According to the American Burn Association, approximately 486,000 persons were treated for burns in 2011 in the United States; of these, approximately 40,000 were hospitalized and approximately 3240 died of the burn injury. Most of the deaths were related to residential fires, and about 75% of the deaths occurred before arrival at the hospital. For those who are hospitalized, mortality rate peaks 20 days after hospital admission. Improvement in the rate of burn-associated mortality is a direct result of advancement in burn care, comprising developments in fluid resuscitation, wound care, early excision and grafting, nutritional support, infection control, and antimicrobial therapy. The mortality rates and lengths of stay of children with burn injury have been reduced greatly in the past several decades. In the 1960s, the likelihood of survival was only 50% for pediatric patients with burns covering 35% to 44% of the total body surface area (TBSA), and few children with burns covering more than 45% of TBSA survived. The average length of stay was 103 days. In 2011, the LA 50 (lethal burn size for 50% of patients) for children younger than 16 years exceeded 90% of TBSA. The overall mortality rate for children is less than 1%, which is much lower than that of adults, who have mortality rates in the range of 2% to 26%. At the Shriners Hospital for Children–Galveston, sepsis was found to be the leading cause of death and accounted for 47% of deaths.
Burn Wound
Burn Wound Depth
Burn wounds are categorized by their depth ( Fig. 76.1 ). Accurate assessment of the depth of burn wounds is important in planning the early definitive care of an individual patient. However, the majority of burn wounds are evaluated by clinical examination only. In this respect, laser Doppler imaging is an important advance in noninvasive techniques for predicting burn wound depth.
Superficial-thickness burns consist of epidermal damage only. These wounds are painful and erythematous as a result of local vasodilation. They heal spontaneously, usually without forming scars, within 7 days.
Partial-thickness burns involve superficial portions of the dermis. These wounds are painful and often result in formation of blisters. Healing occurs through epithelial migration from the wound edges, hair follicles, and sebaceous glands. Relatively little scarring occurs, and reepithelialization occurs within 2 weeks. Deep partial-thickness burns are much more serious. The majority of the dermis is destroyed, leaving the bases of the epidermal appendages spared. The nerve endings also are destroyed, rendering the wound insensate. Blisters usually are not present, owing to the thicker formation of eschar. These wounds are treated as full-thickness injuries. Reepithelialization is tenuous and slow. The protracted inflammatory phase often results in excessive deposition of collagen and extensive scarring.
Full-thickness burns involve the entire epidermis, dermis, and the deeper subcutaneous tissues. Healing occurs by contraction and reepithelialization from the edges of the wound. These wounds are insensate and without blistering. Infants and young children have a much thinner dermal layer to their skin resulting in increased propensity for deeper burn injury. Treatment requires excision and skin grafting.
Full-thickness burns can extend into the deep tissue, which includes muscle, bone, and viscera. Treatment is debridement and possible amputation. Closure of these wounds may vary from primary closure after amputation to skin grafting and possibly flap reconstruction.
Cytologic Findings
The effects of extreme heat on the skin lead to cellular and subcellular impairment. The determining factors of how severe a burn will be are the temperature, the length of exposure, and the actual burning agent. Moritz and Henrique showed that the skin is able to withstand temperatures up to 40°C (104°F) for relatively long periods of time before an injury becomes apparent. Increase in temperature leads to cell membrane dysfunction as ion channels are disrupted, resulting in sodium and water intake. As temperatures exceed 45°C (113°F), protein denaturation supersedes the cell’s reparative capabilities, and oxygen radicals are liberated. Plasma membrane necrosis has been observed in cells exposed to 45°C for 1 hour. Other cytologic findings in thermal injury include the redistribution of solid and fluid components of the cell nuclei. Imbibition of fluid results in nuclear swelling, rupture of membranes, and pyknosis. As denaturation proceeds, vital cellular metabolic processes are injured. If enzyme activity is decreased to less than 50% of its normal level, cell death occurs. In lesser degrees of enzyme impairment, cell recovery may be possible.
Local Tissue Changes
Local burn injury is classically described by Jackson in three concentric zones. As temperature increases, protein denaturation results in coagulation. The protein architecture is destroyed and new aberrant macromolecules are formed. The central area of a burn wound is that which is in direct contact with the source of heat. Cell necrosis is complete and is called the zone of coagulation. Cellular recovery is impossible, and the severity of injury decreases from the surface to the deeper levels. This zone is called the burn eschar. At the peripheral margins of the zone of coagulation, a less injured zone is present. The cells in this zone of stasis show direct injury from the heat, but the damage is not lethal. However, blood flow becomes progressively impaired to this area. Ischemia to the already compromised cells may lead to necrosis and conversion to dead eschar. Circulatory impairment occurs via adherence of neutrophils to the vessel wall, deposition of fibrin, formation of platelet microthrombus, vasoconstriction, and endothelial swelling. Heat-compromised erythrocytes lose their ability to deform, and their passage through microvessels is impeded. The circulatory embarrassment may be delayed for up to 24 hours, and the ischemia may progress for up to 48 hours after the burn has occurred. If stasis conditions are minimal, the injury may be halted and cell recovery may occur within 1 week. However, this tissue is fragile and further insults such as infection, hypovolemia, pressure, and overresuscitation can lead to further necrosis. Finally, the zone of hyperemia lies peripheral to the zone of stasis. This zone sustains minimal injury and often recovers within 7 to 10 days. Notable vasodilation is caused by potent vasoactive mediators secondary to the inflammatory response. Complete recovery is expected in this zone, barring further trauma or infection.
Burn Inflammation
Many of the just mentioned processes are either part of or result from the inflammatory process. Cellular infiltration, initiated by local inflammatory mediators such as prostanoids and leukotrienes, as well as proinflammatory cytokines from the burn wound, begins with the arrival of neutrophils at 4 to 5 days after the burn, followed by macrophages. The neutrophils further mediate damage by releasing oxygen free radicals. Reestablishment of blood flow in the zone of stasis is yet another setting in which oxygen free radicals are produced, leading to further injury. This phenomenon of ischemia-reperfusion injury occurs as oxygen is restored to the tissues. Inflammation becomes prominent at 7 to 10 days. Consequently blood flow is maximal at this stage, creating a troublesome and hazardous setting for surgical excision of the eschar. Along with local inflammatory responses, several systemic responses occur with burns of more than 15% of the TBSA.
Inhalation Injury
Burn victims, especially those trapped in enclosed areas, injure the respiratory tract on inhalation of toxic gases from surrounding burning materials. An actual thermal airway injury is quite rare. The upper airway is rather effective in cooling and warming inspired air. Also, air has a very low heat capacity. To cause a direct injury to the airway, the flames must come into direct contact with them. Injury to the oropharynx after inhalation of toxic gases resembles thermal injury elsewhere in the body. Protein denaturation, release of inflammatory mediators, and increased cellular and microvascular permeability all occur, leading to airway edema and consequent obstruction of the airway.
The chemical injury from inhalation of toxic gases can damage the tracheobronchial tree. First, separation of ciliated epithelial cells from the basement membrane occurs. Next, the circulation of blood to the lung, as well as to the bronchial tree, is increased owing to vasodilation. Shortly thereafter, edema is evident. The inflammatory phase is followed by an exudative phase. Furthermore the protein component of this fluid is composed of lung lymph and induces bronchoconstriction. As postburn time increases, fibrin casts are formed from the exudates, resulting in obstruction of the airway. As the epithelium sloughs and formation of fibrin casts increases, susceptibility to infection also increases. Pneumonia leading to sepsis and death are well-known sequelae at this stage. Finally formation of pseudomembranes proceeds and then squamous metaplasia follows. Healing may take weeks to initiate, and permanent damage to the airway (e.g., stenosis and formation of tracheal granulomas) may occur.
Inflammatory and Immune Responses in Burns
Intact human skin is vital for preservation of the host’s protection against infection. A combination of impaired local and systemic host defenses and loss of the skin barrier are major factors responsible for the increased susceptibility to infections in patients with burns. The major elements initially contributing to the inflammatory response that occurs after burns are incurred include the plasma proteins, mast cells, tissue macrophages, and systemically recruited neutrophils and monocytes.
Alterations in the host defenses include induction of local and systemic cytokine synthesis, decreased immunoglobulin levels, changes in the concentration and activity of both the classical and alternative complement pathways, reduced levels of circulating plasma fibronectin, depressed serum opsonic activity, and impairment of the macrophages, lymphocytes, neutrophils, and the reticuloendothelial system. However, many mechanisms of immune alterations remain unknown; for example, an association of the volume of blood transfusions with increased mortality rates and infectious episodes in patients with major burns was observed in two reports. The immunologic status of the burn patient has a measurable impact on survival, death, and major morbidity.
The Cytokine Response
After burn injury occurs, numerous cytokines are induced rapidly. Many cytokines correlate with the severity of the burn injury and the prognosis. Studies at Shriners Hospital for Children–Galveston have shown a specific pattern of systemic cytokine responses in children with thermal injury. Compared with unburned healthy children, children with burns covering more than 40% of TBSA had significant increases in serum levels of 15 cytokines and immunoregulatory molecules during the first week after incurring the thermal injury: interleukin-1β (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17, interferon-γ (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and granulocyte colony-stimulating factor (G-CSF). The amount of granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly increased during the second week after burn occurred. Within 5 weeks, the serum concentrations of most cytokines decreased, approaching normal levels. In another study of children, serum IL-6, IL-8, IL-10, IL-12p70, IL-13, IFN-γ, tumor necrosis factor-α (TNF-α), MIP-1β, MCP-1, G-CSF, and GM-CSF values were significantly increased in large burns. In general, there is a clear increase in these cytokines when the affected TBSA is greater than 60% when compared with burns affecting a lesser TBSA.
A recent multicenter study specifically looked at the predictive value of IL-8 for sepsis and infection following burn injury. This study enrolled 468 pediatric burn patients with burns of greater than 30% TBSA and used IL-8 levels to stratify patients into IL-8 low and high groups. These patients were monitored for IL-8 levels for the first 60 days after injury. Based on the results, IL-8 may be a useful biomarker in pediatric burn patients for monitoring multiorgan failure, infections, sepsis, and mortality. Another study also reported that pediatric patients with multiorgan failure had significant increases in serum IL-6, MCP-1, and TNF-α, but these were not predictive of outcome. TNF-α may be the most important cytokine during acute inflammatory injury of burns because it induces production of C-reactive protein (CRP) and IL-6; migration of and phagocytosis by neutrophils and macrophages; hormone regulatory processes, particularly hypothalamic thermoregulation; and insulin hypersensitivity.
In children with inhalation injury, the serum cytokine studies at enrollment showed significant reduction in level of IL-7 and elevation of IL-12p70 compared with children without inhalation injury. However, 5 to 7 days later, the levels were comparable. Host genetic factors also may affect the cytokine response in patients with burns. For example, single nucleotide polymorphisms for TNF-α (−308G), Toll-like receptor 4 (+896G), IL-6 (−174C), and CD14 (−159C) were significantly associated with an increased risk for severe sepsis after burns.
In another study, children with IL-10 (−1082GG) genotype, which is associated with high production of IL-10, were found to have an increased risk for sepsis. IL-10 has also been shown to be upregulated in the sera of pediatric burn patients. Furthermore IL-10 has recently been linked to inhibition of IL-17–producing CD4 + T cells (T H 17 cells), leading to a decreased response to Candida albicans infection.
Neutrophils
Thermal injury induces neutropenia and myeloid maturation arrest despite elevated G-CSF levels. The degree of neutropenia correlates with the reduction in bone marrow G-CSF receptor expression. The neutrophils of patients with burns also are functionally altered: the expression of the Fc receptor is decreased, and intracellular killing capacity is depressed (this is a differential suppression, more for some organisms than others) and is accompanied by a brief increase in neutrophil respiratory burst response. Failure of initial alkalization of the phagolysosome and alteration of subsequent kinetics of acidification also occur. This depression of oxygen-independent bactericidal mechanism may impair the capacity of the neutrophil for intracellular killing after a thermal injury occurs. Expression of CD16 (Fc receptor [FcR], Fc immunoglobulin G [IgG] receptor) and CD11 (adhesion molecule) on neutrophils is impaired after a major injury occurs; this reduction appears to be related directly to the appearance of bacteremia or pneumonia. These changes in expression of adhesion molecules, which is closely related to chemotaxis, may play a part in the failure of delivery of neutrophils in adequate numbers to the local site of a burn. Furthermore a defect is present in actin polymerization in the neutrophils of patients with burns; as a basic mechanism of chemotaxis, it also may contribute to a failure of motility. Neutrophil directional migration has also been shown to be impaired in burn patients compared to healthy individuals. The ability of glutamine to increase the bactericidal function of neutrophils against Staphylococcus aureus has also been reported in neutrophils isolated from pediatric burn patients.
Generation of leukotrienes from the neutrophils of severely burned patients also is impaired and appears to be based on the availability, or lack of availability, of the metabolizable substrate-free arachidonic acid. Because leukotriene B also is a potent neutrophil chemotactic agent, this impairment may further contribute to the failure of neutrophil function.
Complements
The fluid of the burn blister shows much lower opsonic activity for bacteria such as Pseudomonas aeruginosa than the patient’s own serum. A mild impairment of production of C3 and release by macrophages of burn patients in vitro also occurs. Systemically both the classical and the alternative pathways are depleted, but the alternative pathway is more profoundly perturbed. After the development of bacteremia, additional complement activation and depletion occur.
Macrophages
Suppression of the ability of the reticuloendothelial system to take up particulate material was among the original observations of burn immunology made in the 1960s. More recent reports, however, have described the demonstration of a differentially increased uptake of colloid in alveolar macrophages compared with other organs, perhaps indicating alveolar macrophage activation. Macrophages and monocytes appear to be activated in a fashion similar to that of lymphocytes after thermal injury occurs. Activation of macrophages, as measured by the serum neopterin level, is increased after thermal injury occurs. This activation is confirmed by increased expression of the monocyte cell surface antigens C3b and iC3b. At the same time, expression of human leukocyte antigen-DR (HLA-DR), HLA-DQ, and HLA-DP by monocytes is reduced, and these class II antigens are obligatory for many cell-mediated immunologic processes, thereby implying that a possible loss of function of monocytes occurs after thermal injury. Production of C3 by macrophages is suppressed in patients with burns, but the synthetic ability for key cytokines such as IL-6 is increased.
Peripheral blood monocytes are superstimulated to produce large amounts of IL-1, leading to exhaustion of the function on monocytes. Reduced production of IL-1 by monocytes was found in patients with complicated organ injury, multiorgan failure, and systemic infection. Peripheral blood monocytes from severely burned patients also fail to produce MIP-1α, which has been shown to play an important role in recruitment and activation of various immune cells during infection. Blood monocytes of patients with burns produce significantly more IL-10 at 7 to 10 days after burn injury, which correlates significantly with subsequent septic events.
T Lymphocytes and Cell-Mediated Immunity
Early studies of T cells in patients with burns showed a variety of changes: impairment in mitogenic and antigenic responsiveness of lymphocytes, suppression of graft-versus-host reactivity related to the size of the burn, suppression of delayed cutaneous sensitivity tests, and diminution in both numbers of peripheral lymphocytes and concentration of thoracic duct lymphocytes. Whether the failure of T-cell functions is due to an intracellular defect related to thermal injury, the result of “overuse,” or indirectly the result of downregulation by the cytokine cascade or other products of the inflammatory reaction remains controversial. A study has shown that severe burn injury could result in activation and maturation of regulatory T cells leading to immunosuppression. The elevation of levels of cytokines produced by regulatory T cells and the activation markers on the surface of these cells correlate with burn size and are higher in those with sepsis than those without. However, among septic patients, the regulatory T-cell parameters in the survival group were markedly lower than those with fatal outcome, suggesting that persistence of a pronounced immunoparalysis induced by regulatory T cells after severe sepsis is associated with poor outcome after burns.
IL-17–producing CD4 + T cells (T H 17 cells) have been shown to have an important role in protection from Candida albicans infection. A recent study looking at the ability of burn patients to generate T H 17 cells in response to C. albicans showed that their generation was impaired in pediatric and adult burn patients, presumably due to T H 17-inhibiting IL-10 produced as a result of burn injury. Since burn patients are quite susceptible to C. albicans infection, lack of T H 17 T-cell generation may be one mechanism by which infection occurs.
Analysis of peripheral blood T cells supports the theory that, rather than an absolute reduction in CD4 and an increase in CD8 cells, a redistribution of lymphocyte traffic may occur. Suppression in the numbers of the total population of lymphocytes is the only consistent overall change. Furthermore not only does lymphocyte traffic between stores of central lymphocytes and the peripheral blood occur after a thermal injury, but the responsiveness of these populations of lymphocytes also varies according to the site; for example, splenic lymphocytes of experimentally burned animals remain most profoundly depressed in response to antigenic stimulation compared with the peripheral blood and other organs. In addition, in peripheral blood, the appearance of “activation” antigens on CD4 and CD8 cells (HLA-DR, IL-2 receptor [IL-2R], and transferrin receptor) is depressed significantly as early as 1 day after burn injury occurs.
Addition of recombinant IL-2 does not appear to reverse the suppression of the appearance of surface markers such as IL-2R in burn patients, although it does not improve the response of natural killer (NK) cells to stimulation. In experimental preparations, at least some of the observed T-cell suppression can be alleviated by early removal of the burn wound, thereby creating one further argument for promptly closing the burn wound.
B Lymphocytes and Humoral Immunity
The function of B cells after the occurrence of a thermal injury is less well documented than is that of macrophages or T cells. The expression of this major histocompatibility complex is impaired and therefore some diminution of B-cell function can be expected as a result of diminished recognition of antigenic presentation. Under the influence of stress-induced corticosteroids, the number of circulating B cells is relatively increased compared with T cells in peripheral blood. Spontaneous cytokine (IL-4 and IL-2)-induced expression of the activation antigen CD23 is reduced significantly during the second to fifth week after burn injury occurs.
If the products of B-cell activation, namely, the immunoglobulins, are measured in vivo, the results are somewhat difficult to interpret because of the increased catabolism of protein and the leakage through the burn wound. Briefly, marked diminution of serum IgG concentration (total and all subclasses) is present; these levels return to normal between 10 and 14 days after the burn injury has occurred. Extremely low levels of IgG on admission (300–400 mg/dL) are predictors of a poor prognosis. One study looking at immunoglobulin levels in pediatric burn patients found that the greatest drops were seen in IgG1 and IgG2 subclasses. Levels of IgM and IgA appear to be relatively unaffected.
Overall the defective production of immunoglobulin after a thermal injury occurs appears to be a factor of macrophage/lymphocyte interaction rather than a failure of intrinsic activity by B cells.
Burn Wound Microbiology
A working knowledge of the common flora of burn wounds is essential to appropriately tailor therapy. Pathogens peculiar to thermal injuries are basically no different from the normal flora of the environment. Table 76.1 shows the types of microorganisms found in various body tissues and secretions as either normal flora or as pathogens. However, the organisms causing infections change over the course of burn wound treatment. Gram-positive organisms prevail in the early postburn period and then are replaced by gram-negative bacteria and fungi. Many of these organisms produce biofilms in burn wounds. The biofilms consist of organisms surrounded by a matrix consisting of various proteins, polymers, complex carbohydrates, and water. Biofilms are associated with development of antibiotic resistance because antibiotics do not penetrate through the matrix in sufficient concentration. Biofilm formation also inhibits effective local immune response as well as wound healing. Using electron microscopy, Kennedy and colleagues showed that in both ulcerated and escharotomy sites, evidence of biofilm was seen as early as 7 days after injury. Formation of biofilm is best prevented by early excision and coverage of the wound with topical antimicrobial agents.
| Organism | Soft Tissue Skin | Upper Respiratory Tract | Lower Respiratory Tract | Endocardial | Gastrointestinal | Urogenital | Bone and Joint |
|---|---|---|---|---|---|---|---|
| Staphylococcus aureus | NF, P | P, NF | P | P | P | NF, P | P |
| Staphylococcus epidermidis | NF, P | NF, P | P | P | P | NF, P | P |
| Other staphylococci | NF | NF, P | P | P | NF, P | NF, P | P |
| Streptococcus pyogenes | P, NF | P, NF | P | P | P | P | P |
| Other streptococci | NF | NF | P | P | NF | NF, P | P |
| Enterococcus spp . | P | P | P | P | NF, P | NF, P | P |
| Escherichia coli | NF, P | NF, P | P | P | NF, P | NF, P | P |
| Klebsiella pneumoniae | NF, P | NF, P | P | P | NF, P | NF, P | P |
| Enterobacter cloacae | NF, P | NF, P | P | P | NF, P | NF, P | P |
| Enterobacter aerogenes | NF, P | NF, P | P | P | NF, P | NF, P | P |
| Proteus spp . | NF, P | P | P | P | NF, P | NF, P | P |
| Serratia marcescens | NF, P | − | P | P | P | P | P |
| Other enterics | NF, P | NF, P | P | P | NF, P | P | P |
| Pseudomonas aeruginosa | P | NF, P | P | P | NF, P | P | P |
| Acinetobacter spp . | NF | NF | P | – | NF | NF | P |
| Candida albicans | NF | NF | P | P | NF | P, NF | P |
The organisms that predominate as causative agents of burn wound infection in any burn treatment facility change over time. For example, at Shriners Hospital for Children–Galveston, from 1989 to 1999, only 42% of children died of sepsis due to multidrug-resistant (MDR) organisms; in 25% of these children, Pseudomonas was the responsible organism. From 1999 to 2009, 86% of patients died of sepsis due to MDR organisms, and, in 64% of these children, again the cause was Pseudomonas infection. In this latter period, Acinetobacter also emerged as a major pathogen of death due to sepsis while the role of Klebsiella declined. In more recent years, there has been a further shift in the pathogens, described in the following sections.
Gram-Positive Bacteria
The gram-positive predominance is consistent with the normal inhabitants of the skin before the thermal injury. Staphylococcus spp., Micrococcus spp., Streptococcus spp., Pediococcus spp., and Enterococcus spp. are gram-positive cocci commonly encountered in burn wounds. Erol and colleagues demonstrated that coagulase-negative Staphylococcus and S. aureus were the most prevalent isolates in admission cultures, followed by diphtheroids. These organisms can be life threatening as invasive infections or simply be locally colonized. The distribution of gram-positive bacteria at Shriners Hospital for Children–Galveston, which receives pediatric burn patients from all over the world, is shown in Table 76.2 . In 2011, the gram-positive cocci accounted for 55% of bacterial isolates; however, by 2015, this rate had dropped to 46%. In this latter year, staphylococci were more prevalent (61%) than enterococci (29%). Interestingly the rates of methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) isolates were equal in 2011, but, by 2015, the MRSA rates had dropped by two-thirds. This recent downward shift in MRSA rates is in keeping with the overall pattern observed in the United States.
| No. (%) of Isolates | |
|---|---|
| Gram-Positive Organisms | |
| Coagulase-negative Staphylococcus | 131 (37.9) |
| Enterococcus faecalis | 63 (18.2) |
| Methicillin-sensitive Staphylococcus aureus | 55 (15.9) |
| Enterococcus faecium | 36 (10.4) |
| Other gram-positive organisms a | 36 (10.4) |
| Methicillin-resistant Staphylococcus aureus | 25 (7.2) |
| Total gram-positive isolates | 346 |
| Gram-Negative Organisms | |
| Enterobacteriaceae (Enterics) | |
| Klebsiella pneumoniae | 45 (11.1) |
| Escherichia coli | 34 (8.4) |
| Enterobacter cloacae | 34 (8.4) |
| Proteus mirabilis | 25 (6.2) |
| Escherichia coli (ESBL) | 24 (5.9) |
| Other Enterobacteriaceae b | 19 (4.7) |
| Klebsiella pneumoniae (ESBL) | 19 (4.7) |
| Klebsiella spp. | 16 (4.0) |
| Serratia marcescens | 15 (3.7) |
| Enterobacter spp. | 11 (2.7) |
| Morganella morganii | 11 (2.7) |
| Non-Enterobacteriaceae | |
| Pseudomonas aeruginosa | 60 (14.7) |
| Acinetobacter species | 53 (13.1) |
| Stenotrophomonas maltophia | 23 (5.7) |
| Other non- Enterobacteriaceae c | 16 (4.0) |
| Total gram-negative isolates | 405 |
| Total bacterial isolates | 751 |
| Gram-positive organisms | 46.1% |
| Gram-negative organisms | 53.9% |
a Includes other Enterococcus spp. ( n = 28); Streptococcus spp. ( n = 7); Leuconostoc spp. ( n = 1).
b Includes Citrobacter spp. ( n = 9); other Proteus spp. ( n = 2); Providencia spp. ( n = 8).
c Includes Aeromonas hydrophila ( n = 6); Alcaligenes spp. ( n = 7); Burkholderia cepacia ( n = 3).
Because of such resistance patterns, Cook stresses the importance of microbial surveillance and epidemiologic studies. This approach is thought to reduce the prevalence of MRSA, yet it may be inadequate for eradicating or preventing outbreaks. Minimizing transmission and infection is emphasized. However, Reardon and associates suggest that this process is time-consuming and requires extensive resources for little gain. Colonization with MSSA and MRSA in 86 patients was studied and found to have no significant changes on length of stay, number of operations, or mortality between these two organisms. However, the presence of either type of S. aureus significantly increased the number of surgical procedures performed and the lengths of stay. Many burn units report frequent colonization of burn patients with toxic shock toxin (TSS-1)–producing strains of staphylococci; however, their presence does not correlate well with increased morbidity or mortality rates.
In the past, group A β-hemolytic streptococcus frequently was the cause of epidemics in burn units, but it seldom is encountered today because of the frequent empirical use of antibiotics for manipulations of burn wounds. Other β-hemolytic streptococci belonging to groups B, C, E, F, and G can be encountered as well. Significant infection-control vigilance still is necessary because occasional clusters of outbreaks of group A streptococcal infection continue to be reported. Fortunately group A streptococcus remains uniformly sensitive to penicillins, hence prophylaxis and treatment are easily accomplished.
Although enterococcal infections ( Enterococcus faecalis and E. faecium ) account for only 22% of burn wound infections caused by gram-positive bacteria (see Table 76.2 ), a significant cause for concern is the emergence of vancomycin-resistant Enterococcus (VRE) in burn units. Although additional morbidity associated with VRE itself is not clear, when it occurs as a polymicrobial bacteremia, a mortality rate as high as 20% has been noted.
Other gram-positive bacilli include the aerobic Corynebacterium spp. and Listeria spp., as well as the spore-forming Bacillus spp. (aerobe) and Clostridium spp. (anaerobe). Bacillus spp. and Clostridium spp. are associated with burn wounds that have come in contact with contaminated soil. In avascular muscle injuries (e.g., electrical injuries or crush injuries combined with burns), the risk for developing tetanus (from infection with Clostridium tetani ) is high and has led to the practice of using tetanus immunoprophylaxis and booster vaccines.
Gram-Negative Bacteria
The presence of the gram-negative bacteria in burn wounds is due in part to translocation of the bacteria from the gastrointestinal tract of the patients. In a study of children with burns at Shriners Hospital for Children–Galveston, patients with large wounds (>50% TBSA) were found to have significantly higher colonization with their fecal gram-negative bacteria than were those with smaller wounds. P. aeruginosa bacteremia is predicted by isolation of P. aeruginosa from another site (wound, urine, or sputum), and the prior nonblood isolates of P. aeruginosa can correctly predict the antimicrobial sensitivity pattern in 75% of patients. At Shriners Hospital for Children–Galveston, gram-negative bacteria accounted for 54% of the total bacterial isolates of wounds in 2015 (see Table 76.2 ). Indeed, the rates increased from 2011 when it accounted for 48% of total isolates. A significant proportion of these bacteria produce extended spectrum β-lactamase (ESBL) enzyme. Escherichia coli and Klebsiella pneumoniae are the predominant ESBL-producing bacteria. Bennett and coworkers have shown that infections caused by ESBL-producing K. pneumoniae are predictive of death when occurring in older persons.
Although the carbohydrate-fermenting Enterobacteriaceae account for 64% of the gram-negative isolates as a whole, P. aeruginosa and other nonfermenters are also important in burn patients. Other important gram-negative bacteria include the Enterobacteriaceae such as E. coli, Enterobacter cloacae, K. pneumoniae, and Serratia marcescens. Enterobacteriaceae also are encountered as a cause of nosocomial pneumonia in patients with inhalation injury who are on ventilators, and they are a cause of urinary tract infection in patients with indwelling urinary catheters . Acinetobacter , an increasingly more common cause of gram-negative infections, has been found more frequently in burn patients with glucose intolerance or preexisting diabetes mellitus and in patients with more severe burns and comorbidities.
Even without invasive infections, gram-negative bacteria have been implicated in systemic inflammatory diseases, including shock and disseminated intravascular coagulation, secondary to the circulation of bacterial endotoxin from the gut and the burn wound. Often gut decontamination is instituted to reduce the incidence of endotoxin-mediated disease.
Fungi
Until the advent of topical antimicrobial agents and systemic antibiotics, fungal infections were not common developments in patients with burns. The burn wound is the site most commonly infected, although fungemia and dissemination to the respiratory tract in patients on ventilators and to the urinary tract in patients with indwelling catheters are encountered frequently. Candida spp. are the most common fungal colonizers of the wound; however, fewer than 20% of patients develop widespread candidiasis. Overall the rate of candidemia in the burn patient population is 3% to 5%, and burn wound invasion has a comparable rate. A study of children with burn injury at Shriners Hospital for Children–Galveston showed that those developing candidemia did so during the first week after the burn and 7 days after excision of burn eschar. One hypothesis is that massive burns with immunosuppression are further suppressed by repeated surgical intervention, anesthesia, and perioperative use of broad-spectrum antibiotics, further predisposing these patients to early development of Candida septicemia. In one study, the attributable mortality rate with candidemia was 15%. With early recognition of invasion of burn wounds by routine biopsies, wound swabs, and early amphotericin therapy, the mortality rate has been reduced to less than 10% compared with 60% to 90% reported in earlier series.
Unlike Candida, true fungal infections caused by Aspergillus, Penicillium, Rhizopus, Mucor, Rhizomucor, Fusarium, and Curvularia occur early in the hospital course, specifically in those exposed to the spores on the ground or in water at the time the injury occurred. Once colonized, broad nonbranching hyphae extend into subcutaneous tissue and stimulate an inflammatory response. Vascular invasion occurs frequently and often is accompanied by thrombosis and avascular necrosis, which is clinically observed as rapidly advancing dark discolorations of the wound margin. Systemic dissemination occurs with invasion of the vasculature.
Viruses
Linnemann and MacMillan performed a retrospective survey of serum for viral antibodies in pediatric burn patients; 22% had fourfold increases in antibodies to cytomegalovirus (CMV), 8% had increases to herpes simplex virus (HSV) and to Epstein-Barr virus, and 5% had increases in antibodies to varicella zoster virus (VZV). None of the patients had evidence of adenovirus or hepatitis B virus infection. On the basis of these observations, a prospective study of viral infections using both serologic and viral culture techniques was performed. This study showed that CMV infection developed in 33% of the children, HSV infection occurred in 25%, and adenovirus infection was noted in 17%. CMV infections developed in all of the most severely burned children, and both primary and reactivation infections were observed. Most primary CMV infections that develop during treatment for burns are likely to occur from transfusion of blood products. CMV infection typically occurs approximately 1 month after the burn occurs and clinically presents as fever of unknown origin with lymphocytosis; however, it rarely alters the patient’s clinical course. Kealey and colleagues have shown that 56% of burn patients who initially were seropositive for CMV had a fourfold or greater rise in CMV antibodies as evidence of CMV reactivation. These patients tended to be younger, to have a larger burn area, and to have a longer hospital stay. No patient who experienced CMV infection, whether primary or reactivated, had serious complications attributable to CMV. On the basis of these observations, despite the availability of anti-CMV agents such as ganciclovir and valganciclovir, treatment of CMV infection remains controversial.
Since the screening of blood began, hepatitis C virus (HCV) has been an important risk factor. Coursaget and colleagues screened 45 burn patients for anti-HCV antibodies at the time of burn injury and at more than 6 months after the burn. HCV infection was detected in 18% of these patients as a consequence of the numerous transfusions of blood or blood derivatives used during the postburn treatment. Five patients displayed evidence of anti-C100, anti-C33c, and anticore antibodies together; two patients had only anti-C100 and anti-C33c antibodies, and the last patient showed only anticore antibodies. Chronic hepatitis was observed in 83% of HCV infections. Kinetics of appearance of anti-HCV antibodies varied among patients. Anticore antibodies generally are the first to be detected at high levels; however, in at least one case, they were detected only 2.5 months after C100 and C33c antibodies were detected. The incidence of HCV using polymerase chain reaction (PCR) assay to detect the viral genome has not been evaluated in burn patients. Nonetheless the current procedures used at blood banks have decreased the transmission of HCV by blood products.
Another transfusion-related agent is human immunodeficiency virus (HIV), which has become extremely rare as a result of the screening of donors that began in 1987 in the United States. However, significant risk existed prior to that period. A retrospective review of children with burn injury at Shriners Hospital for Children–Galveston who had received blood or blood products between 1978 and 1985 identified 52 patients at risk for developing HIV infection. More than 50% of the identified population had received three or more units of blood or blood products during their acute hospital stay. A total of 214 patients (36.8%) were tested for HIV seroconversions: five tested HIV positive by enzyme-linked immunosorbent assay (ELISA) and four were confirmed by Western blot, yielding a 1.9% incidence. The four confirmed patients received two to nine total-body blood volume turnovers during their postburn period in the hospital. HIV may affect the outcome of burn wound injury. A study of Malawian children showed that with burns affecting 11% to 30% of the body surface area, HIV-positive children had a mortality rate approximately twice that of HIV-negative children.
HSV is of significant concern in burn units because it is a dermatopathologic virus. A review of the literature suggests that patients younger than 10 years were at greater risk for acquiring an HSV infection when the size of the burn wound was greater than 15% TBSA. However, the role of HSV in the healing of wounds is unclear. Bourdarias and associates showed that, in 11 patients with burns, local areas of active epidermal regeneration were affected most often. Acyclovir therapy was not used, and the duration of hospitalization was normal when compared with that of other children. Nonetheless HSV in lungs may worsen morbidity. Byers and coworkers showed that the relative risk for developing HSV infection was higher for patients with acute respiratory distress syndrome but not for those with pneumonia. Disseminated HSV infection also can be fatal.
Another dermatopathologic virus is VZV. Mini-epidemics of VZV have occurred within pediatric burn units. With the routine VZV vaccination of young children (at 1 year of age) in the United States, outbreaks of varicella in burn units are now uncommon. The characteristic fluid-filled lesions appear in partial-thickness burns that are healed or healing, as well as in uninjured epithelium and mucous membranes. The vesicles are much more destructive in the injured than uninjured skin and may present as hemorrhagic, oozing pock marks that are prone to development of secondary infection and subsequent scarring. Neovascularized skin grafts may be lost; therefore further grafting procedures should be delayed until the lesions are quiescent.
The morbidity due to respiratory virus infections, particularly in those with inhalation injury, has not been studied well. We tested more than 100 pediatric burn patients for respiratory syncytial virus (RSV) during the winter seasons of 1995 and 1996. Only six patients were found to be positive for RSV, with one death (1% mortality rate).
Parasites
Parasitic infestation also is seen, especially in children from the developing world. Because we see many patients who originate from Mexico, where such infestation is endemic, parasitemia has been found to complicate burn injuries. Parasites that are asymptomatic in sites such as the intestinal tract and the respiratory tract can become symptomatic as a result of the stress of a burn injury. At the Shriners Hospital for Children–Galveston, we have described three cases of Ascaris pneumonitis that exacerbated smoke-induced lung injury. In 2006, the parasites isolated most frequently were Giardia lamblia and Blastocystis hominis.
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