David W. Mozingo
Albert T. McManus
Basil A. Pruitt Jr.
Infection, the risk of which is proportional to the extent of injury, continues to be the predominant determinant of outcome in thermally injured patients despite improvements in overall care in general and wound care in particular. The control of invasive burn wound infection through the use of effective topical chemotherapy, prompt surgical excision, and timely closure of the burn wound has resulted in unsurpassed survival rates. Even so, infection remains the most common cause of death in these severely injured patients.
Etiology of Burn Injury
Burns are estimated to affect 1.25 million people in the United States annually [1]. Of this number, 50,592–68,488 patients require hospital admission, 20,000–25,000 of whom have injuries of such significance that care is best undertaken in a burn center. House and structure fires are responsible for >70% of the yearly 3,785 burn-related deaths, 75% of which result from smoke inhalation or asphyxiation and 25% are due to burns. However, these fires are responsible for only 4–5% of burn admissions. Injuries due to contact with flame or ignition of clothing are the most common cause of burn in adults whereas scald burns are most common in children. The majority of patients sustain burns of such limited severity and extent (>80% of burns involve <20% of the body surface) that they can be treated on an outpatient basis. Approximately 170–230 patients per million population per year require hospital admission owing to the extent of their burns or to other complicating factors. Approximately 33% of patients who require in-hospital care have a major burn injury—as defined by the American Burn Association on the basis of burn size, causative agent, oxpreexisting disease, and associated injuries—and should be treated in a tertiary care burn center [2].
Changes in wound care over the past 40 years, including the use of effective topical antimicrobial chemotherapy and excision of the burned tissue to achieve timely closure of the burn wound, have significantly reduced the occurrence of invasive burn wound infection and its related morbidity and mortality. Regular collection of cultures from patients permits early identification of the causative pathogens of those infections that do arise. Moreover, infection control procedures, including strict enforcement of patient and staff hygiene and use of patient isolation methods, have been effective in controlling the spread of resistant organisms and eliminating them from the burn center. These advances and the improvements in the general care of critically ill burn patients have resulted in markedly improved survival rates. However, as a manifestation of the systemic immunosuppressive effects of burn injury, infection at other sites, predominantly the lungs, remains the most typical cause of morbidity and death in these severely injured patients (Figure 36-1).
Host Immune Function
Thermal injury initiates a deleterious pathophysiologic response in every organ system with the extent and duration of organ dysfunction proportionate to the size of the
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burn. Direct cellular damage is manifested by coagulation necrosis with the depth of tissue destruction determined by the duration of contact and the temperature to which the tissue is exposed. Following a burn, the normal skin barrier to microbial penetration is lost, and the moist, protein-rich avascular eschar of the burn wound provides an excellent culture medium for microorganisms. While destruction of the mechanical barrier of the skin contributes to the increased susceptibility to infection, postburn alterations in immune function also could be of significant importance. Every component of the humoral and cellular limbs of the immune system appears to be affected after thermal injury; the magnitude and duration of dysfunction are proportional to the extent of injury.
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Figure 36-1 The frequency of infection by site expressed as a percentage of all infections complicating thermal injury. (From United States Army Institute of Surgical Research, 1991–1995.) |
During the first weeks after injury, the total white blood cell count is elevated, but peripheral blood lymphocyte counts decrease. Alterations in lymphocyte subpopulations, including reversal of the normal ratio of T-helper cells to T-suppressor cells, have been described [3,4]. Delayed hypersensitivity reactions and peripheral blood lymphocyte proliferation in the mixed lymphocyte reaction are both inhibited following burns. Alterations in interleukin-2 ox(IL-2) production and IL-2 receptor expression by lymphocytes have been observed with burn injury; a direct correlation has been established between the extent of the burn and the decline of IL-2 production by peripheral lymphocytes [5].
Increased numbers of circulating B lymphocytes are evident early in the postburn course; however, serum immunoglobulin G (IgG) levels decline after burn injury and gradually return to normal over the succeeding 2 to 4 weeks. The association of higher numbers of circulating B cells but reduced serum levels of IgG suggests a defect in the ability of B cells to generate a normal response after burn injury [6]. Similar findings have been observed in IgM-producing cells isolated from murine mesenteric lymph nodes and spleens following burns [7]. Exogenous administration of IgG to burn patients has been shown to promptly restore normal IgG levels but exerts no demonstrable effect on the incidence or outcome of infections [8].
Burn injury induces a severity-related shift in the maturity of circulating granulocytes that continues for several weeks after injury. Alterations in granulocyte function, including those of chemotaxis, adherence, degranulation, oxygen radical production, and complement receptor expression, have been identified [9]. Granulocytes isolated from burn patients exhibit increased cytosolic oxidase activity and greater than normal oxidase activity after in vitro stimulation, suggesting that these neutrophils are primed and capable of producing more tissue and organ injury [10]. Recent investigations have verified elevations of F-actin content and impaired ability to polymerize F-actin in the granulocytes of burn patients when compared with those of controls [11]. These alterations can in part be responsible for the observed changes in chemotaxis and migration after thermal injury.
Etiology of Burn Wound Infection
Both the nature of the burn wound and microorganism-specific factors influence the rate of microbial proliferation in and penetration of the burn eschar. Burn tissue, rich in coagulated protein and well hydrated by the transeschar movement of fluid and serum, creates an excellent microbial culture medium. The eschar is avascular owing to thermal thrombosis of nutrient vessels, limiting both the delivery of systemically administered antibiotics and the migration of phagocytic cells into the burned tissue. Bacterial proliferation in the wound also can be enhanced by such factors as wound maceration, pressure necrosis, and wound desiccation with neoeschar formation. In addition, secondary impairment of blood flow to the wound could further predispose the patient to invasive infection by curtailing the delivery of oxygen, nutrients, and phagocytic cells to the viable subeschar tissue.
The character of the microbial flora of the burn wound changes with time. The gram-positive organisms that predominate in the early postburn period are replaced by gram-negative organisms by the second week. Without the application of topical antimicrobial agents, the density of bacteria grows progressively, and the microorganisms penetrate the eschar by migration along sweat glands and hair follicles until they reach the eschar/nonviable tissue interface. Additional microbial proliferation occurs in the subeschar space, enhancing the lysis of denatured collagen and sloughing the eschar. If the density and invasiveness of the microorganisms exceed the host's defense capacity, proliferating organisms in the subeschar space can invade the underlining viable tissue, leading to invasive burn wound infection and even systemic spread to remote tissues and organs. Bacterial invasion is uncommon unless
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the number of microorganisms exceeds 105/grams (g) of biopsy tissue.
Certain strain-specific factors also appear to be important in the pathogenesis of invasive burn wound infection. The production of enzymes, such as collagenase, elastase, protease, and lipase, can enhance the organisms' ability to penetrate the eschar. Moreover, bacterial motility and antibiotic resistance appear to be important in the development of invasive infection. Effective topical antimicrobial chemotherapy limits intraeschar bacterial proliferation and the attendant risk of invasive infection.
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Figure 36-2 Photomicrograph of a burn wound biopsy specimen showing hyphae typical of Aspergillus species present in unburned tissue. The perivascular location of the hyphal element indicates stage IIC invasion. |
Histologic Staging of Burn Wound Colonization and Infection
The presence of microorganisms in the nonviable burned tissue, termed colonization, is a distinctly different entity from the presence of microorganisms in viable tissue beneath the burn eschar, termed invasive burn wound infection. Histologic examination of a biopsy of the burn wound and underlying viable tissue is the most rapid and reliable method for differentiating microbial colonization from invasive infection [12]. Burn wound biopsy is performed as an intensive care unit or ward procedure. An elliptical biopsy (0.5×1.0 centimeters), which includes the subjacent unburned viable tissue, is obtained by scalpel dissection from an area of burn wound suspected of being infected. Hemostasis is easily achieved by the application of direct pressure or by electrocoagulation. One-half of the specimen is cultured to identify microorganisms and their antibiotic sensitivities. The remaining half is submitted to the pathology laboratory for histologic examination. Using the rapid section technique, results are available in 3–4 hours, whereas a frozen-section technique can yield a diagnosis in 30 minutes, albeit with an attendant 4% falsely negative diagnosis rate [13]. The presence of microorganisms in viable tissue confirms the diagnosis of invasive burn wound infection (Figure 36-2). When the organisms are confined to the necrotic eschar or there is suppuration in the subeschar space separating nonviable from viable tissue, the wound is considered to be colonized, not infected (Figure 36-3). Table 36-1 presents a histologic staging scheme for burn wound colonization and infection.
Surface cultures of the burn eschar cannot distinguish colonization from invasive infection. Although commonly used in clinical practice, quantitative bacteriologic cultures of the burn wound correlate poorly with the presence of invasive burn wound infection. When bacteriologic counts are <105/g of biopsy tissue, invasive burn wound infection rarely is present; however, even when quantitative
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counts exceed 105 organisms/g, histologic examination confirms the presence of invasive infection in <50% of such specimens. Burn wound biopsies can at times yield misleading results but less commonly than wound cultures. Failing to include viable subeschar tissue in the biopsy specimen or sampling of a noninfected area can limit the usefulness of this technique. Negative biopsy results in the presence of clinical deterioration necessitate reexamination of the burn wound and procurement of biopsy material from other areas when other sources of systemic infection have been discounted.
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Figure 36-3 Photomicrograph of a burn wound biopsy specimen showing dense inflammatory cell accumulation at the interface of the viable tissue to the right and the nonviable tissue to the left. Branched hyphal elements are localized in this area, indicating stage IC colonization (arrow). |
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TABLE 36-1 |
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Burn Wound Microbial Flora
Over the past 20 years, significant changes in the microbial ecology of the burn wound have been noted. The recovery of Pseudomonas and other gram-negative bacteria, which were once the most common organisms causing burn wound infection, has markedly declined with improvements in the isolation of patients [14]. Consequently, invasive Pseudomonas burn wound infection has essentially disappeared as a complication of burn patients treated in tertiary burn centers [15]. Tables 36-2 and 36-3 review all burn wound biopsy results in general and those demonstrating invasive burn wound infection in particular, respectively, during a recent 5-year period at the U.S. Army Institute of Surgical Research and confirm this fact. Patients who have received broad-spectrum antibiotics for perioperative coverage or treatment of septic complications and whose wounds remain open for many days owing to the extent of the burn are at increased risk of burn wound colonization and infection by yeasts, fungi, and multiple antibiotic-resistant bacteria. The true fungi have replaced bacteria as the most common microbes causing burn wound infection in recent years [16]. This predominance of fungal wound infections
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must be viewed in the context of the marked overall decline in wound infections. Moreover, improperly cared for and neglected burn wounds have the same high risk of bacterial infection as was common in this country several decades ago.
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TABLE 36-2 |
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Viral burn wound infections are relatively uncommon and usually are caused by herpes simplex virus type 1 (see Chapter 42) [17]. Recently healed or healing partial-thickness burns, particularly those in the nasolabial area, are most frequently affected. The appearance of serrated crusted lesions, particularly on the lips, is characteristic of viral infection. Diagnosis is made by histologically examining biopsy material or scrapings from the cutaneous lesions. Applications of topical 5% acyclovir ointment every 3 hours for 1 week has been reported to shorten the time to heal these lesions, the duration of associated pain, and the duration of viral shedding. Even without treatment, these infections usually are self-limited and of little or no systemic consequence. However, if systemic signs and symptoms of disseminated infection are present, such as unexplained sepsis and/or unrelenting fever, the diagnosis of disseminated viral infection should be entertained.
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TABLE 36-3 |
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Prevention of Burn Wound Infection
Progress in the general care of the critically burned patient emphasizes preventing infectious complications. These efforts have focused mainly on the areas of environmental control (through single-bed rooms and other forms of isolation) and topical antimicrobial prophylaxis of the burn wound. Effective infection control programs are essential to reduce the exposure of patients in critical care units to healthcare-associated infection (HAI) pathogens. Such control includes strictly enforced hand hygiene, gowning, and gloving policies. When new endemic microbial strains are identified, prevention of patient-to-patient spread and unit environmental contamination can be accomplished using patient cohorting (seeChapters 13 and 26). Cohorting, which entails the assignment of patient care personnel in teams to provide care for only a specific patient or only patients colonized or infected with a targeted organism limits the spread of and can even eliminate antibiotic-resistant endemic organisms [18].
Effective infection control programs for burn centers should include scheduled microbial surveillance of colonization of patients, environmental hygiene–monitoring procedures (seeChapter 20), biopsy assessment of the microbial status of the burn wound as necessary, monitoring of the incidence and causes of infection, and timely review of culture and clinical data by the infection control team (see Chapter 5). The patient colonization surveillance program typically includes thrice weekly cultures of sputum and the burn wound surface and twice weekly cultures of urine and stool. The determination of a panel of antibiotic sensitivities for the predominant isolated organisms or targeted organisms aids in the recognition of problems with cross-contamination and introduction of multiply resistant bacterial strains into the unit's usual flora. Strict criteria for the definition and identification of infections that occur in burn patients are necessary to avoid nonessential and inappropriate antibiotic use. To minimize the emergence of microbial resistance, antibiotics are used in general only for specific indications. Effective infection control policies require continual reevaluation of surveillance culture results and correlation with the sites and treatment of infections. Prompt institution of effective infection control practices is required when cross-contamination and/or other breaches in infection control are identified through these surveillance programs.
Patient isolation in single-bed rooms has been shown to lower the incidence of cross-contamination and subsequent infections complicating the hospital course of
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burn patients [19]. In general, the air flow patterns of the isolation rooms are probably not as important as the prevention of patient-to-patient contact. However, positive air flow design can delay colonization by HAI flora. Negative air flow rooms in burn centers are generally reserved for patients with infections spread by the airborne route (e.g.,Mycobacterium tuberculosis) that could be hazardous to other patients and hospital staff members (see Chapter 33).
Burn Wound Hygiene and Topical Antimicrobial Therapy
Care of the burn wound begins at the accident scene by covering it with clean sheets or blankets to preserve body temperature and prevent continued environmental exposure. In the absence of gross contamination, burn wounds can be treated safely without topical antimicrobial agents for the first 24–48 hours. When a burn patient arrives at the definitive care facility, initial burn wound debridement should be performed. General anesthesia is not necessary; intravenous analgesia is sufficient for pain control during this procedure. The burns are gently cleansed with a surgical detergent disinfectant, and nonviable epidermis is debrided. Bullae should be excised and body hair shaved from the area of thermal injury beyond the margin of normal skin. The patient is placed in a clean bed, and bulky dressings can be positioned beneath the burned parts to absorb the often copious serous exudate. These dressings should be changed when they become saturated or soiled, and patients should be turned frequently to prevent maceration of burned and unburned skin. The initial debridement and daily cleansing with an antimicrobial-containing surgical scrub is best performed in a shower area using a handheld shower head with the patient lying on a disposable plastic sheet-covered litter or specially designed shower cart. Alternatively, the patient can be placed on a slanted plinth suspended over a physical therapy tank. Immersion hydrotherapy is not necessary and can serve only to disseminate the fecal flora or other contaminating organisms over the entirety of the burn wound. For patients whose general condition is too critical to permit movement to a shower area, daily wound care can be carried out at the bedside. Following cleansing and debridement, the topical antimicrobial agent of choice is applied.
Mafenide acetate (Sulfamylon), silver sulfadiazine (Silvadene), and silver nitrate are the three most commonly employed topical antimicrobial agents for burn wound care. Each agent has specific limitations and advantages with which the physician must be familiar to ensure the patient's safety and optimal benefit. Mafenide acetate and silver sulfadiazine are available as topical creams to be applied directly to the burn wound whereas silver nitrate is applied as a 0.5% solution in occlusive dressings. Either cream is applied in a 1/8-inch layer to the entire burn wound in an aseptic manner after initial debridement and reapplied at 12-hour intervals or as required to maintain continuous topical coverage. Once daily, all of the topical agents should be cleansed from the patient using a surgical detergent disinfectant solution and the burn wounds examined by the attending physician. Silver nitrate is applied as a 0.5% solution in multilayered occlusive dressings that are changed twice each day.
Mafenide acetate burn cream is an 11.1% suspension in a water-soluble base. This compound diffuses freely into the eschar owing to its high degree of water solubility. Sulfamylon is the preferred agent if the patient has heavily contaminated burn wounds or has had burn wound care delayed by several days. Sulfamylon has the added advantage of being highly effective against gram-negative organisms, including most Pseudomonas species. Physicians using this agent must be aware of several potential clinical limitations associated with its use. Hypersensitivity reactions occur in 7% of patients, and pain or discomfort of 20–30 minutes duration is common when it is applied to partial-thickness burn wounds. This agent also inhibits carbonic anhydrase, and a diuresis of bicarbonate often is observed after its use. The resultant metabolic acidosis could accentuate postburn hyperventilation, and significant acidemia could develop if compensatory hyperventilation is impaired. Inhibition of this enzyme rarely persists for >7 to 10 days, and the severity of the acidosis can be minimized by alternating applications of Sulfamylon with silver sulfadiazine cream every 12 hours.
Silver sulfadiazine burn cream is a 1% suspension in a water-miscible base. Unlike Sulfamylon, Silvadene has limited solubility in water and, therefore, limited ability to penetrate into the eschar. The agent is most effective when applied to burns soon after injury to minimize bacterial proliferation on the wound's surface. This agent is painless upon application, and its use does not affect serum electrolytes and acid-base balance. Hypersensitivity reactions are uncommon; an erythematous maculopapular rash subsides on discontinuation of the agent. Silver sulfadiazine occasionally induces neutropenia by a mechanism thought to involve direct bone marrow suppression; white blood cell counts usually return to normal following discontinuation [20]. With continual use, resistance to the sulfonamide component of silver sulfadiazine is common, particularly in certain strains of Pseudomonas and manyEnterobacter species. However, the continued sensitivity of microorganisms to the silver ion of this compound has maintained its effectiveness as a topical antimicrobial agent.
A 0.5% silver nitrate solution has a broad spectrum of antibacterial activity imparted by the silver ion. This agent does not penetrate the eschar because the silver ions are rapidly precipitated on contact with any protein or cationic material. Use of this agent is not associated with more intense wound pain except from the mechanical action required for dressing changes. The dressings, which are changed twice daily, are moistened every 2 hours with the silver nitrate solution to prevent evaporation from increasing the silver nitrate concentration to cytotoxic levels within
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the dressings. Transeschar leaching of sodium, potassium, chloride, and calcium should be anticipated, and these chemical constituents should be appropriately replaced. Hypersensitivity to silver nitrate has not been described. Mafenide acetate, silver sulfadiazine, and 0.5% silver nitrate are effective in preventing invasive burn wound infection; however, because of their lack of eschar penetration, silver nitrate soaks and silver sulfadiazine burn cream are most effective when applied soon after burn injury.
Recently, many silver-containing dressings have become available and are marketed as antimicrobial barrier dressings. Some have the indication to be used on second degree burns. Also, most of these dressings can be left on the wounds for several days. Like silver nitrate, the bacteriocidal properties of silver are responsible for the antimicrobial nature of these dressings but are not indicated for use on full-thickness burns. There is no indication that silver is absorbed significantly into the burn. When using dressings that can be left in place for more than 1–2 days, it is essential to ascertain that the wounds indeed are partial thickness in nature and that healing would be expected to occur within 1–3 weeks. A serious burn wound infection could occur beneath an occlusive dressing left in place for an extended period on a full-thickness burn.
The acceptance and widespread appliance of prompt burn wound excision in the early care of burn patients also has contributed to the decreased incidence of bacterial burn wound infection. Surgical excision and split-thickness skin grafting of burns diminish the time during which the wound is at risk of invasive infection. In patients with burns of <40% of the total body surface, excision is associated with shorter hospital stays, and the burn wounds can be definitively grafted in one or two surgical procedures [21]. In patients with burns over ≥40% of the total body surface, burn wound excision can shorten the duration and magnitude of injury-related physiologic stress and the subsequent degree of immunologic impairment. As soon as the initial burn resuscitation is complete and the patient is physiologically stable, burn wound excision can be initiated in staged procedures so that the entirety of the full-thickness or deep partial-thickness wounds can be removed within several weeks. When skin donor sites are not available for complete grafting of these wounds, a variety of skin substitutes and biologic dressings can be used as a bridge to complete wound coverage. The exact contribution of surgical treatment to the decline in incidence of invasive bacterial burn wound infection has not been well documented; however, the temporal relationship cannot be ignored.
Clinical Diagnosis of Burn Wound Infection
Burn wound infection occurs most commonly in patients in whom the extent of burn exceeds 30% of the body surface and in those who have suffered skin graft failure that left an open wound. Successful treatment of burn wound infection requires early detection; therefore, it is mandatory that the entire wound be examined daily to detect changes in appearance. The clinical signs of invasive burn wound infection often are indistinguishable from those observed in uninfected hypermetabolic burn patients or in burn patients with other forms of sepsis. These findings can include hyper- or hypothermia, tachycardia, tachypnea, ileus, glucose intolerance, and disorientation. Physical and tinctorial changes in the appearance of the burn wounds are more reliable signs of invasive burn wound infection (Table 36-4). Conversion of an area of partial-thickness burn to full-thickness necrosis and the appearance of focal areas of dark hemorrhagic or black discoloration are the most commonly noted changes indicative of burn wound infection (Figure 36-4). The development of clinical signs and symptoms of sepsis in the thermally injured patient should prompt a thorough examination of the burn wound to identify areas suspected of harboring invasive infection. Confirmation of the diagnosis of burn wound infection is made by histologic examination of a biopsy specimen as previously described.
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TABLE 36-4 |
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The emergence of nonbacterial opportunists as the major pathogens invading the burn wound has resulted in changes in the classic clinical presentation of burn wound infection.Candida spp. rarely invade the wound to cause systemic infection. However, Candida spp. infection can arise in the interstices of a meshed skin graft and in an excised burn wound that remains unclosed as a consequence of the loss of a skin graft or a biologic dressing. Filamentous fungi are more aggressive invaders of the burn wound and could cause severe infection. These fungi rarely traverse fascial planes and remain confined to the subcutaneous tissues. Aspergillus spp. can be detected as colonizers and occasionally as invaders of the burn eschar by histopathologic examination of burn wounds at the time of excision and skin grafting. The clinically relevant infections occur, however, relatively late in the hospital course of patients with extensive burns who have already undergone multiple operative procedures (for which they have received perioperative broadspectrum antibiotics) and
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still have unexcised eschar or previously excised, ungrafted open wounds. These infections often resemble a colony of mold with a somewhat fuzzy texture, appearing in a skin graft interstice or an area of open wound. This surface appearance often is accompanied by subcutaneous burrowing tunnels filled with the invading fungus and detected at the time of surgical debridement.
The phycomycetes are typically aggressive, spreading rapidly along tissue plains, traversing fascia, and invading blood vessels and lymphatics [22]. Infections caused by these organisms are characterized by expanding soft-tissue ischemic necrosis with a peripheral edematous rim and, frequently, hematogenous dissemination to remote sites. The diagnosis is confirmed, as with bacterial burn wound infection, by histologic examination of a biopsy specimen.
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Figure 36-4 Multiple areas of dark discoloration on the thigh and buttocks of this patient, accompanied by unexpectedly rapid eschar separation, characteristic of burn wound infection. |
Treatment of Burn Wound Infection
The treatment of burn wound infection is initiated upon histologic confirmation of the presence of microorganisms in viable tissue. If only colonization (stage 1A to stage 1C) is present, no specific change in antimicrobial therapy is indicated unless serially obtained biopsy specimens document progression of the colonization stage. If stage 2 (invasion) is observed, prompt treatment for invasive burn wound infection should begin. In the case of bacterial burn wound invasion, topical twice-daily applications of mafenide acetate should be used. The eschar-penetrating ability of this agent extends the antimicrobial activity throughout the depth of the burn eschar. Systemic antibiotic therapy is initiated based on previous burn wound surveillance cultures and burn center organism prevalence. Additional refinements in antibiotic treatment are based on the individual patient's wound culture and sensitivity results. Supportive critical care is employed to maintain hemodynamic and respiratory stability, as it is for other severely ill patients.
Injection of an antibiotic solution into the subcutaneous tissue beneath the eschar (subeschar clysis) is recommended before surgical excision of an infected burn wound to minimize the risk of hematogenous seeding and precipitation of florid septic shock [23]. Half of the daily dose of a broad spectrum antipseudomonal penicillin, such as piperacillin or ticarcillin, delivered in 1 liter of normal saline is infused into the subeschar tissues using a no. 20 spinal needle to minimize the number of injection sites. The patient is prepared and scheduled for surgical excision of the infected tissue within the next 6–12 hours, and the subeschar clysis is repeated immediately before surgery.
Excision of the burn wound to the level of the investing muscle fascia ensures complete removal of all nonviable infected tissue. After excision of the burn, the wound is treated with moist dressings containing an antimicrobial agent, such as 0.5% silver nitrate solution (the authors use a 5% mafenide acetate solution, which is not generally available). Alternatively, a biologic dressing can be applied if all nonviable tissue has been removed and the exposed tissue appears to be uninfected. The patient is returned to the operating room in 24 to 48 hours; at that time, the wound is inspected, and redebridement or split-thickness skin grafting can be performed as needed.
The treatment for candidal or fungal burn wound infection is similar to that of invasive bacterial infection. Infection or new colonization of previously excised or grafted
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wounds requires treatment by twice-daily application of a topical antifungal agent, such as clotrimazole cream or ciclopiroxolamine cream. Such treatment usually controls surface colonization. However, if the superficial infection continues to extend or the fungal infection is shown to involve deep tissue, such as fascia or muscle, if it has invaded the microvasculature of underlying viable tissue, or if it is associated with systemic signs of sepsis, parenteral administration of amphotericin B should be initiated. The infected tissue must be widely debrided and treated with a topical antifungal agent applied beneath occlusive dressings, which should be changed two to three times daily. The patient is returned to the operating room 24–48 hours later for further debridement and closure of the burn wound by autografting or applying a biologic dressing as dictated by the adequacy of the initial debridement.
Infections of Special Concern
Clostridium Tetani
Tetanus, caused by the neurotoxin of Clostridium tetani, an anaerobic, gram-positive, spore-forming rod ubiquitous in soil and the gastrointestinal tracts of humans and animals, has been reported as a rare complication of thermal injury. This organism thrives in hypoxic wounds and necrotic tissue, both of which exist in the full-thickness burn. The diagnosis of tetanus is based on characteristic physical findings because wound cultures often fail to detect the causative organism. The usual initial signs and symptoms are severe trismus with stiffness of the paraspinous and abdominal musculature. Localized or generalized muscle spasm, dysphagia, and laryngospasm can develop; the disease can progress to involve more muscle groups, causing generalized rigidity. Ventilation can be impaired by involvement of the diaphragm, chest, and abdominal musculature. Severe episodes require endotracheal intubation and mechanical ventilation. Treatment is mainly supportive and involves aggressive critical care management of the hemodynamic and respiratory systems.
When the diagnosis is made, tetanus immune globulin should be administered immediately to neutralize any circulating free exotoxin. The usual dose is 3,000 to 6,000 (u) given intramuscularly. Intravenous penicillin G (10–40 million u per day) should be given to eradicate the clostridial organisms. Uncontrolled muscle spasms can lead to rhabdomyolysis and skeletal fractures. Morphine, magnesium sulfate, and epidural anesthesia all have been used to reduce muscle spasticity. Sedation with benzodiazepines or barbiturates could be necessary, and, in severe cases, neuromuscular blockade could be required.
Fortunately, tetanus is readily prevented. During the initial care of the burn patient, the patient's tetanus immunization status should be determined. The burn patient who has been immunized against tetanus should be given a booster dose of tetanus toxoid if the last dose was administered >5 years earlier. Patients with no history or an uncertain history of active immunization should receive tetanus immune globulin in addition to the initial dose of tetanus toxoid. Active immunization is subsequently completed according to the routine dosage schedule.
Staphylococcus aureus
Toxin-producing Staphylococcal spp. have been isolated from both colonized and infected burn wounds and other sites of infection [24,25] (see Chapter 41). The emergence of gram-positive organisms as the predominant flora in burn patients has contributed to a lessening in the impact of infection; the virulence of Staphylococcus aureus can be strain specific, and bacteremia resulting from strains possessing the gene for the production of toxic shock syndrome toxin has been associated with episodes of unexplained profound hemodynamic instability. This gene, however, has been identified in staphylococcal strains recovered from patients with wound colonization, bacteremia, and other infections without evidence of profound physiologic disturbance.
The diagnosis of a variant of the toxic shock syndrome should be considered in thermally injured patients with staphylococcal infections who manifest hemodynamic instability that responds poorly to treatment and that is out of proportion to what is usually encountered in gram-positive infections. Initial treatment requires aggressive intravenous fluid resuscitation to restore hemodynamic stability. Vancomycin should be administered intravenously unless the organism is known to be sensitive to methicillin when a β-lactamase-resistant antistaphylococcal antibiotic, such as nafcillin, can be given.
At present, an antitoxin to the toxic shock syndrome toxin 1 is not available. Approximately 90% of the general population has antibodies against the toxin, but nearly all patients with toxic shock syndrome related to menstruation have had undetectable antibodies at the onset of the disease. Although this relationship has not been confirmed in thermally injured patients thought to have the variant toxic shock syndrome, the isolation of a strain of S. aureus producing the toxic shock syndrome toxin 1 and the absence of circulating antibodies to the toxin could help establish the definitive diagnosis.
Antibiotic-resistant bacteria of special note and the subject of much controversy are the methicillin-resistant strains of S. aureus (MRSA) (see Chapters 15 and 41). Since the 1960s, these strains have been reported and treated as if they were distinct pathogens with more virulence than other methicillin-sensitive strains. Undoubtedly, the emergence of antibiotic-resistant organisms is of concern, and efforts should be made to limit their inroads. However, the unique concern about MRSA in particular has resulted in temporary closure of burn and other intensive care facilities and restriction of patients' movements among levels of care.
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The benefits of these practices must always be weighed against their clinical, epidemiologic, and economic value.
The virulence and pathologic significance of MRSA compared with methicillin-sensitive strains causing infections in burn wound patients were evaluated in a 1989 study [26]. Colonization with any strain of staphylococcus was identified in 658 burn patients treated during a 6-year period; of this total, 319 (or nearly half) of these patients were colonized with MRSA. In this group, a total of 253 staphylococcal infections occurred in 178 patients: 58% of infections were pulmonary and 38% were bacteremias. In 58/178 patients, infections were caused by MRSA. The outcomes of patients infected with MRSA and methicillin-sensitive strains of Staphylococcus aureus were compared using a multiple logistic regression analysis of mortality. In both groups, all patients were treated with vancomycin, and no differences in the observed and predicted mortality were found between groups. We believe these findings suggest that both MRSA and MSSA in burn patients can lead to serious adverse outcomes. The main concern related to frequent use of vancomycin is the possible development of vancomycin and MRSA resistance prompted by the recent recognition of vancomycin-resistant strains of S. aureus and enterococci (see Chapter 15). Individual centers should adopt strict criteria for diagnosing specific infections in burn patients and specific indications for antibiotic use based on the prevalence of resistant organisms to avoid inappropriate prescription of vancomycin and other antibiotics.
Aeromonas Species
Human infection with Aeromonas spp. most often is associated with either traumatic injuries contaminated with water or soil or with immunosuppression. Infections in burn patients caused by Aeromonas spp. are rare; <20 episodes have been reported in the English literature. A recent report by Barillo et al. describes a series of eight thermally injured patients treated over a 35-year period in whom Aeromonas hydrophila bacteremia developed during their hospital stays [27]. In 6/8 patients, the organism was isolated from wound cultures as well. Aquatic exposure was known or suspected in only 3 of the patients, and 5 of the 8 patients died. In general, soft-tissue infection with Aeromonas spp. has a rapid onset, usually within 48 hours of injury. Subcutaneous abscess formation is common but could not be clinically apparent on initial examination. Infections are usually polymicrobial and accompanied by a foul odor. Aeromonas spp. is particularly destructive of muscle, and necrotizing myonecrosis, resulting in amputation or death, could develop from local infections and hematogenous spread in otherwise healthy individuals. Aeromonas spp. infection can mimic Pseudomonas spp. infection in the formation of ecthyma gangrenosum and can produce gas in soft-tissue planes similar to that seen with clostridial infection.
The treatment of Aeromonas spp. burn wound infection includes systematic antibiotics and surgical intervention. Aeromonas spp. produce β-lactamase and are resistant to penicillins and first-generation cephalosporins. Aminoglycosides, aztreonam, ciprofloxacin, and third-generation cephalosporins usually are effective against these organisms. For the management of burn wound infection, surgical debridement should be accomplished expeditiously as outlined previously.
Summary
Despite significant improvements in the survival of burn patients, infectious complications continue to be the major cause of morbidity and mortality. Control of invasive bacterial burn wound infection by effective topical antimicrobial agents and prompt excision and split-thickness skin grafting of the burn wound clearly is possible with modern burn care. In addition, strict isolation techniques and infection control policies have significantly minimized the occurrence of burn wound infections in general and those caused by gram-negative organisms in particular. In those patients in whom a burn wound infection develops, bacterial infection has been largely supplanted by infection caused by nonbacterial opportunists, namely, fungi and yeasts. Scheduled wound surveillance and microbiologic monitoring with the use of wound biopsies to provide histologic confirmation of burn wound infection permits prompt diagnosis of microbial invasion at a stage when timely institution of antibiotic therapy and surgical intervention can save the patient.
References
P.609