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Mafenide (Sulfamylon) inhibits plasmin fibrinolytic activity.

Inflammatory fibrinolysis by plasmin or phagocyte proteases is a major cause of skin graft failure on burn wounds where the primary adherent attachment of the skin grafts is due to the glue-like action of fibrin. We investigated the potential of mafenide acetate solution, an experimental topical antimicrobial used in treating grafted burn wounds, to modify plasmin fibrinolytic activity in vitro and, thus, its potential to alter or modify the integrity of the fibrin glue critical for skin graft viability. Immobilized 125I-fibrin monolayers were used to assay fibrinolytic activity from plasmin or from plasma activated by streptokinase or urokinase and modified by the presence of mafenide or epsilon-aminocaproic acid (EACA). While streptokinase-activated plasma lysed 52.7 +/- 3.9% of the 125I-fibrin, this plasmin activity was more than 80% inhibitable by EACA. Mafenide acetate had no intrinsic fibrinolytic activity (1.5 +/- 0.3%) nor activated plasma fibrinolytic potential (2.4 +/- 0.5%), but produced significant and dose-related reduction in fibrinolytic activity (p less than 0.001). Other sulfonamide analogues lacking a para-methylamino reactive group had 10-100 fold less antifibrinolytic potency while lysine, like mafenide, able to compete for plasmin binding sites, could potently block fibrinolysis. Mafenide did not qualitatively alter activation of plasminogen or affect generation of complexes with alpha 2 antiplasmin complexes. Adding mafenide only minutes following streptokinase-activated plasma or plasmin with the fibrin substrate reduced antifibrinolytic activity, supporting the conclusion that mafenide, like EACA, can modulate the interaction between fibrin and the plasmin reactive sites and thus prevent close plasmin/fibrin apposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Fibrinolysin

Studies of the pain produced by mafenide acetate preparations in burns.

In a double-blind triple cross-over clinical study, 37 patients were exposed to several formulations of mafenide acetate (Sulfamylon Cream) and their pain responses were recorded and converted to a semiquantitative pain index. The 11.2% concentration in cream was two to three times more painful than the 5% concentration. Hypertonicity and not the pH level appears to be the cause of the pain produced by the high (11.2%) concentration. The tonicity of the cream carrier and 11.2% mafenide acetate are 1,080 mOsm/kg and 1,100 mOsm/kg, respectively, for a total of 2,180 mOsm/kg. The carrier cream without glycerol and a 5% concentration of mafenide cream were much less painful than the 11.2% concentration of mafenide. Both afforded a great deal of relief to the patients who received the medications.

Administration, Topical

The effect of mafenide on dihydropteroate synthase.

Using intact bacterial cells, it was found that Pseudomonas aeruginosa was more susceptible to mafenide than Escherichia coli, that p-aminobenzoic acid (pABA) did not reverse or prevent inhibition by mafenide and that pABA itself was inhibitory. Under the experimental conditions used in these studies, pABA was more inhibitory to E. coli than to P. aeruginosa. It is proposed that pABA could be of use in the topical treatment of burn wounds. At the enzyme level, it was shown that mafenide did not inhibit dihydropteroate synthase. Thus, mafenide appeared not to exert its inhibitory effects in the same manner as the structurally related sulphonamides.

4-Aminobenzoic Acid

Differential inhibition of human basal keratinocyte growth to silver sulfadiazine and mafenide acetate.

The impact of topical antimicrobial agents on improving the survival of patients with major thermal injuries is significant. However, the effects of these agents on cells responsible for wound healing has only recently received attention. Fresh human basal keratinocytes were grown in serum-free modified MCDB 153 medium under standard tissue culture conditions. Cells were subsequently exposed to concentrations of silver sulfadiazine and mafenide acetate as low as 1/100 of that used clinically over a period of 5-7 days. Cellular responses documented with hemocytometer cells counts, cellular protein assays, phase-contrast microscopy, and transmission electron microscopy show only severe toxicity to mafenide acetate. Such data imply that inhibition of wound epithelialization is greater with the use of mafenide acetate than with the use of silver sulfadiazine.

Cell Count

Mafenide-induced pseudochondritis.

Wound infections following burns of the ear can result in the devastating complication of chondritis, requiring resection of cartilage. To prevent this, it has become common practice to dress the burned ear with mafenide acetate. We have observed six hypersensitivity reactions to the mafenide that occurred following several weeks of continuous use of the drug. The reaction mimics chondritis, causing edematous, erythematous, pruritic ears with a profuse serous exudate. There is no associated fever, systemic signs, or pain on motion of the cartilage. Treatment consists of stopping the mafenide. Recovery occurs within 72 hours. Differentiating between chondritis, with its required surgical and antibiotic treatment, and a hypersensitivity reaction is necessary to avoid further iatrogenic injury.

Adult

Inhibition of Pseudomonas burn wound infection by mafenide dry foam.

The results of an in vivo evaluation of 8.5% mafenide dry foam are described. Using burned guinea pigs infected with Pseudomonas aeruginosa, mafenide was applied every 12 hr as the dry foam or as the commercially available ointment. After 156 hr of therapy with the medicated dosage forms, the previously infected areas did not demonstrate the presence of Pseudomonas. However, all nonmedicated, infected controls produced positive cultures. Both medicated dosage forms demonstrated equivalent efficacy in the inhibition of Pseudomonas on burn wounds.

Administration, Topical

Wet disc testing of mafenide hydrochloride, chlorhexidine gluconate, and triple antibiotic solution against bacteria isolated from burn wounds.

Various antimicrobial solutions for topical use on burn wounds tested, in vitro with a newly described wet disc assay, for their activity against bacterial isolates from patients with burns. The antimicrobial activity of triple antibiotic solution was shown to reside in the neomycin component. The activity of 2.5% mafenide hydrochloride solution was equal to that of 4% mafenide HCl and could be used clinically with significant savings and perhaps, fewer side effects. Chlorhexidine gluconate had broad antimicrobial activity in an 0.05% solution in water; however, dissolving the active ingredient in saline nullified its activity significantly. The wet disc assay appears to be a useful means by which to assess the efficacy of solutions for topical use.

Bacitracin

Comparison of silver sulphadiazine 1 per cent, silver sulphadiazine 1 per cent plus chlorhexidine digluconate 0.2 per cent and mafenide acetate 8.5 per cent for topical antibacterial effect in infected full skin thickness rat burn wounds.

Silver sulphadiazine 1 per cent (SS), silver sulphadiazine 1 per cent plus chlorhexidine digluconate 0.2 per cent (SS + CD 0.2 per cent) and mafenide acetate 8.5 per cent (MA) were compared to assess the antibacterial effect of once daily application on experimental rat 20 per cent full skin thickness burn wounds seeded 24 h earlier with 10(8) microorganisms originally isolated from infected wounds of burned patients. Separate series evaluated Staph. aureus, Enterococcus faecalis, Enterobacter cloacae and Ps. aeruginosa. The mean concentration of all four organisms recovered after 1 week from full thickness biopsies of eschar and from separate biopsies of subjacent muscle was less in MA and SS + CD 0.2 per cent treated animals compared with those treated with SS alone. The mean concentration in muscle and eschar following treatment with MA was less for wounds seeded with Staph. aureus and Ps. aeruginosa than with SS + CD 0.2 per cent treatment, while the mean concentration in eschar application of SS + CD 0.2 per cent was less than with MA for E. faecalis seeded wounds.

Administration, Topical

Use of 5% sulfamylon (mafenide) solution after excision and grafting of burns.

In previous reports, 5% sulfamylon solution has been utilized on unexcised burns and granulation tissue. We prospectively evaluated 67 burn patients to determine graft take and the incidence of side effects with use of sulfamylon solution dressings after excision and grafting. Of patients excised and grafted, the mean graft take for a total of 100 procedures was 86%. Rash occurred in 18% of patients and sulfamylon was discontinued with no sequelae. Twenty-five percent had at least one positive fungal wound culture, yet only 3% required treatment for candidemia. Those patients who developed a rash and fungal colonization had a significantly larger percent burn and were treated with sulfamylon for a longer period of time. Pain intensity was rated on a Visual Analog Scale with a mean score of 2.4; in no case was the pain considered severe enough by the patient to terminate treatment. Acidosis was present in 3% of patients but felt to be unrelated to the sulfamylon treatment. As an antimicrobial agent, 5% sulfamylon solution is a viable alternative for fresh autografts with excellent graft take and acceptable side effects.

Administration, Topical

Mafenide acetate solution dressings: an adjunct in burn wound care.

A continuation of the study of 5% aqueous Sulfamylon solution dressings in burned patients was analyzed in 150 consecutive cases. The rate of invasive infection and mortality was not excessive. Dressings were used as an adjunct to other topical chemotherapeutic agents as well as homo/heterograft skin in the overall burn care program. Sulfamylon soaks were shown to be effective for debridement, granulation tissue protection and preparation, and bacterial control. The dressings were comfortable when in place and the wounds appeared clean. Epithelialization was not hampered so that the dressings could be utilized in partial thickness wounds as well as for mesh autografts on extensive burn surfaces=

Adolescent