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.

Mafenide derivatives inhibit neuroinflammation in Alzheimer's disease by regulating pyroptosis.

The main mechanism of pyroptosis is Caspase-1-mediated GSDMD cleavage, and GSDMD is also the executive protein of pyroptosis. Our previous study has shown that mafenide can inhibit pyroptosis by inhibiting the GSDMD-Asp275 site to suppress cleavage. In this study, sulfonamide was used as the parent nucleus structure to synthesize sulfa-4 and sulfa-20. Screening of drug activity in the pyroptosis model of BV2 and iBMDM cell lines revealed the efficacy of five compounds were superior to mafenide, which exerted a better inhibitory effect on the occurrence of pyroptosis. For in vivo assay, Sulfa-4 and Sulfa-22 were intervened in the neuroinflammation APP/PS1 mice. As a result, the administration of Sulfa-4 and Sulfa-22 could significantly inhibit the activation of microglia, decrease the expression of inflammatory factors in the central nervous system and simultaneously suppress the production of p30-GSDMD as well as the expression of upstream NLRP3 inflammasome and Caspase-1 protein. Immunoprecipitation and Biotin-labelled assay confirmed the targeted binding relationship of Sulfa-4 and Sulfa-22 with GSDMD protein in the iBMDM model in vitro. In this study, we investigated a new type inhibitor of GSDMD cleavage, which exerted a good inhibitory effect on pyroptosis and provided new references for the development of inflammatory drugs in the future.

Investigation on the mechanism of mafenide in inhibiting pyroptosis and the release of inflammatory factors.

OBJECTIVE: The present study was designed to investigate the roles and mechanism of mafenide (MAF) in targeted inhibition of Gasdermin D (GSDMD) cleavage and in suppressing pyroptosis. METHODS: Lipopolysaccharide (LPS) and Nigericin were used to induce pyroptosis in mouse bone marrow-derived macrophages (iBMDM) and mouse microglia (BV2). Lactate dehydrogenase (LDH) release rate and Propidium Iodide (PI) uptake rate were used to detect cytotoxicity, Western blot was used to detect the protein expression, and Enzyme-linked immunosorbent assay (ELISA) was utilized to detect the expression of inflammatory factors from culture medium. MAF was labeled with biotin and subsequently subjected to Pull-down assay to detect its binding to GSDMD. GSDMD-Asp275 site was further mutated to validate the binding of MAF to GSDMD. Finally, the effects of MAF on inflammatory factor release and microglial activation were confirmed in the APP/PS12 animal model. RESULTS: MAF could inhibit pyroptosis in iBMDM and microglia BV2, and decrease the release of inflammatory factors. MAF could inhibit GSDMD cleavage by directly binding to the GSDMD-Asp275 site, while the expression of p30-GSDMD was simultaneously down-regulated and the release of inflammatory factors was decreased. MAF could reduce the levels of inflammatory factors in cerebrospinal fluid and peripheral blood of APP/PS1 mice, and suppress the activation of microglia. CONCLUSION: The mechanism underlying the regulation of MAF on inflammatory response was correlated with the inhibition of pyroptosis. MAF could inhibit GSDMD cleavage by directly binding to GSDMD.

Pharmacological screening of a new alpha-2 adrenergic receptor agonist, mafedine, in zebrafish.

Pharmacological agents acting at alpha-2 adrenergic receptors are widely used in physiology and neuroscience research. Mounting evidence of their potential utility in clinical and experimental psychopharmacology, necessitates new models and novel model organisms for their screening. Here, we characterize behavioral effects of mafedine (6-oxo-1-phenyl-2- (phenylamino)-1,6-dihydropyrimidine-4-sodium olate), a novel drug with alpha-2 adrenergic receptor agonistic effects, in adult zebrafish (Danio rerio) in the novel tank test of anxiety and activity. Following an acute 20-min exposure, mafedine at 60 mg/L produced a mild psychostimulant action with some anxiogenic-like effects. Repeated acute 20-min/day administration of mafedine for 7 consecutive days at 1, 5 and 10 mg/L had a similar action on fish behavior as an acute exposure to 60 mg/L. Since mafedine demonstrated robust behavioral effects in zebrafish - a sensitive vertebrate aquatic model, it is likely that it may modulate rodent and human behavior as well. Thus, further studies are needed to explore this possibility in detail, and whether it may foster clinical application of mafedine and related alpha-2 adrenergic agents.

The Effective Duration of Antimicrobial Activity of Mafenide Acetate After Reconstitution.

Mafenide acetate is an effective but costly antimicrobial solution used for burn wounds. The package insert instructs the user to discard unused solution within 48 hours of opening. The purpose of this study is to evaluate the antimicrobial activity of mafenide acetate beyond 48 hours after reconstitution, to possibly reduce cost by eliminating product waste. Staphylococcus aureus and Pseudomonas aeruginosa isolates were used to seed Mueller-Hinton agar plates. Filter paper disks were then saturated with 5% mafenide acetate at 0, 2, 7, 14, 30, and 60 days after reconstitution. Disks were then placed on the seeded agar plates and incubated. After incubation, the zone of inhibition around each plate was measured. A zone of inhibition of 2 mm or greater was indicative of susceptibility. Mafenide acetate remained efficacious, with a zone of inhibition of >2 mm to both organisms at 0, 2, 7, 14, 30, and 60 days after mafenide acetate reconstitution. This in vitro study demonstrates that the antimicrobial activity of mafenide acetate remains present for at least 60 days after reconstitution. Unused mafenide may not need to be discarded at 48 hours after opening. Reducing wasted product has the potential to translate into cost savings.

Thermal stability of mafenide and amphotericin B topical solution.

OBJECTIVE: Fungal infections remain a major cause of mortality in the burned population. Mafenide acetate/amphotericin B solution (SMAT) has been used topically for prophylaxis and treatment of these infections. Current manufacturer guidelines only guarantee the stability of mafenide solution and amphotericin B at room temperature. Additionally, the recommended maximum storage time for mafenide solution is 48h, leading to significant financial and material loss when unused solutions are discarded. The purpose of this study was to characterize the chemical stability, structure and bioactivity of SMAT stored at 2°C, 25°C, and 40°C for up to 90 days. METHODS: Stability analyses of SMAT solutions containing 2.5% or 5% mafenide plus 2µg/mL amphotericin B were performed using high performance liquid chromatography. Chemical structure was assessed using Fourier-transform infrared spectroscopy. Bioactivity against clinically relevant species was examined. RESULTS: The chemical structure and stability of mafenide did not change over 90days at all temperatures. Amphotericin B was undetectable in SMAT solutions after two days at high temperatures, which was slowed by refrigerated storage. Against Staphylococcus aureus, SMAT activity began to decrease generally between two and seven days. Against Pseudomonas aeruginosa, activity slowly tapered and was gone by day 90. SMAT retained high bioactivity against Candida albicans for over 40days and was not affected by temperature. CONCLUSIONS: The amphotericin B component of SMAT is degraded within 2days under warm storage. While mafenide was stable over 90 days, the bioactivity of SMAT solution may be lost within 2days as well.

[Effects of topical agents for burns on Acinetobacter baumannii within biofilm].

OBJECTIVE: To observe the antimicrobial activity of topical agents commonly used for burns on Acinetobacter baumannii (AB) in both free and biofilm states, and their synergistic effect with ambroxol on AB within biofilm. METHODS: Eleven AB strains were isolated from wound excretion, respiratory tract, and blood of patients hospitalized in our hospital from August 2005 to April 2007. (1) The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of mafenide acetate and chlorhexidine acetate to free AB (including drug-resistant, drug-sensitive, and standard strains) were determined by dilution method. (2) AB was cultured with LB or TSB medium for 12, 24, and 48 h to form biofilm, and it was treated with above-mentioned two topical agents in MBC (mafenide group and chlorhexidine group) for 30 min. Biofilm not treated by topical agent was used as control group. The biofilm thickness was determined with confocal laser scanning microscope. The proportion of living bacteria in biofilm was calculated. AB biofilm in each topical agent group was mixed and inoculated into LB culture dish to observe the growth of bacteria. (3) AB was cultured with LB medium for 48 h to form biofilm, which was respectively treated by above-mentioned two topical agents in MBC (mafenide group and chlorhexidine group) and combination of each topical agent with 3.75 mg/mL ambroxol solution (ambroxol + mafenide group and ambroxol + chlorhexidine group) for 30 min. Biofilm not treated by topical agents was used as control group. Growth of bacteria in biofilm was detected with MTT method (denoted as absorbance value). Data were processed with one-way analysis of variance and LSD-t test. RESULTS: (1) MIC of mafenide acetate and chlorhexidine acetate for free AB was respectively 25.00 mg/mL and 0.03 mg/mL. MBC of both agents for free AB was the same as their MIC. (2) Among three groups, the thickness of biofilm of sensitive AB was thicker than that of drug-resistant bacteria at most of the time points. Compared with those in control group, biofilm thickness and proportion of living bacteria in biofilm were slightly decreased in mafenide and chlorhexidine groups. The growth of bacteria was abundant in each group. (3) Absorbance value of drug-resistant bacteria in control, mafenide, and chlorhexidine groups was respectively 0.776 ± 0.071, 0.625 ± 0.063, and 0.420 ± 0.068. Absorbance value of drug-resistant bacteria in ambroxol + mafenide group (0.174 ± 0.089) was significantly lower than that of control group (t = 11.823, P = 0.000) and mafenide group (t = 9.248, P < 0.01). Absorbance value of ambroxol + chlorhexidine group (0.178 ± 0.044) was significantly lower than that of control group (t = 16.009, P = 0.000) and chlorhexidine group (t = 6.681, P < 0.01). CONCLUSIONS: Drug-resistant AB forms biofilm readily, which prevents topical agents from killing the bacteria inside. Combined use of ambroxol with topical agents gives synergistic effect on killing AB in biofilm in the wound.

Comparison between topical honey and mafenide acetate in treatment of auricular burn.

The auricle is a frequently injured part of the head and neck during thermal injury leading to ear deformity. The burned ear represents one of the most difficult problems for reconstructive surgeons. Mafenide acetate is a topical agent used routinely for these patients, but it has some disadvantages including painful application and allergic rash. Some authors have reported the healing effect and antibacterial activity of honey. The study reported here was undertaken to compare the effect of honey and mafenide acetate on auricular burn in rabbit. In our study, although the pathologic score of the honey group was better than that of the mafenide group both on 14 and 21 days after burning, it was not statistically significant. In the mafenide acetate group, deep complication of burn (chondritis) was significantly lower than that of the honey group. In conclusion, in contrast to healing and antibiotic activity reported for honey, it may have failure in preventing deep bacterial complications of wound (like chondritis). So in deep wounds, the use of honey as dressing is not recommended.

Highly antibiotic-resistant Acinetobacter baumannii clinical isolates are killed by the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG).

Acinetobacter baumannii is an increasingly common cause of infection in intensive-care units throughout the world, and the occurrence of multiresistant A. baumannii is increasing. The aim of this study was to determine whether a highly purified polyphenol, (-)-epigallocatechin-3-gallate (EGCG), from green tea (Camellia sinesis), had antimicrobial effects against multiresistant clinical isolates of A. baumannii. Standard microplate assays were performed to determine the MIC of EGCG for 21 clinical isolates of A. baumannii. MICs ranged from 0.078 to 0.625 mg/mL, with MIC(50) and MIC(90) of 0.312 mg/mL and 0.625 mg/mL, respectively. All of the isolates of A. baumannii tested were killed by EGCG. In time-kill assays, EGCG resulted in a 3-log reduction in CFU/mL of A. baumannii after 5 h of incubation with the polyphenol. Synergy between the commonly used topical agent 5% mafenide acetate (Sulfamylon) and EGCG was noted for one clinical isolate, and partial synergy was noted for three other isolates. These findings demonstrate that EGCG is an effective bactericidal agent against antibiotic-resistant A. baumannii clinical strains in laboratory settings. EGCG has previously been shown to be safe, and therefore may be an attractive addition for the treatment of cutaneous A. baumannii infections where high concentrations of the drug can be applied to the wound surface.

Effects of commonly used topical antimicrobial agents on Acinetobacter baumannii: an in vitro study.

Acinetobacter baumannii has recently emerged as an important pathogen among wounded soldiers in Iraq. Because of its ability to develop resistance to antimicrobial agents, wound infections with A. baumannii are difficult to treat and can lead to septicemia and even death. Use of appropriate topical antimicrobial agents in these circumstances could be one of the first steps in the prevention of A. baumannii wound infections. In this study, we present the in vitro effects of seven common topical antimicrobial creams and dressings on A. baumannii. A. baumannii was subjected to sensitivity tests with mupirocin, silver sulfadiazine, mafenide acetate, a double-antibiotic combination of polymyxin and bacitracin, a triple-antibiotic combination of neomycin, bacitracin, and polymyxin, and two silver-containing dressings. Zones of inhibition were measured after 24 hours of incubation. Of the evaluated antimicrobial agents, mafenide acetate was the most efficacious, followed by mupirocin and triple- and double-antibiotic combinations (in decreasing order). The silver-containing dressings yielded smaller zones of inhibition, compared to the previously mentioned agents, and no zone of inhibition was observed with silver sulfadiazine. Further in vivo studies on the effects of antimicrobial agents against A. baumannii are necessary to substantiate these findings and to determine the potential clinical relevance of these therapies.

Comparative evaluation of silver-containing antimicrobial dressings and drugs.

Wound dressings containing silver as antimicrobial agents are available in various forms and formulations; however, little is understood concerning their comparative efficacy as antimicrobial agents. Eight commercially available silver-containing dressings, Acticoat 7, Acticoat Moisture Control, Acticoat Absorbent, Silvercel, Aquacel Ag, Contreet F, Urgotol SSD and Actisorb, were tested to determine their comparative antimicrobial effectiveness in vitro and compared against three commercially available topical antimicrobial creams, a non treatment control, and a topical silver-containing antimicrobial gel, Silvasorb. Zone of inhibition and quantitative testing was performed by standard methods using Escherichia coli, Pseudomonas aeruginosa, Streptococcus faecalis and Staphylococcus aureus. Results showed all silver dressings and topical antimicrobials displayed antimicrobial activity. Silver-containing dressings with the highest concentrations of silver exhibited the strongest bacterial inhibitive properties. Concreet F and the Acticoat dressings tended to have greater antimicrobial activity than did the others. Topical antimicrobial creams, including silver sulfadiazine, Sulfamylon and gentamicin sulfate, and the topical antimicrobial gel Silvasorb exhibited superior bacterial inhibition and bactericidal properties, essentially eliminating all bacterial growth at 24 hours. Silver-containing dressings are likely to provide a barrier to and treatment for infection; however, their bactericidal and bacteriostatic properties are inferior to commonly used topical antimicrobial agents.

Methylamine but not mafenide mimics insulin-like activity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism.

It has been reported that benzylamine reduces blood glucose in rabbits, stimulates hexose uptake, and inhibits lipolysis in mouse, rabbit, and human adipocytes. In the presence of vanadate, benzylamine is also able to improve glucose disposal in normoglycaemic and diabetic rats. Such insulin-mimicking properties are the consequence of hydrogen peroxide production during benzylamine oxidation by semicarbazide-sensitive amine oxidase (SSAO). The aim of the study was to determine whether other SSAO-substrates could share such potential antidiabetic properties. Thus, mafenide, a synthetic antimicrobial sulfonamide structurally related to benzylamine, and which has been recently reported to interact with SSAO, was tested in the above mentioned models, in parallel with methylamine, a proposed endogenous SSAO-substrate. All tested amines stimulated glucose uptake and inhibited lipolysis in rat and mouse fat cells. Methylamine and benzylamine, but not mafenide, reduced the hyperglycaemic response during a glucose tolerance test in rabbits while the three amines tested were devoid of insulin-releasing activity under both in vivo and in vitro conditions. In human adipocytes, mafenide did not stimulate glucose transport since it was not a high-affinity substrate for SSAO and generated less hydrogen peroxide than benzylamine or methylamine. Therefore, mafenide could not be considered as an antidiabetic drug despite being oxidized and exhibiting insulin-mimicking effects in rat and mouse adipocytes. By contrast, the endogenous substrate methylamine improved glucose utilization in all in vitro and in vivo models, leading to consider novel SSAO substrates as drugs with potential anti-hyperglycaemic properties.

An in vivo comparison of topical agents on wound repair.

Selection of the ideal antiseptic or antimicrobial treatment for contaminated wounds remains a controversial decision. Clinical decisions are often made on the basis of in vitro studies and personal preference. Although topical solutions are widely used, their comparative in vivo effects on wound healing are largely unreported.A porcine wound model was used to compare five commonly used topical agents-5% mafenide acetate (Sulfamylon solution), 10% povidone with 1% free iodine (Betadine), 0.25% sodium hypochlorite ("half-strength" Dakin), 3% hydrogen peroxide, and 0.25% acetic acid-with a control group. Reepithelialization, angiogenesis, neodermal regeneration, fibroblast proliferation, collagen production, and bacterial colony counts were analyzed at 4 and 7 days after wounding (n = 4). Reepithelialization was not significantly influenced among the various treatment modalities tested. Sulfamylon and Dakin solutions significantly increased neodermal thickness (p < 0.05), whereas hydrogen peroxide and acetic acid significantly inhibited neodermal formation (p < 0.001). All treatments except hydrogen peroxide significantly increased fibroblast proliferation. Sulfamylon and Betadine significantly enhanced angiogenesis (p < 0.05). Sulfamylon proved most effective in maintaining an aseptic environment while concomitantly increasing angiogenesis, fibroblast proliferation, and dermal thickness compared with control. These data show that selection of a particular topical treatment can affect various aspects of wound repair in an animal model. These results suggest that the selection of topical treatments in the clinical setting should be carefully tailored to match unique wound situations and therapeutic endpoints.

Off-label drug use in WOC nursing: issues related to use of mafenide acetate to treat infected chronic wounds.

It is not unusual for practitioners to prescribe off-label drugs for their patients--that is, drugs that have not yet been approved by the Food and Drug Administration to treat the patient's particular condition. The decision to use off-label drugs should be based on a clear understanding of the risks and benefits to the patient. This issue is pertinent to WOC nurses because they may work with physicians who prescribe off-label drugs for their wound care patients. In addition, WOC nurses who are also nurse practitioners and have prescribing privileges may be intimately involved in the decision to prescribe off-label drugs. A review of the literature related to off-label drug use and mafenide acetate was conducted. This article presents the issues related to off-label use of mafenide acetate (Sulfamylon) and possible implications for patients with chronic infected wounds.

Efficacy of topical silver against fungal burn wound pathogens.

BACKGROUND: Fungal infections of burn wounds have become an important cause of burn-associated morbidity and mortality. The nature of fungal infections dictates aggressive treatment to minimize the morbidity associated with these infections. Persons with large total body surface area burns are particularly susceptible to fungal infections and are treated in such a manner as to minimize their risk of infection. METHODS: This study examined the in vitro fungicidal efficacy of a variety of different topical agents. By placing fungal inocula in contact with mafenide acetate, silver nitrate, silver sulfadiazine, and a nanocrystalline silver-coated dressing, we determined the kill kinetics of these topical agents against a spectrum of common burn wound fungal pathogens. RESULTS: The topical antimicrobials that were tested demonstrated varying degrees of efficacy against these pathogens. CONCLUSION: The nanocrystalline silver-based dressing provided the fastest and broadest-spectrum fungicidal activity and may make it a good candidate for use to minimize the potential of fungal infection, thereby reducing complications that delay wound healing.

Comparative evaluation of the antimicrobial activity of ACTICOAT antimicrobial barrier dressing.

This study evaluated the antimicrobial activity of ACTICOAT Antimicrobial Barrier Dressing (Westaim Biomedical Corp, Fort Saskatchewan, Alberta, Canada), a silver-coated wound dressing, and compared it with silver nitrate, silver sulfadiazine, and mafenide acetate. The minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC), zone of inhibition, and killing curves were determined with 5 clinically relevant bacteria. The data indicate that ACTICOAT silver had the lowest MIC and MBC and generated similar zones of inhibition to silver nitrate and silver sulfadiazine. Viable bacteria were undetectable 30 minutes after inoculation with the dressing, whereas it took 2 to 4 hours for silver nitrate and silver sulfadazine to achieve the same result. Mafenide acetate generated the biggest zones of inhibition, but it had the highest MICs and MBCs, and a significant number of bacteria still survived after 6 hours of treatment. The results suggest that ACTICOAT Antimicrobial Barrier Dressing has better antimicrobial performance than either of the existing silver-based products. ACTICOAT dressing killed the bacteria that were tested much faster, which is a very important characteristic for a wound dressing acting as a barrier to invasive infection to have. The study also suggests that a single susceptibility test such as a MIC or zone of inhibition test does not provide a comprehensive profile of antimicrobial activity of a topical antimicrobial agent or dressing. A combination of tests is desirable.

The efficacy of 5% Sulfamylon solution for the treatment of contaminated explanted human meshed skin grafts.

Large TBSA burns have a deficiency of skin graft donor sites necessitating meshed skin autografts, cultured epithelial autografts or biosynthetic skin substitutes. Because these do not effect immediate complete biological closure of the wound, the burn victim remains at risk for life-threatening infection. Topical antimicrobials can protect colonization of these grafts from becoming invasive sepsis. However, many of these agents are cytotoxic to new partially keratinized epithelial cells. This study using a model of epithelialization kinetics of human meshed skin grafts explanted to athymic 'nude' rats evaluated: (1) the effect of bacterial colonization on the rate of closure of meshed graft interstices; (2) the efficacy of 5% Sulfamylon solution for bacterial control and (3) the effect on interstitial closure rates caused by control of bacterial proliferation. Results showed the rate of interstitial closure was progressive over 7 days in noncontaminated grafts treated with moistened saline dressings. Areas of total closure of a 1:1.5 meshed graft were seen as early as 5 days. When grafts were inoculated with 10(2) or 10(3) Pseudomonas aeruginosa organisms and treated with saline moistened dressings, the resultant bacterial load rose to 10(6) organisms, less than 3% of the interstices closed and grafts were destroyed. With the same organism level of contamination, bacterial levels were eradicated with topical 5% Sulfamylon solution, interstitial closure rates returned to normal and areas of total meshed graft closure were seen by day 4. These data demonstrate the efficacy of 5% Sulfamylon solution on epithelialization kinetics of contaminated meshed skin grafts.

Topical sulfamylon reduces engraftment of cultured skin substitutes on athymic mice.

Sulfamylon (mafenide acetate) remains extremely valuable for the control of the bacterial contamination of burn wounds, but it is cytotoxic to cultured keratinocytes used for wound closure. Because composite skin substitutes develop a partial epidermal barrier in vitro, they may hypothetically tolerate the use of topical Sulfamylon. To test this hypothesis, cultured skin substitutes were prepared from cultured human fibroblasts; keratinocytes were attached to these collagen-based substrates, which were grafted to full-thickness wounds in athymic mice (n = 8 per group). Wounds were irrigated twice daily with 5% (wt/vol) Sulfamylon solution or with a formulation of noncytotoxic antimicrobials (0% Sulfamylon). On day 9 after grafting, the wounds were treated with dry dressings and assessed at 4 weeks for expression of human leukocyte antigens-A, B, C and at 2, 3, and 4 weeks for percentage of original wound area and surface electrical capacitance in picofarads (pF). Data were analyzed for statistical significance (P < .05) by Fisher's exact test, Student's t test, and repeated measures analysis of variance: [table: see text] The data demonstrate that irrigation of cultured skin substitutes with a solution of 5% Sulfamylon results in smaller wound area, fewer wounds that contain human cells, and greater surface hydration (higher surface electrical capacitance) than irrigation with noncytotoxic antimicrobial agents. These results support the conclusion that cultured skin substitutes of this type do not tolerate the chemical toxicity of Sulfamylon as well as skin autografts. Further improvements in the properties of the epidermal barrier of cultured skin substitutes may facilitate the use of Sulfamylon or other potent antimicrobial agents for the management of microbial contamination during engraftment of transplanted skin cells.

Comparison of the effects of commonly used wound agents on epithelialization and neovascularization.

BACKGROUND: The primary effect sought with most topical wound therapy is antimicrobial. Topical wound agents are thought to promote normal healing by protecting the wound from infection. In this study, we examined the effect of six commonly used topical wound agents (bacitracin, sodium hypochlorite, silver nitrate, silver sulfadiazine, mafenide acetate, and povidone-iodine) on epithelialization and neovascularization in noninfected wounds. For this study, a new wound model was used in which direct visualization and quantification of wound epithelialization and neovascularization were carried out throughout the entire healing process. STUDY DESIGN: We measured the effect which 500 U per g of bacitracin, 0.25 percent of sodium hypochlorite, 0.5 percent silver nitrate, 1 percent silver sulfadiazine, 8.5 percent mafenide acetate, and 10 percent povodione-iodine had on the rate of wound epithelialization and neovascularization. The agents were applied topically to 99 circular full-thickness wounds (2.25 mm diameter, 0.125 mm depth) created on the dorsum of male hairless mouse ears. This model enabled us to visualize and measure directly wound epithelialization and neovascularization repeatedly throughout healing, using intravital video microscopy and computerized digitized planimetry. RESULTS: Control wounds and wounds treated with silver sulfadiazine (n = 18) and mafenide acetate (n = 14) epithelialized in 7.2 +/- 0.7, 7.1 +/- 0.3, and 7.3 +/- 0.3 days, respectively. This was significantly (p < 0.01) faster than the wounds treated with povidone-iodine (n = 10), sodium hypochlorite, (n = 8), and bacitracin (n = 13). Wounds treated with povidone-iodine epithelialized the slowest (11.8 +/- 0.55 days). Wound neovascularization was completed most rapidly in the groups treated with povidone-iodine and silver sulfadiazine (15.0 +/- 0.4 and 15.3 +/- 0.7 days, respectively). This was significantly (p < 0.05) faster than wounds treated with silver nitrate (n = 15), which neovascularized in 18.4 +/- 0.56 days. One-half of the wounds treated with sodium hypochlorite (eight of 16) did not epithelialize or neovascularize. CONCLUSIONS: The various antimicrobial agents studied in our in vivo model affect wound epithelialization and neovascularization differently. These effects on these two very important aspects of healing should be taken into consideration when indicating a specific agent for treatment of different types of wounds.