Pediatric Burn Infection

The Inflammatory Response to Burn Injury Leading to Sepsis

Mild insults to the body cause low extents of inflammation or cytokine response that are localized or walled-off. However, with larger insults, as in severe burn injuries such as those encompassing at least 15% of the TBSA, inflammatory cells are deposited in the systemic circulation [2]. Inflammatory cells or cytokines are sensed by the hypothalamus, and there is a release of catecholamines and glucocorticoids, which fuel a systemic inflammatory response syndrome (SIRS) [2]. The physiologic responses to severe burn injury are more severe and more sustained than those of any other trauma [22]. The burn causes a 5- to 10-fold increase in circulating catecholamines and an 8- to 10-fold increase in cortisol that persist as long as three years after injury, long after closure of the wound [22]. Pro-inflammatory cytokines are increased as much as 2000-fold post-burn [22]. These cytokines are linked to cell proliferation, glucose metabolism, and insulin resistance. Dysregulated glucose metabolism is correlated with a higher risk of infection [22]. This persistent hyper-inflammatory state means that patients with large burns remain in a state of SIRS. The American Burn Association (ABA) held a Consensus Conference in 2007 to define sepsis in burn patients and published defining guidelines for the adult patient (Table 1) [23].

The ABA specified wound colonization using microbiologic criteria as bacteria present on the wound surface at concentrations <10⁵/g of tissue without signs of infection. It further defined wound infection as the presence of bacteria in the wound at a concentration >10⁵/g of tissue with signs of infection. Invasive infection was defined as the presence of pathogens in adjacent unburned tissue [23]. Further complicating the diagnosis of sepsis for the burn patient are the factors contributing to their critical care management. The larger the burn, the higher the likelihood that these patients will require urinary catheters, central venous lines, arterial lines, and ventilators, for the resuscitation, access, as well as multiple trips to the operating room. These tools along with the loss of skin barriers lead to higher risks for infection, immunosuppression, and septic episodes [23]. The key management principles in sepsis, regardless of whether the patient suffered a burn injury, is recognition of sepsis, resuscitation and stabilization of the patient, and sustained adherence to sepsis bundles [2].

Sepsis in Pediatric Burns

For pediatric burn patients, the ABA used the guidelines from the International Pediatric Consensus Conference. Because vital signs are age-dependent in the pediatric population, the ABA Consensus used diagnostic values suggested by the pediatric sepsis group: Heart rate and respiratory rate two standard deviations above age-specific norms. Thrombocytopenia also was adjusted to be less than two standard deviations below age-specific norms. For feeding intolerance, the accepted values were reset, and for diarrhea, the value was >400 mL/day. The values for septic shock were defined as greater than two standard deviations below normal for age to accommodate lower normal blood pressure along with higher heart and respiratory rates. In addition, the following signs were suggested: Tachycardia with signs of decreased perfusion, decreased peripheral pulses compared with central pulses, mental status changes, mottled extremities, and decreased urine output [2,24].

Once recognized, sepsis in the pediatric burn patient is managed with prompt goal-directed resuscitation, broad-spectrum antibiotics, and source control [2,5,6,24]. Surviving Sepsis Campaign Guidelines for children were published in 2020 [25]. Re-establishing or maintaining end-organ perfusion is paramount in the resuscitation. Age-appropriate vital sign goals and clearance of serum lactate represent adequate tissue perfusion [2,24].

Prompt initiation of antimicrobial agents is critical for surviving sepsis. Appropriate cultures should be obtained, ideally tissue culture, and intravenous antimicrobial drugs administered within an hour [2,5,12]. Most cases of sepsis in burn patients originate from infected burn wounds, with Pseudomonas aeruginosa and Staphylococcus aureus being the most common organisms [5,26]. However, multiple other organisms may be virulent in this patient population secondary to their loss of skin and presence of immunosuppression [5,26]. In general, the longer the patients have open wounds, the higher the risk is for infection. The causes of infections go from gram-positive to gram-negative organisms [27,28]. Pediatric burn patients also are at risk for fungal and viral infetions, as well as multi–drug-resistant organisms [5,26]. Once a source has been identified, de-escalating the antibiotics is recommended to decrease the risk of drug resistance [5,28].

For patients who fail to be resuscitated with fluids alone, vasoactive medications may be needed. The first line drug recommended by Surviving Sepsis Campaign for septic shock in adults is norepinephrine [5,12]. For pediatric patients, however, epinephrine often is preferred [2]. These drugs are followed by vasopressin or dobutamine depending on the need for inotropic support and the systemic vascular resistance of the patient [2,12].

After identifying the signs and symptoms of sepsis, resuscitation, and stabilization of the patient, timely source control improves outcomes and decreases the mortality rate. Debriding or excising the infected burn wound usually is the best source control for the burn patient where fascial excision may be needed [5,28]. With large burns, however, this may not be the only source. Wound infection is most common, but other sources of infection should be considered, as central venous lines, arterial lines, or urinary catheters may be the source of sepsis. Removing or changing these lines or catheters may provide effective source control [2,5,28].

Treatment

Although there are guidelines and common signs and symptoms [23], diagnosis is made on the basis of clinical findings, and treatment is guided by the microbiology results from a wound biopsy. Treatment options for burn infection include topical and systemic antimicrobial drugs, but surgical intervention often is definitive.

Investigators have reported differences in the distribution of organisms in burn wounds. The predominant colonization of the wound starts with gram-positive organisms, which are replaced by gram-negative organisms later in the course [27,28]. In fact, bacterial colonization, primarily with gram-positive organisms (Staphylococcus aureus) can reach more than 80% within the first week [27]. By the third week, gram-negative organisms such as P. aeruginosa are more prevalent [27]. Regardless of temporal relations, gram-positive organisms are responsible for more than half of infections [15,18,29]. Of note, evidence of the emergence of gram-negative organisms over gram-positive organisms has been published [30].

Globally, the incidence of multi–drug-resistant bacterial infection is on the rise [31]. Pediatric burn patients are no exception. This makes optimal antimicrobial therapy challenging [32]. Multi–drug-resistant P. aeruginosa and Acinetobacter baumannii were the most common [33]. Pan-resistant P. aeruginosa and A. baumannii have been seen more frequently in burn patients, including pediatric burn patients [23].

Because of the emergence of pan-resistant gram-negative organisms and the paucity of newly developed effective antibiotics, other antimicrobial drugs, such as colistin, have been employed [31,34]. Colistin is of the polymyxin family (polymyxin E), with bactericidal activity against gram-negative organisms [34]. Infections with pan-resistant P. aeruginosa and A. baumannii were treated with colistin in burned children with some success [34]. However, emergence of colistin resistance is now being seen in relation to increased usage [31]. Specifically, A. baumannii and P. aeruginosa resistant to all tested antibiotics including colistin have been documented in burn patients [35].

Topical antimicrobial drugs are indicated for all burn wounds. They consist of creams, ointments, or solutions that often address both gram-positive and gram-negative organisms and work to prevent burn wound infection, graft failure, invasive infection, and burn sepsis [36]. Prophylactic, systemic antimicrobial drugs are not indicated in burns. Systemic antimicrobial drugs are not effective against wound colonization, and the avascular burn eschar and biofilms prevent adequate delivery of the systemic drugs to the wound [36]. Routine use, without appropriate microbiology culture data, may lead to multi-drug resistance [28,36]. The emergence of multi–drug-resistant organisms increases morbidity and deaths [6,28,32].

Excision of burn eschar, removing the source of potential infection, is a key component of treatment as well as prevention of infection. One of the ways to decrease bacterial colonization of burn wounds is removal of eschar as soon as possible before infection occurs. Early excision of eschar also decreases the incidence of invasive burn wound infection [37].

As long as burn wound is present, the risk of infection persists. Therefore, most authorities advocate early excision and grafting [1,38]. Barret et al. showed that wound excision within the first 24 hours after injury significantly decreases bacterial colonization and subsequent infection in pediatric burn patients compared with topical antimicrobial drugs and delayed burn excision [38]. Despite early excision of eschars, patients still are at risk for infection, and this correlates with burn size because of the significant loss of the protective barrier from the environment and immunosuppression associated with large burns [2]. Thus, expeditiously restoring the protective barrier by excising the burn wound and grafting to achieve healing is the hallmark of effective burn management.

Conclusion

Severe burns lead to a profound hypermetabolic, hyper-inflammatory state. Pediatric burn patients are at greater risk for infection and sepsis secondary to the injury and resultant immunosuppression. Key principles in improving outcomes for septic pediatric burn patients is early recognition, resuscitation, and adherence to management strategies such as prompt antimicrobial drug administration and source control.