The effects of topical mafenide acetate application on skin graft survival in bacterial contaminated wounds.

BACKGROUND: Infection related skin graft loss still remains as a common problem even with the use of systemic antibiotics. Mafenide acetate (Sulfamylon) is a topical antimicrobial agent with a wide spectrum of antimicrobial activity. Since mafenide acetate has the ability to penetrate the burn eschar, it was preferred in the treatment of infected full-thickness skin grafts. We investigated the effects of topical Mafenide acetate application on graft survival in an experimental model of contaminated wound beds in rats. MATERIALS AND METHODS: Twenty-eight male Wistar albino rats were included in the study. A full-thickness skin graft (FTSG) was harvested from the back region and the wound bed was inoculated with Pseudomonas aeruginosa. The same FTSG was sutured in place. Rats were divided into 4 groups. In groups 1 and 2, wound care was performed with gauze and hydrofiber dressings respectively. In groups 3 and 4, Mafenide acetate soaked hydrofiber and Mafenide acetate soaked gauze dressings were used respectively. The dressings were closed for 4 days in all groups. The rats in groups 1 and 2 received dressing changes every day. The dressing of the rats in group 3 was changed once every two days. The dressing of the rats in group 4 was changed twice a day. RESULTS: In groups 3 and 4, the graft survival rates decreased significantly from day 7 to day 14 in all groups. Histologically, detachment at the dermoepidermal junction, disorganization of collagen along with increased numbers of fibroblasts and a decrease in graft adhesion to the wound bed were determined in Mafenide acetate-treated groups. CONCLUSION: In rats treated with Mafenide acetate, graft survival was higher on day 7 and gradually decreased towards day 14. Application of a 2.5% solution of Mafenide acetate longer than 7 days on inoculated skin grafts in a rat model causes significant cytotoxicity and graft loss.

Debridement of Sulfur Mustard Skin Burns: A Comparison of Three Methods.

Sulfur mustard burns are characterized by delayed symptoms, slow healing, and recurrence after closure. Incomplete debridement at the level of the basement membrane is the postulated cause. Graham pioneered laser debridement of mustard burns. For field or mass-casualty use, saline wet-to-wet or antibiotic-soak debridement is more practical. In this study, we compared laser, saline, and antibiotic debridement in a porcine model of deep partial-thickness injury. Deep-dermal sulfur mustard burns were produced in 18 anesthetized Gottingen minipigs using 10-µl saturated vapor cap exposure time of 90 minutes. Debridement was started 48 hours postinjury and consisted of a single laser treatment; 5 days of 5% aqueous mafenide acetate wet-to-wet dressings; or 7 to 12 days of saline wet-to-wet dressings. Wounds were treated with daily silver sulfadiazine for 30 days and, then, assessed by histopathology, silver-ion analysis, colorimetry, and evaporimetry. All wounds healed well with no sign of infection. Antibiotic debridement showed no advantage over saline debridement. There were no significant differences between groups for colorimetry or evaporimetry. Histopathology was graded on a mustard-specific scale of 1 to 15 where higher values indicate better healing. Mean histology scores were 13.6 for laser, 13.9 for mafenide, and 14.3 for saline. Saline debridement statistically outperformed laser (P < .05) but required the longest debridement time. Laser debridement had the benefit of requiring a single treatment rather than daily dressing changes, significantly decreasing need for wound care and personnel resources. Development of a ruggedized laser for field use is a countermeasures priority.

2.5% Mafenide Acetate: A Cost-Effective Alternative to the 5% Solution for Burn Wounds.

Mafenide acetate is an antimicrobial agent used to decrease the bacterial load for burn wounds. The 5% solution is more commonly used yet double the cost of its 2.5% counterpart. This study aims to evaluate outcomes and cost associated with the use of 2.5 vs 5% mafenide acetate formulation in the adult burn population. Adult patients (≥18 years) receiving 2.5% mafenide acetate during an 11-month period between 2014 and 2015, corresponding to a policy change in favor of the use of 2.5% mafenide acetate, were queried. Historical controls, patients receiving 5% mafenide acetate, were also reviewed during an 11-month period between 2013 and 2014. A retrospective review was performed comparing wound infection rate, bacteremia, sepsis, pneumonia, duration of mafenide therapy, length of hospital stay, mortality, and cost. A total of 54 and 65 patients received 2.5 and 5% mafenide acetate, respectively. There was no difference in wound infection, bacteremia, sepsis, pneumonia, duration of treatment, and mortality between the two groups. No adverse events occurred in either group directly related to mafenide. Candida and Staph species were the two most common isolates in the 2.5% group, whereas Pseudomonas and Staph species were the most common in the 5% arm. The mean cost of 2.5% mafenide therapy was $1494.92 compared with $3741.39 for 5% mafenide acetate. The 2.5% concentration demonstrates to be an equally efficacious and cost-effective alternative to the 5% concentration. Burn centers should consider the use of the more dilute preparation for burn wound infection prophylaxis as it may reduce the cost without compromising patient safety.

Hydrofiber Dressing Saturated With Mafenide Acetate Extends the Duration of Antimicrobial Activity.

Mafenide acetate is used in some burn wounds for its ability to penetrate eschar but requires frequent uncomfortable dressing changes for its application. The authors hypothesize that hydrofiber dressings will hold mafenide acetate solution for an extended period of time and maintain antimicrobial activity longer than traditional gauze, thus possibly obviating the need for frequent dressing changes. Four experimental arms included: 1) hydrofiber, stored on a dry well plate as control, 2) gauze saturated with 2.5% mafenide acetate, stored on nonsterile porcine skin, 3) hydrofiber saturated with mafenide acetate, stored on dry well plate, and 4) hydrofiber saturated with mafenide acetate, stored on nonsterile porcine skin. At 0, 24, 48, and 72 hours, a 1-cm disk was cut from the dressing sheet of each study arm, placed on agar plates seeded with Staphylococcus aureus and Pseudomonas aeruginosa, and incubated for 24 hours, and the zone of inhibition was measured. A zone of 2 mm or greater was indicative of susceptibility. Each arm of the experiment was performed four times to demonstrate reproducibility. Plain hydrofiber (control) demonstrated no zone of inhibition at any time point, thereby possessing no antimicrobial activity alone. Gauze saturated with mafenide acetate did not reliably demonstrate antimicrobial activity beyond 0 hours. Hydrofiber saturated with mafenide acetate, whether stored on a dry well plate or nonsterile porcine skin, consistently possessed sustained antimicrobial activity as demonstrated by zones of inhibition greater than 2 mm to both S. aureus and P. aeruginosa. Mafenide acetate-soaked hydrofiber dressings stay moist and maintain antimicrobial activity against S. aureus and P. aeruginosa for at least 72 hours without repeated soaks.

Care of the Burn Casualty in the Prolonged Field Care Environment.

Burns are frequently encountered on the modern battlefield, with 5% - 20% of combat casualties expected to sustain some burn injury. Addressing immediate life-threatening conditions in accordance with the MARCH protocol (massive hemorrhage, airway, respirations, circulation, hypothermia/head injury) remains the top priority for burn casualties. Stopping the burning process, total burn surface area (TBSA) calculation, fluid resuscitation, covering the wounds, and hypothermia management are the next steps. If transport to definitive care is delayed and the prolonged field care stage is entered, the provider must be prepared to provide for the complex resuscitation and wound care needs of a critically ill burn casualty.

The diversity of wound presentation associated with freon contact frostbite injury.

The authors report two cases of patients presenting with chemical frostbite-like injuries to the hands and wrists after contact exposure to Freon liquid. Although the history and initial physical presentations were quite similar, the severity of these injuries varied widely from superficial bullae to deep tissue injuries, requiring skin grafting and amputation of several digits. Freon is a widely used coolant in refrigerators, air conditioners, freezers, and water coolers, with a boiling point of -41°C. Although several cases of Freon-induced inhalational injury have been reported, few case reports of Freon-associated contact skin injury exist in the literature. The authors detail the broad diversity of injuries resulting from Freon contact as well as the first report of severe Freon injury necessitating skin grafting and amputation of multiple digits.

Understanding and managing burn pain: Part 2.

Despite advances in treatment of burn injuries and their consequent pain, wound care is the main source of the pain associated with burn injury. This two-part article explores burn pain and its treatment from a nursing perspective. Last month, Part 1 provided an overview of burn injury and addressed the wound care-related causes of burn pain, as well as its assessment and treatment. Part 2, presented here, provides a more in-depth discussion of pain management; topical medications and the psychological aspects of burn pain are also discussed.

Comparison of therapeutic antibiotic treatments on tissue-engineered human skin substitutes.

For regenerative medicine to gain clinical acceptance, the effects of commonly used treatment regimens on bioengineered organs must be considered. The antibiotics mafenide acetate (mafenide) and neomycin plus polymyxin (neo/poly) are routinely used to irrigate postoperative skin grafts on contaminated wounds. The effects of these clinically used antibiotics were investigated using tissue-engineered human skin substitutes generated with primary human keratinocytes or the near-diploid human keratinocyte cell line, Near-diploid Immortal Keratinocytes. Following topical or dermal treatment, the skin substitutes were assayed for viability, tissue morphology, glycogen content, and the expression of active caspase 3. Mafenide, but not neo/poly, induced morphological and biochemical changes in tissue-engineered skin substitutes. Keratinocytes in all histological layers of mafenide-treated skin substitutes exhibited ballooning degeneration and glycogen depletion. Mafenide-treatment also triggered separation of basal keratinocytes from the underlying dermis. None of the antibiotic treatments induced apoptosis, as measured by active caspase 3 immunostaining. The results demonstrate that mafenide, but not neo/poly, is detrimental to the viability and structural integrity of tissue-engineered human skin substitutes. These findings highlight the need to identify treatment regimens that are compatible with and hence enable the therapeutic efficacy of first-generation bioengineered organs such as skin.

Allergic contact dermatitis to mafenide acetate: a case series and review of the literature.

Burn patients with extensive involvement of body surface area (BSA >30%) represent a challenge in wound treatment. Multiple topical agents may be used for cleansing, barrier protection, and antimicrobial control leading to complications of contact and/or irritant dermatitis, which may further complicate re-epithelization and eventual wound healing. We present 4 patients who sustained extensive burns during Operation Iraqi Freedom/Operation Enduring Freedom and later developed contact dermatitis to mafenide acetate, a common topical antimicrobial used in burn care treatment, also known as Sulfamylon (alpha-amino-p-toluenesulfonamide monoacetate). All patients who were patch tested to mafenide acetate 7% solution were positive. A rechallenge with mafenide acetate resulted in recrudescence of the eruption in 2 out of the 4 patients. Though cutaneous reactions to mafenide acetate were reported by Yaffe and Dressler in 1969, the most recent case reports are from 1995. This paper presents more recent examples of cutaneous reactions to mafenide acetate, while also reviewing the literature.

Controlling methicillin resistant Staphyloccocus aureus and Pseudomonas aeruginosa wound infections with a novel biomaterial.

Wound infections, especially those associated with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, offer considerable challenges for clinicians. Our laboratory has recently developed novel composite biomaterials (DRDC) for wound dressing applications, and demonstrated their in vitro bactericidal efficacy. In the present study, we assessed the proliferation of planktonic and sessile Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus in porcine full-thickness wounds covered for up to 48 h with either saline- or mafenide acetate-loaded DRDC puffs and meshes. All biomaterials were applied 4 h following bacterial inoculation of the wounds with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, to allow colonization of the tissues and initiation of biofilm formation. The drug-loaded biomaterials eradicated both the planktonic and biofilm bacteria in the wounds within 24 h (p <. 05), irrespective of the bacterial strain or architecture of the dressing. While the wound bioburdens increased in the ensuing 24 h, they remained approximately 2 log(10) colony-forming units (CFU) below (p <. 05) their respective baseline values. Similarly, less than 4 log(10) CFU was recovered in the drug-loaded DRDC biomaterials throughout the study. These data show that the DRDC puffs and meshes are effective in delivering certain medications, such as antimicrobial agents, to the wound bed, suggesting considerable value of this material for treating wounds, especially those with irregular shapes, contours, and depths.

Management of bioburden with a burn gel that targets nociceptors.

AIM: To assess the effectiveness of RescuDerm, an amorphous, water-soluble burn gel in controlling Pseudomonas aeruginosa growth in rat full-thickness wounds contaminated with 10(3), 10(5) or 10(7) CFU/g tissue. METHOD: Wounds were treated daily for 72 hours with a placebo gel, a 5% w/w mafenide acetate gel (MAF), or with four modalities of RescuDerm application. RESULTS: All RescuDerm treatments were equally effective within 24 hours in preventing further Pseudomonas aeruginosa growth in wounds contaminated with 10(3) CFU/g tissue. Pseudomonas aeruginosa levels remained at or below this baseline count for 72 hours in all but one of the RescuDerm treatments. The bioburdens in MAF-treated wounds were negligible, averaging 0.14 +/- 0.09 log10 CFU/g tissue. While RescuDerm and MAF remained bacteriostatic in wounds contaminated with 10(5) CFU/g tissue, this property disappeared at higher bioburdens. CONCLUSION: RescuDerm can be used for the management of cutaneous injuries sustained in environments deemed marginally or moderately contaminated. Heavily contaminated wounds would require irrigation prior to application to reduce their bioburden below 10(5) CFU/g tissue.

Seven years' experience with Integra as a reconstructive tool.

The bilayered dermal substitute Integra (Integra Life Sciences Corp., Plainsboro, NJ) was developed and has been widely used as primary coverage for excised acute burns. Our take has been slightly different, finding it most useful in the management of complex soft-tissue loss and threatened extremities as the result of tendon, joint, or bone exposure. Often tasked to fill significant volume loss, we have become adept at stacked multiple-layer applications. Creative use of this material has resulted in unexpected successes with distal limb salvage; the technique takes its place beside adjacent tissue transfer, composite flaps, and vascular pedicle flaps in our burn reconstructive practice. A prospective registry (44 patients) has been kept during the past 7 years that catalogs wounds with complex soft-tissue loss treated with Integra grafts. Many of these patients were at risk of extremity loss because of exposed tendons, joints, or bone. Integra was applied after 1:1 meshing. With profound soft-tissue defects, multiple layers of Integra were serially applied 1 to 2 weeks apart for reconstitution of soft-tissue contours. Local Integra graft infections were managed by silicone unroofing followed by topical sulfamylon liquid dressings. Wounds addressed included fourth-degree burns, necrotizing fasciitis, pit-viper envenomations, and total abdominal wall avulsion in one patient after being run over by a bus. Patients generally were free of pain from their wounds during the maturation phase of the Integra neodermis. Restoration of tissue contour was significantly better when using multiple layers for deep defects. Second and third layers of Integra were successfully applied after an abbreviated first graft maturation period of 7 days. Epithelial autografts on multilayer Integra applications frequently "ghosted"; they would auto-digest to dispersed cells followed subsequently by the reappearance of a confluent epithelial layer. Final grafted skin morphology over palmar and plantar surfaces assumed the type and fingerprint pattern of the original tissues. Infections were readily visible. Early recognition kept them to easily treated circumscribed areas, which did not jeopardize the entire wound. Lengths of stay were long (range, 2-246 days) but not significantly greater than with traditional techniques. The specific reconstructive use of Integra permitted unexpected salvage of several threatened extremities by protecting exposed tendons, bones and joints. Long-term histologic examination revealed unexpected persistence of Integra collagen. Large volume loss wounds benefited from the ability to fill voids with multilayered applications.

Managing extracavitary prosthetic vascular graft infections: a pathway to success.

Prosthetic vascular graft infections portend grave consequences if not treated expediently. Despite the low incidence of infection, the potential for limb loss or death greatly magnifies this complication. The surgical management of prosthetic graft infections has evolved over the last 2 decades. With the myriad therapeutic options now available, an algorithm is necessary to provide the optimal surgical treatment of Samson groups 1 through 5 extracavitary infected vascular prostheses. An extensive review of the literature was undertaken to evaluate the most effective management schemes. The authors found that 3 factors--Samson classification, bacteriology, and patient vascular anatomy--are vital to the surgical strategy. These 3 criteria were examined, and an algorithm was developed based on successful clinical and experimental results. This review provides a step-by-step rationale for the surgical management of extracavitary prosthetic graft infections according to the most successful reported outcomes.

Topical Sulfamylon cream inhibits DNA and protein synthesis in the skin donor site wound.

BACKGROUND: Whereas Sulfamylon is effective in treatment of burn wound infection, controversy exists regarding its effect on the healing process. METHODS: A partial thickness skin donor site wound was created on the back and indwelling catheters were placed in the carotid artery and jugular vein in rabbits under general anesthesia. Sulfamylon cream (8.5%, BERTEK Pharmaceuticals Inc., Morgantown, W Va) was applied on the wound, with either open or occlusive dressing. The control wound was covered with dressings only. On day 7 after injury, stable isotope tracers were infused to determine the fractional synthetic rate (FSR) of DNA, and FSR and fractional breakdown rate (FBR) of protein in the wound. RESULTS: In the Sulfamylon-open dressing group, the DNA FSR was 1.3 +/- 0.6%/day, the protein FSR was 8.0 +/- 3.5%/day, and the net protein deposition (FSR - FBR) was -0.3 +/- 3.7%/day. These values were lower (P < .01 to .05) than the corresponding values in the control group (DNA FSR: 2.9 +/- 0.9%/day; protein FSR: 20.5 +/- 8.4%/day; net protein deposition: 7.9 +/- 6.0%/day). Sulfamylon cream selectively inhibited DNA FSR from the de novo base synthesis pathway (2.3 +/- 1.2 vs 0.8 +/- 0.5%/day, P < .05 vs control). With the occlusive dressing Sulfamylon cream did not decrease wound DNA FSR due to a stimulation of the base salvage pathway, but still decreased protein FSR (11.5 +/- 5.1%/day, P < .05 vs control). Histologic slides indicated that Sulfamylon cream inhibited re-epithelialization, collagen formation, and angiogenesis in the wound. CONCLUSIONS: Topical Sulfamylon cream application inhibited DNA and protein synthesis in the wound, which would be expected to retard the healing process.

Survival benefit conferred by topical antimicrobial preparations in burn patients: a historical perspective.

BACKGROUND: Topical antimicrobial agents have proven efficacy in preventing life-threatening invasive burn wound infection. Under wartime or mass-casualty conditions, however, there may be an inadequate supply of these agents. This study aimed to identify those patients most likely to benefit therefrom. METHODS: Logistical regression analysis of data from the U.S. Army Burn Center was performed. Mortality data for the period immediately preceding the introduction of topical mafenide acetate (MA) (1950-1963) were compared with data for the subsequent period (1964-1968). During the second period, MA was routinely applied but treatment was otherwise similar. The mortality decrement attributed to MA was determined for various ages and burn sizes. RESULTS: For patients of combatant age (20-50 years), MA was associated with a greater than 10% reduction in mortality for those with burns of 40-79% of the total body surface area (TBSA). Only a minimal effect on mortality was noted for those patients with burns smaller than 40% or greater than 79%. CONCLUSIONS: When resources are limited, topical therapy (specifically, MA) is likely to confer the greatest survival benefit for combatants with burns of 40-79% TBSA.