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POST-BURN INFECTION & SEPSIS Before embarking on the antimicrobial therapeutic approach in the treatment of burn wound sepsis, it is important to establish certain consistencies in terminology.
Infection is the most common and most serious complication of a major burn injury related to burn size. Sepsis accounts for 50-60% of deaths in burn patients today despite improvements in antimicrobial therapies. Sepsis in burns is commonly due to bronchopneumonia, pyelonephritis, thrombophlebitis, or invasive wound infection. The burn wound is an ideal substrate for bacterial growth and provides a wide portal for microbial invasion. Microbial colonization of the open burn wounds, primarily from an endogenous source, is usually established by the end of the first week. Infection is promoted by loss of the epithelial barrier, by malnutrition induced by the hypermetabolic response to burn injury, and by a generalized post-burn immunosuppression due to release of immunoreactive agents from the burn wound. Burn injury leads to suppression of nearly all aspects of immune response. Post-burn serum levels of immunoglobulins, fibronectin, and complement levels are reduced, as well as a diminished ability for opsonization. Chemotaxis, phagocytosis, and killing function of neutrophils, monocytes, and macrophages are impaired. Granulocytopenia is common following burn injury. Cellular immune response is impaired, as evidenced by delayed allograft rejection, anergy to common antigens, impaired lymphocyte mitogenesis, and altered mixed lymphocyte responsiveness. Burn injury results in reductions of interleukin-2 (Il-2) production, T-cell and NK cell cytotoxicity, and helper to suppressor T-cell ration (HSR). Furthermore, infusion of serum from burned to normal patients or animals can transmit some of these immunosuppressive effects. Control of Infection The goals of local wound management are the prevention of dessication of viable tissue and the control of bacteria. These are achieved by use of topical antimicrobial agents and/or biological dressings. It is unrealistic to expect to keep a burn wound sterile. Bacterial counts of less than 103 organisms/gm are not usually invasive and allow skin graft survival rates of >90%. Antimicrobial therapy is
directed by bacterial surveillance through routine tri-weekly sputum, urine,
and wound cultures. In addition, punch biopsies for each 18% BSA of
burn are obtained qMWF for wound monitoring until the wound is closed.
Quantitative wound biopsy is a better determinant of significant pathogens
than qualitative surface swabs. Organism identification and Diagnosis of sepsis in burn
patients can be difficult to distinguish from the usual hyperdynamic,
hyperthermic, hypermetabolic post-burn state. Blood cultures are
commonly negative. Fever spikes are not proportional to degree of
infection. 1) burn wound infection (>105
organisms/gm tissue) with histologic or clinical evidence of invasion Local evidence of invasive wound infection includes: › black or brown patches of wound
discoloration Appropriate systemic antibiotics are administered as indicated. The appropriate use of antibiotics should be based on the following definitions:
Topical Antimicrobials Silver sulfadiazine (e.g. Silvadene or SSD) is the most commonly used topical antimicrobial agent in burns. Its antimicrobial properties are derived from the dual mechanisms of its silver and sulfa moieties (functional parts), and has a broad spectrum of antimicrobial coverage including gram positive bacteria, most gram negative bacteria, and some yeast forms. Some gram negative organisms (e.g. some Pseudomonas species), do possess a plasmid mediated resistance. Unlike mafenide or silver nitrate, silver sulfadiazine does not hinder epithelialization, although it does hamper contraction of fibroblasts. Furthermore, silver sulfadiazine is painless on application, has high patient acceptance, and is easy to use with or without dressing. Although true allergic sensitivities are rare, many patients will develop a transient leukopenia 3 to 5 days following its continued use secondary to margination of circulating white blood cells. This leukopenia is generally harmless and merits observation, but not cessation of treatment. However, if the white blood cell count drops below 3000, the medication is sometimes withheld until the WBC count returns to >4000-5000. Mafenide acetate 11.2% cream (e.g. Sulfamylon) is one of the oldest effective topical antimicrobial agents. Mafenide has a broad spectrum of antimicrobial activity, including silver sulfadiazine-resistant Pseudomonas and enterococci, but reduced antifungal properties. Its exact mechanism of action is not clear, but thought to be related to its water-soluble sulfa moiety. Mafenide cream is toxic to epithelial cells and fibroblasts. Unlike other topical agents, mafenide has good penetration through the eschar. For this reason mafenide is commonly used on dirty or infected burn wounds, or electrical burns, and on burned ears to prevent chondritis. Following its application, mafenide produces a manful sensation for several minutes, thereby earning its nickname of 'white lightning'. Mafenide can cause an allergic skin rash. Through carbonic anhydrase inhibition, mafenide can also cause bicarbonate wasting in the kidneys, hyperchloremia, systemic metabolic acidosis and compensatory hyperventilation. To protect against such metabolic abnormalities one can sequentially follow serum electrolyte levels and treat abnormal values with appropriate intravenous replacement therapy. Alternatively, applications of mafenide cream can be limited to no more than 20% of the BSA at any one time. The sites of mafenide applications can then be rotated every 2 hours until the entire burn has been treated. We will often alternate mafenide and silver sulfadiazine creams on seriously contaminated wounds as a form of 'pulse therapy'. Silver nitrate 0.5% solution is a broad spectrum, non-penetrating, painless antimicrobial agent. It requires multiple daily applications on burn dressings and is messy and staining. The solution is hypotonic; so electrolyte leeching, hyponatremia, and hypokalemia are common side-effects. A rare complication of silver nitrate use is methemoglobinemia. Silver nitrate dressings are used in treatment of toxic epidermal necrolysis syndrome and in rare patients allergic to silver sulfadiazine or mafenide. Petroleum-based antimicrobial ointments such as bacitracin and/or polymyxin B are clear on application, painless, and allow for easy wound observation. These agents are commonly used for treatment of facial burns, graft sites, healing donor sites, and small partial-thickness burns. Povidone iodine ointment has a broad antimicrobial activity, including bacteria, fungi, and some viral forms. Mupirocin (e.g. Bactroban) has improved activity against gram positive bacteria, especially methillin resistant Staph. aureus (MRSA) and selected enteric bacteria. Gentamicin ointment will select for resistant organisms and diminish effectiveness of its parenteral form, but may be useful in selected cases. In severely burned patients (>40% BSA), the combination of Mycostatin ointment or powder with other topical agents reduces the incidence of fungal superinfection and improves antimicrobial action. Mycostatin should not be combined with mafenide, however, because both become inactivated. In addition, Mycostatin 5-15 ml given orally 3 times daily reduces alimentary fungal overgrowth. This regimen has markedly decreased the incidence of candida septicemia in our patients. Topical antimicrobial creams are usually used with closed dressings. This provides for greater patient comfort and less dessication than the open technique. The creams are spread on fine mesh gauze, applied on the wounds, then covered with bulky protective gauze dressing and an elastic compressive wrap. Dressing changes are performed every 8 to 12 hours. At each dressing change, wounds are gently cleaned prior to re-application. In contaminated or suspicious areas, the wounds are washed with an antimicrobial soap or phosphate buffered 0.25% hypochlorite solution (dilute Dakin's solution). This antimicrobial irrigation reduces septic episodes and hypermetabolic sequelae, and improves subsequent skin graft survival. Biological Dressing Fresh skin allograft (also called homograft) has become the 'gold standard' for temporary coverage of the clean open burn wound. Allograft achieves an environmental 'seal' of the burn wound at the graft-wound interface and improves host immune defenses. Allogenous human skin graft can be obtained from fresh cadavers within 18 hours of death or from living relatives to assure that skin cells within the graft are viable. The graft can re-vascularize once adhered to the wound. Allograft provides the best temporary closure of the excised burn wound. However, the Langerhans cells in the transplanted epidermis retain their antigenicity, and the skin allograft will undergo rejection in 7 to 14 days in normal patients. Immunosuppression of major burn patients increases tolerance of the allograft for up to several weeks, allowing prolonged temporary wound closure awaiting permanent skin autograft. Allograft promotes angiogenesis and maturation in underlying granulation tissue. Healing of subsequent skin autograft can be anticipated in areas of good allograft 'take'. However, fresh skin allograft has a high price tag, a limited supply, a short shelf life (2-3 weeks), and a need for refrigerated storage. Although shelf life may be improved by freezing or lyophilization, these processes diminish cell viability, graft adherence, and protective functions of the altered allograft. Fresh skin allograft should only be used on clean wounds where graft 'take' is anticipated. Amnion is readily available from the delivery suite and is inexpensive. However, it adheres poorly to the wound and must be covered by an occlusive dressing. Although amnionic coverage can promote angiogenesis and increased wound capillary density, its use in burns has become disfavored. Porcine xerograph (heterograft)
is nonviable, adheres less than allograft, and does not undergo However, pigskin is
well-suited for temporary coverage of full and partial-thickness burn
wounds. Pigskin is cheaper and more available than allograft.
Its recommended uses include protective coverage of partial-thickness wounds
to allow spontaneous healing, temporary coverage of clean granulating wound
beds between autografting procedures, and to serve as a 'test graft' to
decide suitability for autograft closure. Pigskin should not be used
on densely contaminated or Synthetic biological dressings also provide wound protection from dessication and contamination, increase the rate of wound healing, and reduce patient discomfort. Good wound adherence is needed for success as intervening necrotic tissue or serum results in infection. Diligence in application is essential. When used to cover clean partial-thickness wounds, the dressing detaches as re-epithelialization and keratinization occurs underneath. Biobrane©
is a synthetic, bilaminate membrane with an outer semi-permeable silicone
layer bonded to an inner collagen nylon matrix. In-growth of
granulation tissue into the inner Biobrane
layer increases its adherence. Its elasticity and transparency allows
easy drape ability, fuller range of movement and easy wound inspection.
Biobrane is suited for use on donor sites, superficial partial-thickness
burns, and clean/excised wounds prior to grafting. Biobrane gloves on
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