Topical antimicrobial agents

Burn injury not only produces thermal necrosis of skin, but also causes microvascular thrombosis, leaving the burn avascular and inaccessible to systemic antimicrobials. Topical antimicrobials are designed for direct application to the wound, with the goal of slowing colonization by bacteria and delaying invasive infection. No topical agent is capable of sterilizing the wound. The ideal topical agent should have activity against organisms likely to be encountered on the wound, should not interfere with wound healing, should not be painful or expensive, should have little or no systemic toxicity, and should be easy to apply and remove. Although topical agents may delay the onset of invasive sepsis, they cannot prevent it indefinitely. Surgical wound closure must be obtained as soon as possible.

Topical agents may also play a role in the therapy of invasive wound infections. Therapeutic agents require good penetration of avascular eschar to achieve therapeutic levels at the junction between eschar and viable tissue. Treatment for invasive infection often requires combination therapy with an effective topical agent to control bacterial growth on the wound plus systemic antibiotics to kill organisms invading viable tissue. Surgical debridement is often required to remove infected devitalized burn eschar which may remain on the wound.

Compared with the number and variety of systemic antibiotics available, there are relatively few suitable topical antimicrobials in widespread use.

Silver sulfadiazine, the most widely used topical agent, is bactericidal against a wide range of Gram-positive and Gram-negative enteric organisms. Application is daily and relatively painless, but penetration of the eschar is limited. Although microbial resistance is not common, it does occur and should be considered when colonization persists or the incidence of infection within the intensive care unit (ICU) is excessive.

Silver sulfadiazine has minimal toxicity but is a sulfonamide and should be used with caution in patients who report hypersensitivity to sulfa drugs. Minor skin rashes at the wound margins are common but rarely require a change in therapy. A significant leukopenia occurs in 10 to 15 per cent of patients, usually 2 to 5 days after initiating therapy. Neutrophil counts of less than 1000/mm3 are common but are not associated with an increase in infection and usually disappear within 3 to 5 days.

Mafenide acetate is a sulfonamide derivative with excellent penetration of eschar and has the broadest antimicrobial spectrum of any available topical agent. Unfortunately, mafenide is painful to apply, particularly to partial-thickness areas. Better penetration of eschar is an advantage, but rapid absorption may leave the surface with subtherapeutic levels within hours so that more frequent dressing changes are required. Mafenide reaching the systemic circulation is metabolized to an effective carbonic anhydrase inhibitor. When applied to large surface areas for extended time periods or in the face of renal insufficiency the agent and its metabolite produce metabolic acidosis. Respiratory compensation can drastically increase the work of breathing, leading to respiratory failure. Bacterial resistance is infrequent, but does occur with some methicillin-resistant staphylococci. Mafenide is not usually a first-line agent but is held in reserve for established infection, particularly when needed to penetrate tissue. It is often used in conjunction with silver sulfadiazine; each agent is applied for 12 h in an effort to reduce both toxicity and the development of resistant strains.

Silver nitrate (0.5 per cent) solution in water is bacteriostatic for the organisms found in burn wounds. Bulky layers of dressing material are soaked in silver nitrate solution and applied to the wound, with additional solution applied to keep the wound moist. This constant application will leach electrolytes, particularly chloride, from the circulation. Silver nitrate is messy to use, as it stains everything with which it makes contact. However, the aqueous solution is useful over fresh grafts which will not tolerate the cleaning required to remove the vehicle of cream-based agents.

Although not essential for small burns, topical antimicrobial agents can preserve control of the burn wound for an extended although not indefinite period. They should not be used as a substitute for excision and grafting as soon as donor skin is available.

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