Systemic absorption of amphotericin B with topical 5% mafenide acetate/amphotericin B solution for grafted burn wounds: is it clinically relevant?

OBJECTIVE: To determine if patients receiving topical amphotericin B in combination with 5% mafenide acetate solution will acquire systemically detectable levels of amphotericin B. METHODS: A prospective, observational study of consecutive patients from May 2007 to March 2008 who received 5% mafenide acetate/amphotericin B (2 mcg/ml) solution topically every 4h to their excised and grafted burn wounds for at least 5 days. Serum amphotericin B levels were measured every 5 days during treatment. In addition, the percentage of graft take, occurrence of infection, and potential adverse reactions or toxicities were monitored and recorded. RESULTS: A total of 27 patients were enrolled, accumulating 420 treatment days and 72 amphotericin B levels. Sixty-nine of the amphotericin B levels were undetectable, while 3 were detectable at non-therapeutic levels (<0.5 mcg/ml). Of the patients with a detectable serum amphotericin B level, only one experienced adverse reactions that could potentially be attributed to amphotericin B. The mean TBSA burned was 32% (SD+/-14%), with a mean TBSA treated with solution of 21% (SD+/-13%). The median duration of treatment was 8 days (range 5-52 days), and the median number of amphotericin B levels drawn per patient was 1 (range 1-19). The median percentage graft take was 95%, and there were no fungal wound infections. CONCLUSIONS: We conclude that 5% mafenide acetate/amphotericin B (2 mcg/ml) solution, applied to excised and grafted burn wounds, does not produce clinically relevant serum levels of amphotericin B. Based on our observations, this topical regimen is safe.

Comparison of therapeutic antibiotic treatments on tissue-engineered human skin substitutes.

For regenerative medicine to gain clinical acceptance, the effects of commonly used treatment regimens on bioengineered organs must be considered. The antibiotics mafenide acetate (mafenide) and neomycin plus polymyxin (neo/poly) are routinely used to irrigate postoperative skin grafts on contaminated wounds. The effects of these clinically used antibiotics were investigated using tissue-engineered human skin substitutes generated with primary human keratinocytes or the near-diploid human keratinocyte cell line, Near-diploid Immortal Keratinocytes. Following topical or dermal treatment, the skin substitutes were assayed for viability, tissue morphology, glycogen content, and the expression of active caspase 3. Mafenide, but not neo/poly, induced morphological and biochemical changes in tissue-engineered skin substitutes. Keratinocytes in all histological layers of mafenide-treated skin substitutes exhibited ballooning degeneration and glycogen depletion. Mafenide-treatment also triggered separation of basal keratinocytes from the underlying dermis. None of the antibiotic treatments induced apoptosis, as measured by active caspase 3 immunostaining. The results demonstrate that mafenide, but not neo/poly, is detrimental to the viability and structural integrity of tissue-engineered human skin substitutes. These findings highlight the need to identify treatment regimens that are compatible with and hence enable the therapeutic efficacy of first-generation bioengineered organs such as skin.

Allergic contact dermatitis to mafenide acetate: a case series and review of the literature.

Burn patients with extensive involvement of body surface area (BSA >30%) represent a challenge in wound treatment. Multiple topical agents may be used for cleansing, barrier protection, and antimicrobial control leading to complications of contact and/or irritant dermatitis, which may further complicate re-epithelization and eventual wound healing. We present 4 patients who sustained extensive burns during Operation Iraqi Freedom/Operation Enduring Freedom and later developed contact dermatitis to mafenide acetate, a common topical antimicrobial used in burn care treatment, also known as Sulfamylon (alpha-amino-p-toluenesulfonamide monoacetate). All patients who were patch tested to mafenide acetate 7% solution were positive. A rechallenge with mafenide acetate resulted in recrudescence of the eruption in 2 out of the 4 patients. Though cutaneous reactions to mafenide acetate were reported by Yaffe and Dressler in 1969, the most recent case reports are from 1995. This paper presents more recent examples of cutaneous reactions to mafenide acetate, while also reviewing the literature.

Mafenide acetate allergy presenting as recurrent chondritis.

Acute chondritis has a strong predilection for recurrence. Mafenide acetate has been implicated in causing reactions that mimic this condition; however, these hypersensitivity reactions lack fever, fluctuance, and pain. The authors report a case of mafenide acetate allergy presenting as recurrent chondritis in a patient who had previously been treated successfully for this condition. In this patient, the allergic response resolved within 3 days after cessation of mafenide acetate. If unappreciated, it may have led to unnecessary operative intervention. Therefore, auricular edema and erythema, without fever, fluctuance, and pain, must be recognized by surgeons as a possible mafenide acetate allergy and must be considered in the differential diagnosis for patients who present with recurrent acute suppurative chondritis.

Serious silver sulphadiazine and mafenide acetate dermatitis.

Infrequently reported, serious allergic reactions to topical antimicrobial agents used in the treatment of burn injuries are a potential source of confusion. To avoid misdirected therapy, an understanding of the manifestations of such reactions is important. Two recent cases of serious allergic reactions, one to silver sulphadiazine, one to mafenide acetate, are presented and the literature is reviewed.

Five percent mafenide acetate solution in the treatment of thermal injuries.

A 5% mafenide acetate solution was used in the treatment of 669 patients with thermal injuries. This solution was used as the initial topical antibacterial agent in the treatment of the acute burn wound in 276 patients. It was initiated during the intermediate and chronic phases of burn wound therapy in 393 patients. Acid-base derangements did not occur. Discontinuation of therapy because of the patient's pain was necessary in fewer than 1% (17 of 669) of all patients treated. The incidence of rash and pruritus was extremely low. Effective antibacterial activity was achieved. This solution appears to be an effective, safe, and versatile antibacterial agent that produces minimal side effects and is useful in all phases of burn wound management.

[Algimaf treatment of trophic ulcers]. / Lechenie troficheskikh iazv al'gimafom.

A new biologically active preparation, algimaf, developed at the All-Union Research Institute for Medical Polymers, stimulates the regenerative processes, is characterized by analgesic, antiedematous, manifest antibacterial and hemostatic effects, promotes the formation of hardly visible cicatrices, and is a highly effective means for the management of trophic ulcers of the skin.

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.

Sulfamylon allergy simulating chondritis.

A case of atopic reaction to Sulfamylon is described that occurred in a patient receiving this medication as a topical treatment for burned ears. The presenting signs were similar to those of a persistent chondritis, with which it was initially confused. All signs and symptoms cleared rapidly after the Sulfamylon was discontinued. Physicians should be aware of this entity so as to avoid inappropriate surgical debridement of ears with this relatively minor problem.

Methaemoglobinaemia induced by mafenide acetate in children. A report of two cases.

The local application of mafenide acetate (Sulfamylon, Winthrop) applied to extensive burn areas resulted in acute methaemoglobinaemia.

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.

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=

Progressive pulmonary insufficiency and other pulmonary complications of thermal injury.

Progressive pulmonary insufficiency appears to be a universal response to the lung to a variety of injuries which damage the pulmonary-capillary emdothelium. Persistent hyperventilation, unresponsive to the administration of oxygen, is the earliest clinical sign of this complication of trauma and should prompt close monitoring of pulmonary function (measurement of arterial blood gas and pH levels, Vd/Vt A-aDo2, minute ventilation, vital capacity and inspiratory force) to assess the severity of the disease, the need for mechanical ventilatory support and the effectiveness of treatment. Other pulmonary complications of burn injury range from carbon monoxide poisoning and narcotics overdosage in the immediate postburn period through marked hyperventilation directly related to burn size occurring in the absence of significant parenchymal change to later occurring hematogenous and airborne pneumonia. Inhalation injury, a chemical tracheobronchitis which significantly increases the mortality of a given-sized burn, may be present immediately postburn but clinically inapparent for 48-72 hours. 133Xenon lung scans permit early diagnosis of this pulmonary injury and the timely institution of a graduated therapeutic response keyed to the severity of pulmonary disability. Knowledge of the pathogenesis of each of these complications is requisite for the physician caring for burn patients and permits the employment of rational preventive and therapeutic measures.