Treatment of infection in burns

Introduction

Infections remain a leading cause of death in burn patients. For patients with burn size greater than 40% TBSA, 75% of all deaths are due to infection [1]. Many features unique to burn patients make diagnosis and management of infection especially difficult. Burn injury represents the most extreme endpoint along the spectrum of traumatic injury and as such is associated with profound alterations in host defense mechanisms and immune function. These derangements predispose thermally injured patients to local and systemic invasion by microbial pathogens.

The burn wound represents a susceptible site for opportunistic colonization by organisms of endogenous and exogenous origin. A broad variety of patient factors such as age, immunosuppressed status, extent of injury, and depth of burn in combination with microbial factors such as type and number of organisms, enzyme and toxin production and motility determine the likelihood of invasive burn wound infection. Burn wound infections can be classified on the basis of the causative organism, the depth of invasion, and the tissue response. Diagnostic procedures and therapy must be based on an understanding of the pathophysiology of the burn wound and the pathogenesis of the various forms of burn wound infection.

The purpose of this chapter is to depict the diagnosis and management of burn wound infections,

Marc G. Jeschke et al. (eds.), Handbook of Burns

helping to provide the burn surgeon with a clinical guide to assist in clinical judgment.

Clinical management strategies

Many of the clinical signs and symptoms used to diagnose infection in other settings are unreliable in the burn intensive care unit since they are often present even in the absence of true underlying infection. Advances in critical care such as earlier resuscitation and support of the hypermetabolic response have decreased burn mortality, but infections are still pervasive in severely burned patients and account for significant morbidity and mortality.

With regards to burn wound infection, the cornerstone of management continues to be aggressive early debridement of devitalized and infected tissue. Unfortunately, burn patients are rapidly colonized by nosocomial pathogens and foci of invasive infection must be identified and treated quickly with appropriate antimicrobial therapy. Additionally, other potential foci for invasive infection include the tracheobronchial tree, the lungs, the gastrointestinal tract, central venous catheters and the urinary tract. Once an infection is disseminated hematogenously and becomes established in a burn patient, it is very difficult to eradicate, even with large does of broad-spectrum antimicrobial therapy. Traditional thinking would argue for beginning broad-spectrum coverage at the first

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signs of infection and then narrowing the coverage as results of cultures come back. While this is clearly true for many critical ill patients, burn represents a unique situation, which may merit more aggressive management. New emerging strains of multiresitant organisms represent an ominous threat in the burn unit and monotherapy with conventional antimicrobials may be inadequate for some infections.

Time-related changes in the predominant flora of the burn wound from gram-positive to gram-neg- ative recapitulate the history of burn wound infection. Treatment with two or more agents is becoming necessary in the management of these gram-nega- tive invasive infections. Selection and dissemination of intrinsic and acquired resistance mechanisms increase the probability of burn wound colonization by resistant species such as Pseudomonas aeruginosa. Even so, effective topical antimicrobial therapy and early burn wound excision have significantly reduced the overall occurrence of invasive burn wound infections, individual patients, usually those with extensive burns in whom wound closure is difficult to achieve, may still develop a variety of bacterial and nonbacterial burn wound infections. Consequently, the entirety of the burn wound must be examined on a daily basis by the attending surgeon. Any change in wound appearance, with or without associated clinical changes, should be evaluated by biopsy. Quantitative cultures of the biopsy sample may identify predominant organisms but are not useful for making the diagnosis of invasive burn wound infection. Histologic examination of the biopsy specimen, which permits staging the invasive process, is the only reliable means of differentiating wound colonization from invasive infection. Identification of the histologic changes characteristic of bacterial, fungal, and viral infections facilitates the selection of appropriate therapy. A diagnosis of invasive burn wound infection necessitates change of both local and systemic therapy and, in the case of bacterial and fungal infections, prompt surgical removal of the infected tissue. Even after the wounds of extensively burned patients have healed or been grafted, burn wound impetigo, commonly caused by Staphylococcus aureus, may occur in the form of multifocal, small superficial abscesses that require surgical debridement. Current techniques of burn wound care have significantly reduced the incidence of invasive burn wound

infection, altered the organisms causing the infections that do occur, increased the interval between injury and the onset of infection, reduced the mortality associated with infection, decreased the overall incidence of infection in burn patients, and increased burn patient survival.

Pathophysiology of the burn wound

Thermal injury is associated with a state of generalized immunosuppression which is characterized by an impairment of host defense mechanisms and defects in humoral and cell-mediated immunity. There are several specific alterations in host defense which are intrinsic to the burn injury itself and which predispose these patients to microbial invasion. The most important intrinsic factor is breach of the mechanical barrier provided by the skin. The primary injury in burns results in irreversible tissue necrosis at the center of the burn due to exposure to heat, chemicals, or electricity. The extent of this injury is dependent on the temperature (or concentration) and the duration of exposure as well as the vascular supply and thickness of the injured skin [2].

A burn wound is characterized by three zones: a central zone of necrosis surrounded by a zone of ischemia and a third peripheral zone of hyperemia characterized by a reversible increase in blood flow [3].

While there is normal resident skin flora, invasive infection is rare through an intact epithelial barrier. The skin has bacteriostatic properties that normally limit the degree of colonization. The local microenvironment is not supportive for growth of microbial pathogens. This changes drastically with a severe burn trauma. The burn wound provides a warm and moist microenvironment in which bacterial proliferation is fostered. Microbial growth is rapid as once non-pathogenic organisms are now allowed to flourish. It is imperative to realize that the most important intrinsic factor is breach of the mechanical skin barrier, since this has implications for the overall approach to infection control. It is the fundamental and primary defect. Antimicrobial therapy and wound care can be viewed as temporizing measures to stave off infection until the primary defect is repaired.

In addition to these alterations in host defense, there are specific defects in humoral and cell-medi- ated immunity that occur following severe burn trauma, including impaired function of natural killer cells. The generalized immunosuppression is further characterized by specific alterations in B and T cell function.

Diagnosis and management of specific infections

Burn wound infection

The diagnosis and treatment of burn wound infection is based on early identification of an infected wound site. Clinically, burn wound infection is most often recognized based on gross appearance or conversion of a partial thickness to a full thickness wound. Most common local sign of invasive burn wound infection is the appearance of focal, multifocal, or generalized dark brown, black, or violaceous discoloration of the wound [4]. The most reliable local sign is conversion of an area of partial thickness injury to full-thickness necrosis or the necrosis of previously viable tissue in an excised wound bed. Other signs of invasive burn wound infection include hemorrhagic discoloration of subeschar tissue, the presence of green pigment (pyocyanin) in subcutaneous fat, edema or violaceous discoloration of unburned skin (or both) at the margin of the burn, and the presence of initially erythematous and later black necrotic nodular lesions (ecthyma gangrenosa) in unburned skin. Local signs characteristic of burn wound infections caused by fungi include unexpectedly rapid separation of the eschar, presumably due to fat liquefaction, and rapid centrifugal spread of subcutaneous edema with central ischemic necrosis [5]. Vesicular lesions in healing or healed second degree burns and the presence of crusted serrated margins of partial-thickness burns of the face, particularly those involving the naso-labial area are characteristic of burn wound infections caused by herpes simplex virus type 1 (HSV- 1)[6]. Once there is clinical suspicion of invasive burn wound sepsis, it is imperative to obtain quantitative wound cultures. Surface cultures are useful for identifying the organisms present on the burn

wound and the predominant members of the burn wound flora, but even quantitative cultures are incapable of differentiating burn wound colonization from burn wound infection. Generally, a low quantitative bacterial count is a good indication that a burn wound infection is not present and wound cultures growing organisms at a quantitative count of greater than 1 × 105 organisms/gram of tissue are considered indicative of a wound at significant risk for invasive sepsis [7]. Thus, due to the limitations of cultures, the histologic examination of a burn wound biopsy is the most reliable and expeditious means of confirming a diagnosis of invasive burn wound infection. The most common pathogens include MSSA and MRSA species and Pseudomonas aeruginosa.

In the case of viral burn wound infections, the diagnosis may also be confirmed by histologic examination of scrapings from the cutaneous lesions. The specific histologic sign of burn wound infection is the presence of microorganisms in unburned tissue. Other histologic findings indicative of burn wound infection are the presence of hemorrhage in unburned tissue, small-vessel thrombosis and ischemic necrosis of unburned tissue, marked inflammatory changes in unburned tissue, dense bacterial growth in the sub-eschar space (a site of microbial proliferation prior to invasion), and intracellular viral inclusions (type A Cowdry bodies) typical for HSV-1 infections.

Generally, maintaining wounds at low contamination levels diminishes the frequency and duration of septic episodes caused by wound flora. This is accomplished by cleansing wound two to three times per day by immersing the wound in cleansing solutions. Some burn facilities still immerse patients in a tub to remove the debris and exudates that has accumulated between dressing changes, however most burn facilities no longer advocate this cleaning technique because of the potential seeding of surface bacteria to the open burn wound of other patients by an inadequately cleaned tube. It is imperative to note that wound cleansing can be painful, cause cooling and might be associated with hematogenous seeding leading to bacteremia. Therefore adequate monitoring is critical with this procedure. The entirety of the burn wound, those areas with intact eschar and those that have been excised, and even those that have been grafted, must be exam-

ined on at least a daily basis. Although donor site infections are rare, they occur most often in patients with massive burns, necessitating that donor sites on such patients be examined each day as well. The wound examination is best performed at the time of the daily burn wound cleansing or dressing change to identify infection in its earliest stages when pharmacologic intervention can control the infection and reduce the associated mortality. Even though topical antimicrobial agents play an important role in decreasing the incidence of burn wound infection, astute clinicians must be aware that antimicrobial therapy is not a substitute for aggressive debridement of grossly infected and devitalized tissue.

When invasive burn wound infection has been diagnosed, general supportive measures are employed to optimize cardiac and pulmonary function and to support other organ systems. Specific systemic antibiotic therapy is instituted based on the current results of the burn center’s microbiology surveillance program and modified thereafter on the basis of the sensitivity tests of the individual patient’s infecting organisms. Wound care must also be altered. If the causative organism is a bacterium, an antimicrobial dressing should be selected. This can range silver containing products such as Acticoat to solutions such as mafenide acetate. Mafenide acetate, which is water-soluble and readily diffuses into the eschar and underlying tissue, can reduce the microbial density of the burn wound and prevent further proliferation of organisms in the eschar and sub-eschar space. Sub-eschar clysis of a broadspectrum penicillin (one-half of the daily dose suspended in 150–1 000 ml saline) can be considered, using a No. 20 spinal needle to minimize the number of infusion sites [20].

Cellulitis

Burn wound cellulitis of bacterial origin can be caused by a variety of organisms, but group A-hemolytic streptococci are the most common offenders [8]. This infection is characterized by erythema, edema and hyperesthesia of unburned skin at the margins of the burn or donor site wound. If untreated, the lesions expand with variable rapidity with or without a lymphangitic component. There may be increased serous exudate from the wound

bed, and if a -hemolytic streptococcal infection involves a skin graft, the graft may be destroyed literally overnight. Progressively expanding cellulitis should be treated with topical application of antimicrobial dressing and systemic penicillin if it is caused by a group A -streptococcus, or a broadspectrum -lactam antibiotic if specific cultures and sensitivity results are not available plus Vancomycin for MRSA coverage [8]. Antimicrobial dressings should be applied to the surface of the donor site until the infection is brought under control, consideration should be given to dressings with MRSA activity. If the donor site is not healed at that time, any open areas can be grafted if the defects are full thickness or covered with a biologic dressing if they are only partial thickness.

Impetigo

Another form of burn wound infection that may occur following burn wound closure or grafting has been termed burn wound impetigo and is characterized by multifocal small superficial abscesses. This infection may lead to extensive destruction of previously adherent skin grafts or ulceration of spontaneously healed partial-thickness burns and healed split-thickness skin graft donor sites. It usually elicits little systemic response, although fever and leukocytosis may occur. The diagnosis, made on the basis of epithelial loss, is confirmed by cultures that commonly show growth of Staphylococcus aureus. Treatment consists in un-roofing all abscesses, meticulous cleansing of the infected areas with a surgical detergent disinfectant, and application of a topical antibacterial ointment, such as mupirocin. A disproportionate systemic response may indicate that the causative Staphylococcus is a producer of toxic shock syndrome toxin 1 (TSST-1), which can be confirmed by toxin assay and should be treated by intravenous administration of vancomycin [26].

Catheter related infections

Infectious complications associated with intravenous and intra-arterial catheters represent a major problem irrespective of the constant attention to aseptic technique for insertion and appropriate maintenance [9]. The burned patient appears to be