, a 32-year-old pregnant woman on second trimester (27s6d), suffered a second-degree burn injury, 16% total body surface area (TBSA), caused by fire. She was admitted in their burn unit and submitted to medical treatment, wound dressing, and surgical treatment. Cerium nitrate and silver sulfadiazine were used in burn lesions and the patient was submitted to debridement and skin graft surgery. No uneventful events occurred with the fetus. Patient 2 was a 32-year-old pregnant woman on second trimester (26s), HVC positive, admitted with a second-degree flash burn, 8% TBSA. She was submitted to endotracheal intubation before arriving to the hospital due to risk of airway burn. Dexamethasone was administered for fetus lung maturation. No uneventful events were observed. The incidence of thermal injury in pregnancy in Portugal is low. Active medical treatment together with conservative wound care should be the standard in each trimester of pregnancy. Although there is limited safety information on cerium nitrate or silver sulfadiazine during pregnancy, those were used with no adverse effects on one of their patients. Obstetrical management should be individualized.

Introduction: Thermal burns account for 5-10% of casualties sustained in present-day conflicts and are expected to be one of the most common wounds to occur in future conflicts. Timely debridement of necrotic burn tissue can greatly reduce the chances of mortality and late-stage complications. However, future conflicts are anticipated to occur in austere environments where surgical debridement may not be plausible and casualty evacuations significantly delayed. Without access to prompt surgical interventions and standard treatment, burn wounds can progress (become deeper and more extensive) and become highly susceptible to infection. Several studies have demonstrated that topical applications of Cerium (III) Nitrate (Cen) can be used to delay the need for surgical eschar removal, a delay which may be forced upon injured warfighters in austere environments. The proof-of-concept studies described herein suggest that an electrospun dressing with a Polyethylene Oxide (PEO) shell and CeN core could prolong the time before surgical intervention is required and/or mitigate late-stage burn pathophysiologies in Prolonged Field Care (PFC) scenarios. Materials and Methods: Coaxially electrospun PEO dressings with a CeN payload were synthesized for application in a swine burn model. Dressings were first evaluated ex vivo using a Lactate Dehydrogenase (LDH) assay to confirm that no cytotoxic effects were present. Then, one female Yorkshire pig was anesthetized and received ten 5 cm x 5 cm contact burns with a brass burn device that was heated to 100°C. The deep-partial thickness wounds were randomly assigned to one of five treatment groups: 1) 1-Layer of the PEO/CeN dressing, 2) 4-Layers of the PEO/CeN dressing, 3) 4-layers of a control electrospun PEO dressing, 4) Flammacerium® cream (silver sulfadiazine 1%, cerium nitrate 2.2%), or 5) the PFC standard of care (SOC; gauze). Wounds were observed over an 18-day period, with surgical debridement occurring on Day 4 for all wounds. Transepidermal water loss, depth to debridement, and histologic measurements of necrosis were utilized to assess the burns. Research was conducted in compliance with the Animal Welfare Act, the implementing Animal Welfare regulations, and the principles of the Guide for the Care and Use of Laboratory Animals, National Research Council. The facility’s Institutional Animal Care and Use Committee approved all research conducted in this study. The facility where this research was conducted is fully accredited by AAALAC International. Experimental design and statistical comparisons were approved by an accredited epidemiologist and biostatistician. Results: The PEO/CeN dressings did not elicit a cytotoxic response ex vivo. Compared to the PFC SOC, treatments containing CeN reduced the amount of necrotic tissue produced by second-degree thermal injuries, as evidenced both histologically and in the depth required to reach viable tissue during surgical debridement. Importantly, the dressing did not adversely impact the live tissue surrounding the burn site. Conclusions: There are currently no field dressings that can delay the need for immediate debridement and thereby promote burn wound healing. This proof-of-concept study strongly suggests that the electrospun PEO/CeN dressing could fulfill this unmet medical need and advocates for further evaluation for use in imminent PFC scenarios.

Silver sulfadiazine is a topical antibiotic helps to prevent and treat wound infections in patients with severe burns. This research was performed to evaluate the impact of the Trivedi Effect®- Consciousness Energy Healing Treatment on the structural properties and the isotopic abundance ratio of silver sulfadiazine using spectroscopic and chromatographic techniques. The test sample silver sulfadiazine sample was divided into control and treated parts. Only the treated part of silver sulfadiazine was received the Trivedi Effect®-Consciousness Energy Healing Treatment remotely by a renowned Biofield Energy Healer, Dahryn Trivedi. The LC-MS spectra of both the samples at retention time (Rt ) 4.1 minutes exhibited the mass of the protonated molecular ion peak at m/z 251.08 (calculated for C10H11N4 O2 S+ , 251.06) was found to be sulfadiazine. The chromatographic peak area of the treated silver sulfadiazine was significantly increased by 20.35% compared to the control sample. The result indicated that the solubility profile of the treated silver sulfadiazine must have increased significantly after the Biofield Energy Treatment compared with the control sample. The LC-MS based isotopic abundance ratio of PM+1/PM in the treated sulfadiazine was significantly increased by 31.88% compared with the control sample. Similarly, the GC-MS based isotopic abundance ratio of PM+1/PM and PM+2/PM in the treated sulfadiazine was significantly increased by 9.74% and 15.13%, respectively compared with the control sample. Hence, 13C, 2 H, 15N, 17O, 33S, and 34S contributions from (C7 H9 N2 O2 S)+ to m/z 186 and 187 in the treated sulfadiazine were significantly increased compared to the control sample. Thus, the isotopic abundance ratios of PM+1/PM (2 H/1 H or 13C/12C or 15N/14N or 17O/16O or 33S/32S) and PM+2/PM (34S/32S) in the treated sulfadiazine were significantly increased compared to the control sample. The changes in isotopic abundance and peak area might be due to changes in nuclei possibly via the interference of neutrino particles controlled by the Trivedi Effect®-Consciousness Energy Healing Treatment. The increased isotopic abundance ratio of the treated silver sulfadiazine might improve the chemical bond strength, led to increase the stability in the body. This novel silver sulfadiazine would be more efficacious in pharmaceutical formulations which might offer better solubility, bioavailability, and therapeutic response against bacterial infections, superficial and partial thickness burn injuries, etc.

Previous studies have indicated that combining cerium nitrate with silver sulfadiazine (Silvadene, Marion Labs) yields a superior topical agent for the treatment of burns. Cerium nitrate in silver sulfadiazine was tested in a controlled study with silver sulfadiazine alone. The study population consisted of two groups of children suffering burns greater than 30% of the body surface. The patients ranged in size from 1 to 21 years. The study period was for the first 10 weeks of hospitalization. Quantitative surface cultures were used to monitor burn wound flora. No superiority for the silver sulfadiazine-cerium nitrate combination was demonstrated. In fact, cultures indicate a significantly greater percentage of Gram-negative pathogens in patients treated with the cerium mixture. Cerium nitrate could possibly prove of greatest benefit if used as a reserve therapy for colonizing organisms which do not routinely respond to silver sulfadiazine.

Silver sulfadiazine (SSD), a topical antimicrobial agent, has been widely used for the prophylaxis and treatment of burn infections during the past 30 years. We determined the antimicrobial activity of SSD, alone and in combination with cerium nitrate (CN), gentamicin and amikacin against 130 recent clinical isolates, including multiresistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. The overall activity of SSD was good against all the tested strains and it was particularly high against MRSA (MIC90 100 μg/ml). CN showed no inhibitory effect, even up to 800 μg/ml, on bacterial strains tested. The combination of SSD and CN was as active as SSD alone. In conclusion, SSD has a broad spectrum of activity at concentrations lower than those commonly used in clinical preparations. All strains were inhibited by less then one-fiftieth of the SSD “in use” concentration (10 mg/ml). Our data confirm the efficacy of this topical agent in the prevention and treatment of infections in burns or other surgical wounds and suggest its possible use in clearing staphylococcal carriage as an alternative to mupirocin.

Control of infection in major burn wounds by cerium nitrate/silver sulphadiazine

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.

Because burns damage skin leaving patients particularly susceptible to infection, various topical antimicrobial treatments have been developed to control the proliferation of microorganisms on the burn wound. One treatment used in our burn unit is a 3:1 mixture of 500U/g bacitracin (B) and 1% silver sulfadiazine (SSD). This topical agent needs to be mixed immediately prior to use. Recently, a ready-made, sustained-release, silver-containing hydrogel, SilvaSorb™ (S-Gel), became commercially available. The purpose of this study was to compare 1) the cost, and 2) the in-vitro efficacy of the B+SSD mixture to S-Gel. An agar well diffusion assay was used to determine the susceptibility of the microbes to the topical agents. Because bacitracin ointment does not diffuse out of the agar wells, an aqueous solution of bacitracin at the concentration in the ointment was used in these tests. Fifty-nine microorganisms commonly isolated from burn patients were tested: 10 yeasts, 10 molds, 19 gram-positive bacteria, and 20 gram-positive bacteria.

Cerium nitrate in the management of burns

The synthetic antimicrobial peptide SAAP-148 was found to be effective against a wide range of (antimicrobial-resistant) gram-positive and gram-negative bacteria, in vitro and in a superficial skin infection model in mice, but not a surgical wound infection model in rats. In addition, the efficacy of SAAP-148 in protein-rich environments such as blood plasma and eschar extract is considerably reduced as compared to PBS. The aim of the present study is to determine which wound-related factors reduce SAAP-148’s efficacy. As high dosages of SAAP-148 may be required in infected wounds we also assessed the in vitro and ex vivo cytotoxicity of SAAP-148. Preincubation of SAAP-148 in 50% (v/v) blood plasma or eschar extract for 24 h, 3% (v/v) bovine serum albumin or a collagen-elastin 3D matrix significantly reduced the bactericidal efficacy of the peptide. Also, the presence of protease inhibitors did not restore the bioactivity of SAAP-148, suggesting a reduced bioavailability of SAAP-148 due to protein binding, rather than degradation. Furthermore, relatively low concentrations of SAAP-148 (≥0.23 nmol/100 µl) induced cytotoxicity for human skin cells in 2D culture. Contrarily, SAAP-148 did not induce cytotoxicity for cells in ex vivo human skin. In addition, unlike silver sulfadiazine (SSD), SAAP-148 showed no statistically significant adverse effects on the re-epithelialization of ex vivo excision wounds and burn wounds. Hence, SAAP-148 potentially has a beneficial profile for antimicrobial treatment of infected wounds. Key words: SAAP-148, proteolytic degradation, bioactivity, peptide interaction, cytotoxicity, skin and soft tissue infection.