Mafenide Research Articles

ALTERNATIVE FORMS OF LOCAL TREATMENT FOR BURNS

In a controlled trial of three alternative methods for local treatment of severe burns, a significantly lower incidence of bacterial colonisation was recorded in burns treated with local chemoprophylactic agents than in those treated by exposure in warm, dry air. Of the local chemoprophylactic methods, compresses of 0.5% silver-nitrate solution gave better protection in general against bacterial colonisation than 11.2% mafenide ('Sulfamylon') acetate cream with exposure of burns, but infection with Pseudomonas œruginosa occurred about as often in burns treated with silver-nitrate compresses as in those treated with mafenide cream. Miscellaneous coliform bacilli colonised similar proportions of burns in the three treatment groups. The mean of the highest respiration-rates per patient was significantly higher in patients treated by exposure in warm, dry air than in those treated with silver-nitrate compresses. The mean respiration-rate of patients treated with mafenide was slightly higher than that of patients in the silver-nitrate group, and slightly lower than that of patients in the group treated by exposure in warm, dry air; the mean temperature of patients treated with mafenide was slightly lower than that of the patients treated by exposure, but not apparently different from that of patients treated with silver-nitrate compresses. Mortality in each group was slightly, but not significantly, lower than that expected on a probability chart based on findings in the unit during the years 1965-70. Most of the patients treated with mafenide did not complete the course of treatment because of pain; acidosis occurred only in one patient treated with this agent. Side-effects of silver-nitrate treatment were noted in some patients, including low serum-sodium, acidosis, and diarrhœa. A trial of 1% silver-sulphadiazine cream on smaller burns showed that daily reapplication of the cream gave significantly better protection than reapplication every three or four days; the prophylactic effects of this treatment were similar, whether burns were covered with dressings or exposed.

Current problems in burns. A perspective.

A comparison of fluid and electrolyte formulas in common usage reveals that the quantities of sodium and water recommended for burned children by the Evans, Brooke, and Shriner's Burn Institute (Boston) formulas, though calculated differently, are essentially the same. In large burns (80%), the Baxter formula gives twice as much sodium as the Evans or Brooke. In moderate burns (40%), the difference is considerably less. The use of colloid is necessary in severely burned children and in adults diminishes the need for lactated Ringer's solution. Mafenide acetate (Sulfamylon Cream), silver nitrate, and gentamicin reduce burn wound bacteria significantly and effect significant control over burn wound infection. Skin homografts and xenografts have made a major contribution to burn therapy. A new standard for fabric flammability for children's nightwear is proposed which could save hundreds of lives.

The behavior of mafenide acetate as a basis for its clinical use.

Mafenide acetate has been studied using human and animal tissue. It behaves similarly in burned tissue of both species, rapidly penetrating the burn wound. Eighty to ninety percent of the dosage enters the wound within five hours and attains a peak concentration at one to two hours, two to five times that required for minimal bacterial inhibition. The drug declines in concentration in the wound to subinhibitory levels in eight to ten hours, requiring reapplication at that time for maximum effectiveness. Six to eight percent of the drug is bound by plasma protein. Its excretion is principally by the kidney, with halftimes in all organs and plasma of 10 to 15 minutes, and total excretion within six days. The drug strongly inhibits protein synthesis in Pseudomonas aeruginosa.

The burn wound and its care.

Thermal injury of the skin results in striking anatomic, metabolic, and physiologic disturbances which prejudice survival of burn patients. Identification of burn wound sepsis and description of its pathogenesis led to the development of effective topical burn wound chemotherapy. Mafenide acetate (Sulfamylon Cream), now employed in more than 2,000 burn patients, is applied to control bacterial proliferation within the burn wound prior to eschar separation. Other topically applied agents may be used for this purpose. Cutaneous allografts and heterografts serve as temporary physiologic dressings after eschar separation, providing continuing bacterial control until autografting. Control of burn wound bacterial proliferation has been associated with the emergence of other opportunistic burn wound infections, ie, fungal and viral, necessitating frequent biopsy monitoring of the burn wound. A significant improvement in survival of burn patients thus managed is documented. In burns involving large areas of skin, the patient is exposed to death first, from shock; second, from toxemia due to absorption of poisons from the injured surfaces; third, from loss of function of the absent skin covering; and fourth, from exhaustion due to the longcontinued fight for recovery. Haldor Sneve, 19051

Mafenide acetate in burn treatment.

Elsewhere in this issue White and Asch present a detailed series of observations on the renal and pulmonary effects of carbonic anhydrase inhibition secondary to absorbed mafenide acetate (Sulfamylon) and its conversion product, paracarboxybenzine sulfonamide. Their data demonstrate that peak blood levels of the two agents occurred within two or three hours of application and were associated with increased renal excretion of bicarbonate, falling arterial bicarbonate levels compensated by hyperventilation resulting in a decreased arterial Pco2, and maintenance of normal blood pH. Similarly, inhibition of red-cell carbonic anhydrase resulted in a delay in carbon dioxide transfer across the . . .

Acid-base effects of topical mafenide acetate in the burned patient.

Abstract Ten burned patients were observed for 24 hours after treatment with topical mafenide acetate cream. This drug was rapidly absorbed systemically and converted to p-carboxybenzenesulfonamide. Both agents are carbonic anhydrase inhibitors. The highest blood levels of mafenide and p-carboxybenzenesulfonamide occurred during the second to the fourth hour in patients with decreased renal function and extensive areas of partial-thickness burn. The urine became persistently alkaline in nine of the 10 patients, suggesting renal carbonic anhydrase inhibition. Six of the patients with the highest drug blood levels had a transient increase in the arterialalveolar carbon dioxide tension gradient during the first to the 12th hours of mafenide therapy, suggesting inhibition of red-cell carbonic anhydrase. At 24 hours, both drug levels and the difference between arterial and alveolar carbon dioxide tension had returned to pretreatment values. Despite renal and red-cell carbonic anhydrase inhibition, no consisten...

Mafenide acetate (sulfamylon) and silver sulphadiazine creams for local treatment of burns

Infection, especially with Pseudomonas aeruginosa and some other Gram-negative bacilli, is a major cause of death in severely burned patients. In attempts to combat such infection classical asepsis and systemic chemotherapy have been less successful than local chemoprophylaxis. Creams containing polymyxin, neomycin and some other antibiotics help, but compresses of 0.5% silver nitrate solution,1 2 and gentamicin cream3 4 appear to be better. Unfortunately silver nitrate gives little or no protection against Klebsiella and some other Gram-negative bacilli and is relatively ineffective against established infection: prophylactic use of gentamicin is likely in the long run to select out resistant strains of Ps. aeruginosa, and is therefore better reserved for the treatment of systemic pseudomonas sepsis. Two newer agents for local antimicrobial prophylaxis and treatment are mafenide acetate cream5 and silver sulphadiazine cream which is not yet marketed.6

Fungal Burn Wound Infection

Recent emergence of mycotic burn wound infection as a clinicopathological entity suggested a possible relationship to the use of topical antibacterial therapy. The autopsy incidence of fungal burn wound infection was determined for periods prior to and after the institution of mafenide acetate (Sulfamylon cream) therapy (topically administered) in 1964. There has been a tenfold increase in wound infections due to Phycomycetes and Aspergillus species, since 1964. These two organisms are also the fungi most frequently responsible for clinical mycotic burn wound infection.

Effects of silver nitrate and sulfamylon on epithelial regeneration.

Effects of silver nitrate and sulfamylon on epithelial regeneration.

Topical application of mafenide acetate. Its association with erythema multiforme and cutaneous reactions.

Four hundred burn patients, ambulatory and hospitalized, were treated with mafenide acetate in a hydrophilic cream base. The incidence of cutaneous reaction was 9.5%, most of which were localized and minor. This did not interfere with the control of sepsis and at the time of occurrence, only one patient required further topical therapy. Two patients developed erythema multiforme which presented a diagnostic and therapeutic problem. This incidence of reaction is acceptable in the hospitalized patients with a severe burn.

Topical Application of Mafenide Acetate

Four hundred burn patients, ambulatory and hospitalized, were treated with mafenide acetate in a hydrophilic cream base. The incidence of cutaneous reaction was 9.5%, most of which were localized and minor. This did not interfere with the control of sepsis and at the time of occurrence, only one patient required further topical therapy. Two patients developed erythema multiforme which presented a diagnostic and therapeutic problem. This incidence of reaction is acceptable in the hospitalized patients with a severe burn.

TLC and Sulfamylon for Burned Children

TLC and Sulfamylon for Burned Children

TLC and Sulfamylon for Burned Children

TLC and Sulfamylon for Burned Children

Hyperglycemic, nonketotic coma in the patient with burns: Factors in pathogenesis

Hyperglycemic, nonketotic coma developed in an individual with a family background of diabetes mellitus who suffered severe second and third degree burns. Treating the patient with a formula high in carbohydrate content and covering the burned area with mafenide acetate, an ointment known to enhance the insensible water loss in burned patients, apparently precipitated the hyperosmolar state. Coma developed when the plasma glucose was 900 mg. per 100 ml., the plasma immunoreactive insulin 10 μU per ml. and free fatty acid level 655 μEq. per liter. A hereditary tendency for diabetes, high carbohydrate diets, dehydration and beta cell failure all have a role in the pathogenesis of hyperglycemic, nonketotic coma in the patient with burns.

Combined systemic and topical therapy of experimental burn wound sepsis.

TOPICAL mafenide (Sulfamylon) acetate B in a hydrophilic base has recently been shown to effectively reduce the mortality from burn wound sepsis both in the laboratory and clinically. This therapy has been based largely on the work of Teplitz 1 and Lindberg 2 and subsequently substantiated in our laboratory showing that the mortality is directly related to the degree of burn wound sepsis as measured by eschar and subeschar bacterial counts and that the bacterial invasion of a burn wound occurs at a predictable rate. Topical mafenide has been shown by Lindberg 3 to be progressively less effective if the initial application is delayed until 48 hours postburn or longer. Systemic antibiotics have not significantly reduced burn mortality probably due to their inability to achieve effective concentrations in the burn with its damaged vascularity, 4,5 and still remain within safe systemic levels of the antibiotic. Sodium colistimethate (Coly-Mycin Injectable) has

Preliminary observations on the toxicity of the hydrochloride and acetate salts of mafenide (sulfamylon R )

Mafenide acetate was found to produce less metabolic acidosis and to be significantly less toxic than mafenide hydrochloride following intravenous administration in experimental animals. It would appear, therefore, that the acetate salt of mafenide offers an improvement over mafenide hydrochloride in burn wound treatment.