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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

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

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

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

Topical Bactroban (mupirocin): efficacy in treating burn wounds infected with methicillin-resistant staphylococci.

Bacterial antimicrobial susceptibility predictors such as the minimal inhibitory concentration (MIC) assay and Nathans Agar Well Diffusion (NAWD) assay provide essential information relevant to the therapeutic approach in burn-wound sepsis. The susceptibilities of 68 gram-positive burn-wound isolates were tested against topical Bactroban (mupirocin) (Beecham Laboratories, Bristol, Tenn.) and compared with other topical antimicrobials such as mafenide acetate, silver sulfadiazine, and bacitracin/neomycin/polymyxin (BNP). Topical susceptibility data were obtained with a modification of NAWD assay. Bactroban's antimicrobial activity was greater than that of mafenide acetate (100% vs 97%), and significantly greater than that of silver sulfadiazine and that of BNP (p less than 0.001). Of the 68 isolates that were susceptible to Bactroban, 51 were predominately methicillin-resistant staphylococci (MRSA). Bactroban showed in vitro activity against 71% of the 85 gram-negative isolates tested. Mafenide acetate showed activity against 89% of these isolates, a significant difference compared with Bactroban (p less than 0.02). In general, no significant difference was found between the activities of Bactroban and silver sulfadiazine against the gram-negative isolates. The activities of mafenide acetate and silver sulfadiazine against isolates of Pseudomonas aeruginosa were significantly greater than that of Bactroban (p less than 0.05). Bactroban may be used in the treatment of documented staphylococcal burn-wound infections. On the basis of the in vitro data, 13 patients with MRSA burn-wound infections susceptible to Bactroban were evaluated. Quantitative wound biopsies were employed to determine the efficacy of this therapeutic approach. The outcome of these infections was correctly predicted by the NAWD assay in 92.3% of the patients treated (p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical

Effects of topical antimicrobial agents on the human neutrophil respiratory burst.

The neutrophil oxidative burst plays an important role in killing intracellular microorganisms. We studied the effects of topical antimicrobial agents on the N-formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated oxidative burst of human peripheral blood neutrophils, using a flow cytometric assay. Mafenide acetate, sulfadiazine silver, gentamicin sulfate, neomycin sulfate-polymyxin B sulfate (Neosporin GU irrigant), acetic acid, amphotericin B, and povidone-iodine inhibited the neutrophil oxidative burst at or below clinical concentrations, while 0.25% modified diluted sodium hypochlorite (Dakin's) solution caused cell death. Bacitracin-polymyxin B sulfate (Polysporin) greatly augmented the respiratory burst; this effect was due to the bacitracin component. Diluted gentamicin and acetic acid also augmented intracellular hydrogen peroxide production, but to a lesser extent than Polysporin. Inhibition of the respiratory burst of neutrophils might be considered when these agents are used for topical wound care, although clinical correlates of these effects have not been determined.

Acetates

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

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

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

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

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

Suppression of leukocyte chemotaxis in vitro by chemotherapeutic agents used in the management of thermal injuries.

Polymorphonuclear leukocytes from burned patients exhibit suppressed chemotaxis possibly related to the susceptibility of such patients to opportunistic infection. This study assesses the effect of normal serum upon burn-suppressed leukocytes and the effects of three commonly used topical chemotherapeutic agents upon the chemotaxis exhibited by granulocytes from normal controls. In vitro incubation with normal serum restored chemotaxis to normal in the suppressed granulocytes from burned patients. The serum factor responsible for this restoration was heat labile. Serum albumin alone did not exhibit this effect. Both mafenide and silver sulfadiazine suppressed the chemotactic function of granulocytes obtained from normal controls, while silver nitrate exhibited no such activity. Studies of the chemotactic function of control granulocytes after incubation with sera from burned patients yielded similar results; only the sera from patients treated with silver nitrate failed to suppress normal leukotaxis. The chemotactic impairment found in leukocytes from burned patients, however, while related to burn size and predictive of prognosis, did not vary with the agent used for the topical therapy. These data suggest the presence of a reversible intrinsic defect in leukotaxis consequent to burn injury, related to some factor deficient in burn serum. In addition, extrinsic impairment of normal granulocyte leukotaxis by two commonly used chemotherapeutic agents is demonstrated.

Administration, Topical