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PubMed1999

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.

Antifungal Agents↗
PubMed1976

In vitro penetration of topical antiseptics through eschar of burn patients.

The ability of topical antiseptics to penetrate eschar of burn patients was determined by the agar diffusion technique. Gentamicin sulfate, mafenide acetate, nitrofurazone, povidone-iodine, silver nitrate, and silver sulfadiazine were tested against clinical isolates of Candida albicans, Staphylococcus, Streptococcus, and gram-negative bacilli including Pseudomonas aeruginosa. In practically all instances, the diameters of the zones of inhibition observed using eschar were comparable to those obtained with filter-paper discs. This finding showed that the antimicrobial agents could penetrate eschar and retain their effectiveness after penetration.

Anti-Infective Agents, Local↗
PubMedDate not supplied

Preventing postoperative burn wound aspergillosis.

Between January 1, 1984, and December 31, 1988, 35 patients at the Los Angeles County + University of Southern California Burn Center had postoperative cultures from their burn wounds that grew Aspergillus species; clinical burn-wound aspergillosis occurred in 66% of these cases and death occurred in 53% of these cases. Beginning in November 1984, several modifications in the air-conditioning system and topical antimicrobial wound therapy were undertaken. Cleaning and 8Cu-quinolinolate treatment of air ducts every 2 months did not reliably clear Aspergillus species from the air in patient care areas. Several changes in topical therapeutic regimen failed to prevent both burn wound culture positivity and clinical aspergillosis. Finally, installation of high-efficiency particulate air filters, installation of new air ducts, and inception of wound irrigation with a solution of mafenide hydrochloride plus nystatin both during and after operation were associated with a reduction in wound culture positivity rate to one occurrence in 1988 (Poisson probability less than 0.01 versus the rate in 1984) and no occurrences during the 18 months after the false ceiling of the burn ward was sealed.

Aspergillosis↗
PubMedDate not supplied

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.

Animals↗
PubMed1978

Resistant Enterobacter cloacae in a burn center: the ineffectiveness of silver sulfadiazine.

Enterobacter cloacae sepsis was found in 15 burn center patients in 1976, of whom 13 died. Nine of the deaths occurred in the first 60 days. The Burn Center isolates were resistant to silver sulfadiazine (AgSD) in agar cup-plate tests and confirmed by tube dilution tests. Hospital, non-burn isolates of E. cloacae were sensitive to AgSD. All E. cloacae isolates were sensitive to mafenide acetate (MA) in the agar cup-plate tests, but this was not confirmed by the tube dilution tests. The agar cup-plate susceptibility test is a simple, rapid and effective technique for determining resistant and sensitive isolates of E. cloacae. Patients who were changed from AgSD to MA because of resistant E. cloacae infection did not have improved survival. An animal study showed that AgSD was ineffective against this strain of E. cloacae and that MA was more effective than AgSD when applied 24 hr postburn but neither were effective at 48 hr postburn. MA was bacteriostatic but not bactericidal with this E. cloacae strain.

Animals↗
PubMed1988

The antifibrinolytic activity of sulfamylon solution.

Sulfamylon (mafenide) solution, a potent experimental topical antimicrobial, is used in our burn unit to treat burn wounds both before and after skin grafting. The importance of fibrin to early graft adherence prompted this in vitro study of the effect of Sulfamylon upon fibrin clot. Assessing fibrinolysis by in vitro proteolysis of [125I] fibrin monomers, Sulfamylon, at relevant clinical concentrations, produced dose-related inhibition of streptokinase-mediated fibrinolysis. In addition, Sulfamylon had no intrinsic fibrinolytic activity. This antifibrinolytic property of Sulfamylon solution may, in vivo, protect against early graft loss when used on burn wounds and other potentially contaminated graft sites.

Antifibrinolytic Agents↗
PubMed2001

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.

Administration, Topical↗
PubMed2004

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.

Administration, Topical↗
PubMed1976

Protein metabolism in burned rats.

Incorporation of [2-14C]glycine was used to estimate serum protein synthesis in four groups of rats. These were the control (group C); 20% body surface burn (group B); 20% burn, seeded with Pseudomonas aeruginosa (group BI); and burned-infected treated topically with mafenide (alpha-amino-p-toluenesulfonamide) acetate (group BIS), a treatment which controls P, aeruginosa burn-wound infection in humans. On the 6th day postburn the relative specific activities of all fractions were increased in the order BI greater than BIS greater than B greater than C, as were the concentrations of the globulins; Serum albumin concentration fell, being lowest in BI. Tissue albumin contents, measured by radioimmunoassay, of eviscerated blood-free bodies of rats were (mg/100 g rat wt): C, 207; B, 294; BI, 256. Analyses of individual tissues showed that the difference was due to increased albumin content in the burn-wound area. The tissue albumin was of normal molecular size and was immunologically reactive. We conclude that the prolonged hypoalbuminemia following burn injury is not a consequence of impaired albumin synthesis, but a result of altered compartmentation.

Animals↗
PubMed1978

Treatment of necrotizing fasciitis caused by Staphylococcus epidermidis.

Postoperative necrotizing fasciitis with septicemia caused by Staphylococcus epidermidis was documented by cultures of the blood and wound biopsy specimen. Therapy consisted of surgical debridement, topical application of mafenide acetate dressings, and parenteral administration of cefazolin sodium. The combination effectively reversed the progression of infection and necrosis.

Abdominal Muscles↗
PubMed1994

Cytoprotection of human dermal fibroblasts against silver sulfadiazine using recombinant growth factors.

Topical antimicrobial agents, silver sulfadiazine (SSD) and mafenide acetate (MA), have been associated with delayed wound healing. Previous in vitro studies with human dermal fibroblasts (HDF) have shown progressive cellular cytotoxicity with increasing concentrations of SSD and MA. However, preexposure of HDF to epidermal growth factor, basic fibroblast growth factor, or platelet-derived growth factor has resulted in cytoprotection of HDF against 0.01 and 0.03% concentrations of SSD as determined by phase-contrast microscopy (PCM), hemocytometer cell counts, and total cellular protein content. PCM, however, showed slower destruction of HDF at the 0.05% concentration of SSD. These data suggest that cells activated by growth factors either take up less SSD or are more resistant to the direct cytotoxic effects of this drug.

Epidermal Growth Factor↗
PubMed1988

A comparison of Biobrane vs. homograft for coverage of contaminated burn wounds.

An evaluation was made comparing homograft to Biobrane for the coverage of excised burn wounds using a rat model which had been contaminated with 1 x 10(5) Pseudomonas aeruginosa 1244. The homograft and Biobrane were then covered with either silver sulphadiazine cream, a 5 per cent mafenide acetate solution, or no topical antibacterial agent. Five days later the wounds were examined to determine the percentage of graft take. The homograft was found to have a superior graft take in this model. It is therefore recommended that a surgeon using Biobrane for the first time ensures the wound is at least as free of bacterial contamination as he would if he were using homograft.

Animals↗
PubMed1989

Analysis of infection in a burn ward.

One hundred and seventy-two burn wound swabs obtained from 90 patients admitted to the Aljila Hospital Burn Unit, Benghazi over a 3-month period were processed to determine the microbial flora colonizing burns and their resistance patterns to selected locally available topical and systemic agents. Approximately 84.9 per cent of the swab specimens yielded growth of 11 bacterial species and Candida spp.; of these, Ps. aeruginosa, Staph. aureus and Klebsiella spp. predominated in order of prevalence, followed by Enterobacteria. Polymyxin (100 per cent sensitive), amicacin (90.9 per cent sensitive) and carbenicillin (66.7 per cent sensitive) were the most effective of 10 selected antibiotics tested against the 60 pseudomonas isolates. In studies in vitro using six topical agents, Ps. aeruginosa strains were most sensitive, in decreasing order, to mafenide acetate, silver sulphadiazine, acetic acid, silver nitrate and Eusol. Seventy-eight per cent of Staph. aureus isolates were resistant to methicillin and erythromycin and 93 per cent to tetracycline.

Anti-Bacterial Agents↗
PubMed1989

Susceptibility of Pseudomonas and Staphylococcus wound isolates to topical antimicrobial agents: a 10-year review and clinical evaluation.

A 10-year review of Ps. aeruginosa and Staph. aureus susceptibility to various topical agents is presented. Susceptibility testing was performed using the agar well diffusion (AWD) method. A reduction in microbial growth to numbers less than 10(5) per gram of tissue in the wound, measured by quantitative biopsy, was compared with predicted susceptibility test results. In this measurement of clinical efficacy, silver sulphadiazine and mafenide acetate compared most favourably with AWD results, 83 per cent and 82 per cent respectively. However, nitrofurazone only reduced bacterial counts to less than 10(5) per gram 42 per cent of the time when an inhibition zone was present. Hydrogen peroxide solution (1 per cent) was 100 per cent effective by the AWD test, but no relationship to clinical efficacy could be shown. Minimal inhibitory concentration (MIC) data for gentamicin sulphate was compared to AWD and showed a positive relationship of greater than 80 per cent for both organisms. The AWD test has been a useful aid in the decision-making process for the choice of topical agent by providing data which eliminates agents inappropriate for use.

Administration, Topical↗
PubMed1996

Treatment of a severe alkali burn.

The case history of a 20-year-old male patient who sustained an 85 per cent total body surface area alkali burn to his skin, after falling into a caustic lime pit, is reported. Considerable problems regarding the correct estimate of burn wound depth, predominant location of the deepest burn on the posterior half of the body, appropriate wound coverage, and lack of sufficient skin graft donor sites required a complex treatment plan. Excisions to fascia and intradermal debridement were required to achieve an appropriate bed for wound closure. Five per cent mafenide acetate solution (Sulfamylon) was applied to prevent burn wound sepsis. Human allografts and Biobrane were used extensively to achieve temporary wound closure, to provide mechanical protection of freshly autografted wounds, and to prevent desiccation following application of cultured epidermal autografts on to debrided wounds and split thickness skin grafted donor sites. The case illustrates a number of problems associated with the evaluation and treatment of patients suffering severe alkali burns, and demonstrates the implementation of both established and evolving technologies in the management of these injuries.

Adult↗
PubMed1996

Hyperbaric oxygen therapy and piracetam decrease the early extension of deep partial-thickness burns.

During the first 24 h, a progression of the burn wound in histological depth or extension is often noted. This can only partially be prevented by the routinely used protocols of fluid resuscitation and burn wound dressing. In a rat model of 5% TBSA burn, hyperbaric oxygen therapy (HBOT) and piracetam were evaluated for their ability to further prevent this early deepening of the burn wound. After infliction of the burn wound, the animals were treated with an accepted basic burn wound treatment consisting of mafenide 10% solution humid dressings. They were then randomized into three groups: a control group (n = 10), receiving no other treatment, a HBOT group (n = 17), receiving 60 min of HBOT (203 kPa) twice daily, and a piracetam group (n = 19), receiving piracetam (200 mg/kg IM) twice daily. On the third day of treatment, the entire burn wound was exised and examined histologically. It was found that both HBOT and piracetam had statistically significant effects on the preservation of epidermal basal membrane (P < 0.001 and P < 0.01, respectively). HBOT, but not piracetam, further had significant effects on the destruction of skin appendages (P < or = 0.05 and P > 0.05, respectively) and on the degree of subepidermal inflammation, as measured by leucocyte infiltration (P < 0.001 and P > 0.05, respectively). Furthermore, the HBOT group showed significantly less leucocyte infiltration than the piracetam group (P < 0.01). It was concluded that, although the clinical importance of the small effects on skin appendage and basal membrane preservation may be questionable, the effect on subepidermal leucocyte infiltration is striking and warrants further investigation of the anti-inflammatory effects of HBOT and possibly piracetam.

Animals↗
PubMed2005

Burn care standards in Israel: lack of consensus.

UNLABELLED: In recent years, the need for a national burn center based on ABA guidelines has emerged in Israel. The formation of such a center is now underway in the Chaim Sheba Medical Center. As a first step in the standardization of burn care in Israel, we have conducted a nation-wide survey among burn care personnel (physicians, nurses and other burn team members), regarding different aspects of the treatment of burn patients. METHODS: A questionnaire comprised of 30 questions regarding the severity of burns admitted, the site of initial management, wound care (both burn/skin-graft sites and donor sites), dressing changes protocols, sterility precautions, hydrotherapy, and pressure dressings was presented to 70 health-care professionals involved in the treatment of burns. RESULTS AND DISCUSSION: Seventy-seven percent of interviewed personnel participated in the survey. Consensus was found regarding most local (topical) wound care, (SSD for clean non-facial burns, Sulfamylon (mafenide-acetate) for contaminated non-facial burns, Threolone (chloramphenicol 3% and prednisolone 0.5%) or Bacitracin for facial burns, Paraffin gauzes with or without Sulfamylon for donor and graft sites). Dressing changes regimes were also agreed upon generally. However, there was no consensus regarding the ideal time for the removal of donor site dressings and this issue will need to be resolved. Other important findings are that both Edinborough University Solution of Lime (EUSOL), which has been deemed unsuitable for burn treatment due to toxic effects, and hydrotherapy, which has been proposed as a source of infection and contamination, are still widely used. We anticipate that these issues will be settled in our unified national burn care protocols (which are currently under development and revision).

Administration, Topical↗
PubMed2000

A historical review of the use of silver in the treatment of burns. II. Renewed interest for silver.

In 1965, Moyer revived interest in silver nitrate solution. He concluded on the basis on in vitro and in vivo studies that a 0.5% solution represented the lowest concentration at which antibacterial action (against Staphylococcus aureus, haemolytic streptococci and generally against Pseudomonas aeruginosa and E. coli) was obtained. Mafenide acetate was introduced a short time after the reintroduction of silver nitrate, followed a few years later by silver sulphadiazine. Thus, in a short period of time three medicaments appeared on the market which represented a radical change in the topical treatment of burns. The action of silver sulphadiazine has been intensively studied. Since silver sulphadiazine does not offer sufficient protection to prevent or retard the growth of gram-negative bacteria in patients with burns covering more than 50% of body surface, Monafo introduced the combined preparation silver sulphadiazine and cerium nitrate. Although various attempts have been made to develop more effective silver compounds, so far silver sulphadiazine still remains the most widely used substance of this type.

Anti-Infective Agents, Local↗