Fever in the Burn Patient
Authors: Laurie C. D’Avignon, MD, Clinton K. Murray, MAJ, MC
INTRODUCTION
According to the American Burn Association (ABA), there are 500,000 burn injuries that require medical attention in the US every year (3). The vast majority of these injuries (88%) are a result of residential fires. Approximately 40,000 of those injured require hospitalization. Over 60% of those hospitalized require care in a specialized burn center. It is estimated that 4,000 people die in the U.S. every year as a result of burns. Nearly 75% of these deaths occur before the victim reaches medical care. The remainder later succumb to complications of burn injury. The most frequent complication in the first 24-48 hours post-burn is multiple organ failure syndrome. Multiple organ failure syndrome typically occurs as a result of inadequate fluid resuscitation (26). Fortunately, advances in burn shock resuscitation have led to a marked reduction in mortality within the first 48 hours after injury. Following adequate control of the initial burn related shock, infection emerges as the most common cause of death in these patients. Despite this, the presence of infection can be difficult to diagnose as many of the typical signs of infection, such as fever and tachycardia, overlap with those of the pro-inflammatory state common to all burn injuries.
Historically, fever has been considered a reliable marker of infection though it may occur as a result of inflammatory states induced by a variety of infectious and non-infectious insults. The concept of a systemic inflammatory response syndrome (SIRS) was devised as a way to identify patients with a pro-inflammatory state due to infectious or non-infectious causes (8). The presence of systemic inflammatory response syndrome is defined by the finding of two or more markers of inflammation which include 1) temperature above 38°C or below 36°C, 2) heart rate > 90 bpm, 3) respiratory rate > 20 min or PaCO2 > 32 mmHG and 4) WBC count of >12,000/mm3, or <4,000 mm3 or left shift with >10% bands. Although the precept of systemic inflammatory response syndrome has been widely accepted and applied by the critical care community, it is of limited utility in the burn population because the majority of these patients easily meet systemic inflammatory response syndrome criteria on a daily basis. The alterations in metabolism and physiology that accompany burn injury result in increased temperature, heart rate, respiratory rate and blood pressure. These changes render the definition of systemic inflammatory response syndrome far too inclusive to be useful for predicting the presence of infection or impending sepsis in burn patients (21). In addition, a recent study found that elevated temperature, changes in WBC count and neutrophil percentage are not predictive of bacteremia in burn patients (36). The unique clinical and laboratory derangements associated with burn injury have prompted the American Burn Association (ABA) to advise against the routine use of systemic inflammatory response syndrome criteria in evaluation of the burn patient. The American Burn Association did propose new criteria for the definition of sepsis in these patients in an attempt to distinguish clinical alterations due to infection from those that occur as a result of the burn itself (Table 1) (21).
Epidemiology and Pathophysiology
As previously eluded to, the metabolic and physiologic alterations associated with burn injury frequently result in an elevated temperature. Despite this, infection is always a concern in the febrile burn patients and other clinical findings may prompt an investigation for infectious etiologies. Those patients at highest risk for infection are those with a premorbid diagnosis of diabetes, inhalational injury and total body surface area (TBSA) > 20% (26). Age is not an independent risk factor for infection, however, older patients have a higher all cause mortality (13, 26, 33). The most common infectious complications in burn patients are burn wound infection, pneumonia, and blood stream infection.
Burn Wound Infection
The burn wound results in disruption of the normal barrier function of the skin rendering it highly susceptible to invasion by colonizing bacteria. The incidence of burn wound infection has decreased over the past 30 years, as use of topical antimicrobials, early burn wound excision, and definitive coverage have become standard practice. Although the incidence of infection has declined, the list of offending micro-organisms has not changed significantly (5, 18, 30, 42,47). In the absence of topical antimicrobials, the immediate post-burn period is characterized by rapid colonization of the injured tissue by resident microbial flora (5, 18, 42, 47). Gram positive skin flora, such as Streptococcus pyogenes andStaphylococcus aureus, reside deep within skin appendages and colonize the wound within the first 24 to 48 hours after injury (5, 18). Endogenous gram negative bacteria from the patients’ respiratory and gastrointestinal tract, such asPseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, colonize the wound within the first 48 to 72 hours after injury (5, 18). Micro-organisms may also be transferred to the burn wound from contaminated surfaces, equipment, or on the hands of health care workers (6, 13, 51). The nosocomial transmission of multidrug resistant organisms multidrug resistant organisms, such as extended spectrum beta-lactamase (ESBL) producing K. pneumoniae and drug resistant Acinetobacter calcoaceticus-baumannii complex is an ongoing problem. In fact, the US military health care system has experienced an increased rate of multidrug-resistant Acinetobacter calcoaceticus-baumannii complex infections in military personnel injured in Iraq and Afghanistan. A recent retrospective cohort study found multidrug-resistant Acinetobacter calcoaceticus-baumannii complex to be a frequent cause of infection in burn patients. However infection was not found to independently affect mortality in this population (1). In contrast, bacteremia with K. pneumoniae has been shown to be an independent predictor of mortality in burn patients (46). Yeasts, such as Candida species, and filamentous fungi, such as Aspergillus species, are an increasing cause of burn wound colonization and infection since the introduction of topical antimicrobial agents (18,30).
The filamentous fungi are much more likely to cause invasive disease then the Candida species which are frequently agents of colonization rather then invasion (9, 27, 40, 41, 49). The filamentous fungi commonly associated with burn wound sepsis include Aspergillus sp., Fusarium sp., and members of the Mucorales order of the Zygomycetes (7). There have also been case reports of invasive wound infection due to a variety of dimatiaceous fungi such as Curvularia sp. (22). Unfortunately, fungal infections prove difficult to accurately diagnose as discerning colonization from infection is challenging. A recent retrospective review found that a positive culture of mold, such as Aspergillus, increased the odds ratio of death nearly 12 fold. In contrast, Candida was the most frequently isolated organism but had the lowest associated mortality (4).
Viral infection of burn wounds is rarely reported but does occur. Members of the herpes virus family, including herpes simplex virus (HSV) and varicella zoster virus (VZV), are the most common culprits (41, 52). Cutaneous disease typically occurs in healing partial thickness burns and donor sites.
Pneumonia
The widespread use of topical antimicrobials and early excision and coverage has resulted in a decrease in the frequency of burn wound infection and pneumonia is now an increasing cause of infection in burn patients (40, 41). TheUnited States Army Institute of Research (USAISR) Burn Center identified pneumonia in 169 (17%) of the 998 burn patients admitted over a five year period from 1983-1987. Pneumonia was reported as the cause of death in 83 (50%) of the 166 fatally burned patients over the 5 year period of study (41). Several investigators have reported that the presence of inhalation injury greatly increases the risk of pneumonia as much as two-fold (15, 17, 44, 45). The causative organisms vary between institutions and within individual institutions over time. A comprehensive study of the microbial epidemiology of burn associated pneumonias has not been done. In general, the causative organisms of pneumonia in burn patients appears to be similar to that in other critically ill patients with hospital acquired pneumonia (2). The gram positive agents that have been reported include Streptococcus pneumoniae, methicillin sensitive S. aureus (MSSA) and methicillin resistant S. aureus(MRSA) (15, 41). The gram negative organisms that have been implicated include K. pneumoniae, Haemophilus influenzae, Enterobacter spp., P. aeruginosa, Serretia marcescens, E. coli and Acinetobacter calcoaceticus-baumannii complex (15, 41).
Purulent tracheobronchitis, defined as fever and increased sputum without CXR findings, is frequently encountered in burn patients. It may also be identified as purulent discharge coating the trachea during bronchoscopy. It is typically caused by the same agents responsible for hospital associated pneumonia. The effect of tracheobronchitis on mortality is unclear though there is evidence to suggest that its presence prolongs duration of mechanical ventilation and that antibiotic therapy may mitigate this effect (37).
Blood Stream Infection
Blood stream infection in burn patients may occur as a result of burn wound infection, the use of invasive devices such as central venous catheters, and translocation of gastrointestinal flora. The etiologic agents of burn wound infection have already been discussed. All of these agents pose some risk for blood stream infection though more invasive pathogens such as S. aureus, P. aerugenosa, K. pneumoniae, and Acinetobacter calcoaceticus-baumannii complex are the organisms most commonly associated with bacteremia in burn patients (46). Blood stream infection is a well recognized complication of central venous catheters use. However, data suggests that patients with burn injury are at a much higher risk for central venous catheters colonization and central venous catheters related blood stream infection. There is evidence to suggest that placement of the central venous catheters adjacent to burned tissue increase the risk of catheter colonization and blood stream infection (12, 43, 55). The role of translocation of gastrointestinal flora as a cause of blood stream infection has been evaluated in a variety of critically ill patient populations with varying conclusions as to its significance. With regard to the burn patient, there is evidence that the splanchnic vasoconstriction associated with major burns results in mesenteric ischemia and disruption of the gastrointestinal mucosa thus allowing translocation of resident microflora resulting in bacteremia (29). This mechanism has been clearly demonstrated in animal models but its role in human infection remains inconclusive.
Differential Diagnosis
The differential diagnosis of fever in the burn patient includes both infectious and non-infectious causes (Table 2). Fever, often lasting weeks in duration, occurs as a result of the burn injury itself but other diagnoses must be entertained. The most common infectious etiologies of fever include burn wound infection, pneumonia, and bacteremia. Other considerations include those infections associated with critical illness in general such as urinary tract infections due to use of indwelling catheters, sinusitis in patients with nasogastric tubes and Clostridium difficile colitis in patients receiving antibiotic therapy (48). Non-infectious causes include stroke, myocardial infarction, adrenal insufficiency, acalculous cholecystitis, deep venous thrombosis, pulomonary embolism, hemorrhage (CNS, retroperitoneal, gastrointestinal), drug reactions and transfusion reactions (48, 50).
Clinical Manifestation of Infection
Infection can be difficult to diagnose in any critically ill patient and burn patients are no exception. The primary challenge is in differentiating changes in clinical status as a result of infection from those resulting from the burn injury. The ABA has released a variety of criteria to aid the clinician when interpreting clinical findings in these patients (21). The criteria include findings such as fever and tachycardia but the thresholds are higher then those included in standard definitions of sepsis. The presence of hyperglycemia and intolerance to enteral feedings are also included as clinical markers of sepsis.
The ABA has also recently addressed the classification of burn wound infection and have categorized the spectrum of infection as follows 1) colonization 2) wound infection 3) invasive wound infection 4) necrotizing infection/fasciitisand 5) cellulitis (21). These criteria rely on pathologic characterizations of bacterial load in addition to the clinical findings. A summary of clinical signs associated with burn wound infection in general are listed in Table 3.
Colonization refers to the presence of low concentrations of bacteria in eschar or on the surface of the wound without invasion. It is identified when pathologic examination of wound biopsy specimens reveals <105 organisms/gram of tissue. There are no significant clinical manifestations of burn wound colonization. Wound infection is of much greater concern. It is associated with a higher concentration of organisms then colonization (>105 organisms/gram of tissue). In addition to a higher microbial load, the organisms are located within the wound rather then simply within the eschar or on the wound surface. The most common clinical manifestation of wound infection is a purulent exudate (13). Wound infection and invasive wound infection are defined by the same pathologic criteria (>105 organisms/gram of tissue), however, invasive wound infection is more common in un-excised burn wounds, has more significant local manifestations and is more commonly associated with blood stream infection and sepsis. Invasive infection typically manifests as purulent separation of the eschar in unexcised wounds. It may also present with a rapid change in the appearance of the eschar such as the development of brown, black or violacious areas of discoloration (13, 28). Invasive infection is less common in excised and grafted wounds but when it does occur, it typically manifests as the formation of focal necrosis or neo-eschar on the wound surface (28). Extension of the infection with involvement of unburned skin or grafted tissue may also occur (13, 28). Necrotizing infection/fasciitis refers to the extension of an invasive infection into subcutaneous structures such as muscle and bone. Cellulitis is defined as erythema, warmth and tenderness of the tissue surrounding the wound (21). It may or may not be associated with invasive wound infection and sepsis.
An additional clinical manifestation that warrants mention is burn wound impetigo. Impetigo is classically associated with S. aureus infection. It manifests clinically as loss of epithelium from a previously grafted or healed burn. It may or may not be associated with systemic signs of infection (11, 13, 28). The clinical findings suggestive of pneumonia in burn patients are the same as those for other critically ill individuals. The most common manifestations are sepsis (as previously defined for burn patients), a change in sputum and radiologic evidence of a new or evolving infiltrate, consolidation or cavitation (21). Other diagnoses that mimic pneumonia, such as Acute Respiratory Distress Syndrome (ARDS), tracheobronchitis, pulmonary edema and pulmonary contusion should be considered.
Diagnosis
Burn Wound Infection
The most important method of detecting burn wound infection is daily, close inspection of all burn wounds by experienced personnel (42). Several types of infection, including cellulitis, invasive infection, and impetigo can be distinguished by routine examination, and used as an indication to obtain cultures and/or begin empiric antibiotic therapy. A variety of techniques, such as surface swabs, tissue culture and tissue histopathology, are available for the microbial diagnosis of burn wound infection. Of the available methods, wound biopsy with quantitative culture and wound biopsy with histopathology are utilized by many burn units. Superficial wound swabs are misleading as they typically result in identification of colonizing organisms. Therefore, there is no role for superficial swabs in diagnosis of burn wound infection. Tissue histopathology and culture are preferred over simple wound swabs for accurate identification of burn wound infection. The use of burn wound histopathology to detect micro-organisms penetrating beneath burn eschar into viable tissue has long been considered the “gold standard” for diagnosis of invasive burn wound infection/sepsis (16, 42). This method differentiates colonization from invasion based upon the location of the microorganisms within the wound (Table 4) and is the diagnostic modality of choice for most burn centers (16, 42).
For many years, quantitative cultures of burn wound biopsies have been used to diagnosis burn wound infections, with cultures growing ≥ 105 organisms/gram of tissue considered “positive”. Quantitative cultures of wound biopsies are more specific than swab cultures, but have a number of limitations. Among them is the finding that clinically septic patients often have far higher density of bacterial counts, sometimes as much as 1011 organisms/gram of tissue (14). Therefore the current “positive” culture threshold of ≥ 105 organisms/gram of tissue may not be precise enough to distinguish limited from invasive infection. In addition, quantitative cultures are costly and time-consuming, with low rates of positivity in many patients. Because such cultures represent a random “sample” from a single site, they may miss significant infection in adjacent wounds. Both false-positive and false-negative results are possible, further limiting their correlation with systemic infection (20,31). The primary benefit of wound cultures is in detecting and identifying the antibiotic susceptibilities of predominant wound microflora when used in conjunction with histopathology.
Pneumonia
The microbiologic diagnosis of pneumonia should be made in conjunction with appropriate clinical findings of sepsis, a change in sputum and/or a new or evolving abnormality on CXR. There are a variety of methods for obtaining respiratory material for microbiologic diagnosis to include sputum culture, tracheal aspirate, bronchoalveolar lavage (BAL) and bronchoscopy with protected bronchial brush (PBB). The method chosen will vary with the clinical status of the patient and the expertise of treating physicians. Sputum culture results are reported qualitatively or semi-quantitatively (i.e. light, moderate or heavy growth) (2). This method often identifies one or multiple organisms and it may be difficult to differentiate between colonizing organisms and true pathogens. The end effect is often over-treatment. The culture results for samples collected through tracheal aspirates, BAL and PBB are typically reported in a quantitative fashion. Each method has a different threshold to distinguish colonization from infection. The commonly used thresholds for defining infection are as follows 1) Tracheal aspirate: ≥105 organisms 2) BAL: ≥104 organisms and 3) PBB: ≥103 organisms (2, 21). It should be noted that these thresholds do not take prior antibiotic therapy into account and may need to be lowered if a recent change in antibiotic treatment has occurred. In addition to augmenting clinical findings of pneumonia, cultures enable identification of drug resistance and may result in a broadening or narrowing of antibiotic therapy.
Blood Stream Infection
A diagnosis of blood stream infection is made when a recognized pathogen (defined as a microorganism that is not considered a common skin commensal) is cultured from one or more blood cultures or when a microbe recognized as a common skin contaminant (coagulase negative staphylococci, Propionibacterium spp.) is isolated from two or more blood cultures drawn on separate occasions with associated signs of sepsis (10, 21). Blood stream infection may occur in the absence of an obvious source in which case it is classified as a primary blood stream infection. Secondary blood stream infection occurs as a result of infection with the same organism at another site (burn wound infection or pneumonia). Patients with indwelling intravascular devices are at risk for central venous catheter related blood stream infection. The distinction is important as it affects the management of the patient and impacts the likelihood of additional studies being performed (i.e. echocardiogram for primary blood stream infection). It should be noted that burn patients are at a high risk for bacteremia (35). Transient bacteremia has been detected following wound manipulation during routine surveillance programs in burn. However episodes of transient bacteremia in the absence of sepsis have not been found to be clinically relevant and initiation of antibiotic therapy for these episodes has no effect on outcomes (57). Therefore, blood cultures are clearly indicated in patients with sepsis but routine surveillance cultures are not recommended.
Empiric and Targeted Antibiotic Therapy
Topical Therapy
Empiric therapy is often necessary in the setting of suspected infection. In the case of burn patients, this therapy may be topical and/or systemic. It is debatable if topical therapy should be considered empiric or preventative as it is indicated for all burn wounds independent of the concern for active infection. The widespread, systematic use of topical antimicrobials has been associated with a significant decline in the incidence of burn wound infection. The most commonly used topical agents are mafenide acetate, silver sulfadiazine, silver nitrate solution and silver-impregnated dressings.
Mafenide acetate (Sulfamylon®) is available as an 11% water-soluble cream that rapidly penetrates full thickness eschar and exerts a broad antibacterial effect (23). In-vitro and animal studies have demonstrated mafenide acetate to have efficacy against Staphylococcus and Pseudomonas species (59). There are reports of resistant strains of Providencia and Enterobacter from USAISR burn unit in the late 1960’s but none of the nearly 8,500 strains of P. aeruginosa isolated from USAISR burn patients during the period 1967-1992 were resistant to clinically relevant concentrations of the drug (11). There are some shortcomings to mafenide acetate. The primary hole in coverage is its lack of efficacy against fungal pathogens. It is also painful on application, a consequence of its otherwise desirable ability to penetrate eschar and reach viable tissue. In addition, the drug and its primary metabolite (p-carboxybenzenesulfonamide) are inhibitors of carbonic anhydrase and metabolic acidosis has been reported in patients with extensive burns treated twice daily (60). This may pose a problem given that concentrations of the drug in eschar drop below therapeutic levels approximately 10 hours after application, necessitating twice daily dosing unless a second agent is also used (23). One common practice is to apply mafenide acetate in the morning and silver sulfadiazine 12 hours later in order to realize the benefits of both drugs while limiting the toxicities (11).
Silver sulfadiazine (Silvadene®, Thermazine®, Flamazine®, SSD®, Burnazine®) is available as a 1% water soluble cream. Much like mafenide acetate, silver sulfadiazine exhibits activity against gram negative and gram positive organisms; however, unlike mafenide, it has poor eschar penetration (19, 24). The advantages of silver sulfadiazine are that it is relatively painless on application and it has some activity against Candida species, but not against filamentous fungi such as Aspergillus. Occasionally, a transient decrease in leukocyte count has been observed with initiation of therapy. This effect is likely due to suppression of granulocyte-macrophage progenitor cells in the marrow (56). This reaction typically resolves even when the agent is continued and it rarely necessitates discontinuation of therapy (56).
Silver nitrate (AgNO3) solution is used as a 0.5% aqueous solution, a concentration at which it is not toxic to regenerating epithelium as higher concentrations used in the past have been (24, 34). The process of application requires that burn wounds be dressed with multiple, thick layers of coarse mesh gauze, to which the silver nitrate solution is frequently reapplied in order to keep the gauze continuously moist (11). Much like silver sulfadiazine, it exhibits activity against gram positive bacteria, gram negative bacteria and Candida. It lacks activity against the filamentous fungi. The major deficiencies of silver nitrate solution are that it has poor penetration of eschar, requires the use of occlusive dressings, and turns black upon contact with tissues (24). In addition, the dressings must be changed twice daily to prevent buildup of tissue-toxic levels of the silver nitrate. Another drawback to this drug is the depletion of cations due to leeching across the open wound into the hypotonic solution. This phenomenon may result in hyponatremia, hypocalcemia, hypokalemia, and hypomagnesemia; therefore, close monitoring of electrolytes is necessary (34). A variety of dressings impregnated with elemental silver have been approved by the FDA as topical therapy for burns. Numerous formulations of these dressings are now available, but it is unknown if they are equivalent in silver delivery and antimicrobial efficacy. In general, the silver dressings are effective against gram positive and gram negative bacteria. There is limited in-vitro data to suggest these dressings have activity against Candida spp. and some molds though further studies are required (32). Examples of available silver dressings include Silverlon® (Argentum LLC, Willowbrook, Il) and Acticoat® (Smith and Nephew, Hull, United Kingdom). Both Acticoat® and Silverlon® are approved for use in superficial and partial thickness burns and can be left in place for several days. This offers advantages for the treatment of wounds sufficiently small that outpatient or ward care are reasonable options. The spectrum and side effects for each of the topical agents is summarized in Table 5.
Systemic Therapy
In addition to topical therapy for burn wound infection, patients with pneumonia, burn wound infection and/or evidence of sepsis require systemic antibiotic therapy. Decisions regarding empiric antibiotic therapy should be made with knowledge of resistance patterns reflected in the antibiogram of an individual facility or burn unit. That being said, most patients will require broad coverage for gram positive and gram negative organisms to include P. aerugenosa and in some cases, MRSA. In most situations a regimen consisting of vancomycin plus an anti-pseudomonal antimicrobial plus either a fluoroquinolone or aminoglycoside is indicated up front. In facilities with a high incidence of extended beta-lactamase producing organisms (ESBL), an anti-pseudomonal carbapenem is the broad spectrum agent of choice. It is imperative that this broad, empiric antibiotic therapy be coupled with a thorough search for the microbial etiology of the infection with subsequent tailoring of regimen once the culprit is identified.
Targeted antibacterial therapy is superior to empiric therapy in that it enables treatment of the infection with limitation of the side effects posed by the administration of multiple antimicrobials. Directed therapy also limits the pressures that foster antibiotic resistance. In addition to the sensitivities of the offending organism, antibiotic selection will be affected by patient co-morbidities such as allergies and the presence of renal failure. Other factors to consider are the presence of a drug of choice for specific infections such as oxacillin or nafcillin for MSSA and a carbapenem for ESBL producing gram negatives. Recommendations specific for burn wound infection, pneumonia and blood stream infection in burn patients have not been established. However, there are data from the general critical care and infectious disease literature that can be used for guidance.
Empiric therapy of fungal infection has become more complicated as many new agents with varying side effects and spectra of activity have become available. Invasive burn wound infection due to Candida spp. is uncommon; therefore, therapy should ideally be directed by results of wound histopathology. With regard to candidemia, treatment should be initiated based on the results of blood cultures. If empiric therapy is administered, it should be guided by the incidence of C. albicans versus non-albicans infections in a given institution. The most commonly used treatment options for candidemia include fluconazole and the echinocandins. Fluconazole has activity against many species of Candida though higher doses of 800 mg/day are required for C. glabrata infections due to the intermediate resistance commonly exhibited by this organism. Fluconazole is ineffective against C. krusei, therefore, an echinocandin is a reasonable agent for infections due to this organism. Amphotericin B products are an option for severe candidal infections; however the associated toxicities often limit its use. Like the echinocandins and Amphotericin B products, voriconazole has broad activity against Candida species, however it is preferable that this agent be reserved for use in infections due to filamentous fungi such as Aspergillus.
With regard to invasive burn wound infection, antifungals should be thought of as an adjunct to aggressive surgical debridement. Broad spectrum antifungal therapy with voriconazole or an amphotericin B formulation is indicated pending definitive identification as most invasive fungal burn wound infection are due to filamentous fungi such as Aspergillus spp. and the Zygomycetes. It should be noted that voriconazole exhibits excellent activity against Aspergillus spp. but has no activity against members of the Zygomycetes such as Rhizopus spp. and Mucor spp. Amphotericin B products exhibit activity against most species of Aspergillus, the exception being A. terreus, as well as the Zygomycetes. Posaconazole, a newer agent, exhibits activity against both Aspergillus spp. and the Zygomycetes, however it is available only in an oral formulation which limits its use in critically ill patients.
Non-Antibiotic Interventions
Aggressive surgical care of the burn wound is the most important intervention for control of burn wound infection. Excision and grafting is clearly indicated for deep partial thickness burns and for full thickness burns. Early excision of burned tissue and coverage with skin grafts or skin substitutes has been associated with a decrease in mortality in several studies (38). The beneficial effect on mortality is likely multi-factorial, with a decreased incidence of wound infection and the removal of devitalized tissue as a stimulus for the inflammatory process both likely playing a role. The definition of “early” has not been definitively established. Studies have variably defined early excision as that performed either upon admission or up to 5 days after injury (38). The options for coverage of debrided wounds are varied. Full or partial thickness autograft is the treatment of choice for definitive coverage, but its use is limited by the availability of donor sites. If sufficient autograft is not available, temporary biological and synthetic coverings may be utilized to cover the wounds until donor sites have healed and are ready for re-harvest. The available temporary, biological dressings consist of allografts (cadaveric skin or amnionic membrane) and xenografts (typically porcine skin) (25). There are several brands of synthetic coverings available, such as Biobrane® and Integra®. These dressings act as a wound barrier and prevent evaporative losses but have no intrinsic antimicrobial properties.
Prevention
The prevention of infection within a burn unit relies heavily on the use of proper infection control measures. There are currently no infection control guidelines specific to the burn unit but general infection control recommendations offer some guidance (2, 53, 58). Both exogenous and endogenous organisms are implicated in burn wound infection, pneumonia and bacteremia. Exogenous organisms are those acquired from the hospital environment such as medical equipment and the hands of health care workers. Hand hygiene compliance and cohorting of patients with multidrug resistant organisms has demonstrated a decrease in infections in some burn units (54). With regard to burn wound infection, early colonization with endogenous organisms occurs within the first 24-48 hours after injury. The practice of early excision and grafting coupled with topical antimicrobials is the best defense against burn wound infection. Pneumonia in burn patients has also been commonly associated with infection due to endogenous flora. Modifiable factors that have been found to decrease the risk of pneumonia include maintaining head of bed elevation > 450, continuous sub-glottic suctioning of secretions and the use of daily interruptions in sedation in order to avoid prolonged, heavy sedation which may result in depression of cough reflex (2, 58). The factors that have been reported to decrease the risk of blood stream infection include tight control of blood glucose in the range of 80-100 mg/dl as well as the use of enteral nutrition over parenteral nutrition in order to decrease the risk of catheter related blood stream infection and to prevent villous atrophy of the intestinal mucosa that may predispose to bacterial translocations (58). The role of prophylactic antibiotics for burn patients undergoing dressing changes has been evaluated and is of no benefit. In addition, studies examining the use of pre-debridement antibiotic prophylaxis of burns <40% TBSA show no clear benefit (39). There are limited data for the role of peri-operative prophylaxis for debridement of burns >40% TBSA, therefore it can be considered for these patients pending further data. The role for interventions such as selective digestive tract decontamination, oral antiseptic washes and enteral feeding acidification remain unclear.
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Tables
Table 1: American Burn Association Sepsis Criteria (21)
Sepsis is present if a documented infection is identified by culture, pathology or a clinical response to antibiotics and three of the following criteria are met.
|
|---|
I. Temperature >39° or < 36.5°C |
II. Progressive tachycardia ▪Adults >110 beats per minute ▪Children > 2 SD above age specific norms (85% age-adjusted heart rate) |
III. Progressive tachypnea ▪Adults > 25 breaths per minute if not ventilated or minute ventilation >12 1/min if ventilated ▪Children > 2 SD above age specific norms (85% age-adjusted respiratory rate) |
IV. Thrombocytopenia (Only applicable > 3 days post initial resuscitation) ▪Adults <100,000/mcl ▪Children > 2SD below age specific norms |
V. Hyperglycemia (Only applicable to patients without a prior history of diabetes) ▪Untreated plasma glucose > 200 mg/dL Or ▪Insulin resistance (>25% increase in insulin requirement over 24 hours) |
VI. Inability to continue enteral feedings >24 hours ▪Abdominal distension Or ▪Residual two times feeding rate for adults or >150 ml/hr in children Or ▪Uncontrolled diarrhea (>2500 ml/day for adults or >400 ml/day for children) |
SD = standard deviations
Table 2: Differential Diagnosis of Fever in the Burn Patient (48, 50)
| Infectious | Non-infections |
|---|---|
| Burn wound infection | Burn wound |
| Bacteremia/Fungemia | Thrombosis (DVT, PE)* |
| Pneumonia | Hemorrhage |
| Tracheobronchitis | Stroke |
| Sinusitis | Myocardial infarction |
| Clostridium difficle colitis | Acalculous colecystitis |
| Urinary tract infection | Pancreatitis |
| Surgical site infection | Adrenal insufficiency |
| Drug fever | |
| Transfusion reaction |
*DVT- deep venous thrombosis; PE- pulmonary embolism
Table 3: Local Signs of Burn Wound Infection (11, 13, 28)
● Purulent exudate from a previously excised wound bed |
● Focal necrosis or formation of neo-eschar in a previously excised wound |
● Early separation of eschar from an unexcised wound |
● Focal brown, black or violacious discoloration of eschar |
● Erythema, warmth or tenderness of surrounding tissue* |
● Loss of epithelium from previously grafted or healed burns╪ |
● Vesicular lesions in healed or healing partial thickness burns◊ |
*Characteristic of cellulitis
╪Characteristic of impetigo
◊ Characteristic of Herpes Simplex Virus infection
Table 4: Histopathologic Classification of Burn Wound Infection (11, 42)
Stage |
Grade |
|---|---|
I. |
A. Microbes present on eschar surface |
B. Microbes present throughout eschar |
|
C. Microbes multiplying beneath eschar |
|
II. |
A. Foci of microbes in viable tissue immediately beneath eschar |
B. Multifocal or diffuse penetration of microbes into viable tissue |
|
C. Microbes present in unburned blood vessels and lymphatics |
Table 5: Application of Topical Agents (11, 23, 32)
Agent |
Penetration |
Spectrum |
Side Effects |
|---|---|---|---|
Mafenide Acetate |
Penetrates eschar |
Gram positive Gram negative |
Painful on application Metabolic acidosis |
Poor eschar penetration |
Gram positive Gram negative Candida spp. |
||
Silver Nitrate |
Poor eschar penetration |
Gram positive Gram negative Candida spp. |
Discolors wound bed Electrolyte changes |
Acticoat® or Silverlon® |
Poor eschar penetration |
Gram positive Gram negative Candida spp.* |
Discolors wound |
*Data are limited