Burn wound infection and sepsis

INTRODUCTION — Infection remains the most common cause of morbidity and mortality in burn patients. The diagnosis and management of burn wound infection remains challenging due to the many physiologic features unique to burn injury. A variety of factors increase the risk of developing burn wound infection, and individuals who sustain a severe burn have a particularly high risk for burn wound sepsis.

Any rapid change in the burn wound appearance or the clinical condition of the burn patient may herald burn wound infection or sepsis. The different categories of burn wound infection are characterized based on clinical features and depth of invasion, which is determined through cultures and histopathology of tissue obtained by burn wound biopsy. A diagnosis of burn wound infection relies on the demonstration of >10⁵ bacteria per gram tissue (or recovery of mold or yeast by culture). Specific criteria that include the presence of microbial invasion into adjacent normal tissue, among other criteria, have been suggested by the American Burn Association (ABA) to define burn wound sepsis.

The most common organisms remain Staphylococcus and Pseudomonas; however, the epidemiology of burn wound infections has changed with time and also depends on geography. It is imperative to be aware of the flora and susceptibility of organisms in each burn unit to be able to treat burn wound infections effectively.

Depending upon the burn wound category, treatment of burn wound infection/sepsis consists of a combination of wound cleansing, debridement, topical or systemic antimicrobial therapy, and burn wound debridement or excision.

The clinical manifestations, diagnosis, and treatment of burn wound infection and sepsis are reviewed here. Sepsis related to other conditions is reviewed elsewhere. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis".)

EPIDEMIOLOGY AND RISK FACTORS — The incidence of burn wound sepsis has declined from 6 to 1 percent since the practice of early burn wound excision; however, for patients with total body surface area (TBSA) burns >15 percent, the rate has remained the same [1,2]. The highest rates of surgical burn wound infections occur in the lower extremities, but specific organisms or classes of organisms are not confined to one particular anatomic location [3].

Patients with burn wounds also have high rates of other types of infection, such as catheter-related infection [4,5]. In a series of 175 patients with severe burns, infections preceded multiorgan dysfunction in 83 percent of patients and were considered the direct cause of death in 36 percent of those who died [6].

Risk factors — A variety of factors increase the risk of developing invasive burn wound infection (burn wound sepsis). Individuals who sustain a TBSA burn >20 percent are at particularly high risk; however, burn wound infection and sepsis can occur in smaller burns [4,6-8]. Other risk factors include delays in burn wound excision, extremes in age (very old, very young), and impaired immunity. Microbial factors, such as type and number of organisms, enzyme and toxin production, and motility, also contribute [4,9-13].

In the management of burn wounds, topical therapy is associated with a higher incidence of burn wound infection and graft loss compared with early excision and grafting. Delaying burn wound excision increases bacterial loads and gram-negative colonization. When bacterial counts exceed 10⁵ organisms per gram of tissue in the burn eschar, wounds should be considered at risk for developing invasive burn wound infections, even when the wounds are excised. Despite the ability of burn wound excision to decrease bacterial counts, burn wounds with high counts are at risk of developing burn wound sepsis both before and after surgery [14]. (See 'Wound colonization' below and "Overview of surgical procedures used in the management of burn injuries".)

PATHOGENESIS — Burn injury is associated with profound alterations in metabolic and host defense mechanisms and immune function, which predisposes burn patients to local and systemic invasion by microbial pathogens [15-18]. The burn wound is also susceptible to opportunistic colonization by endogenous and exogenous organisms. Colonization of burn wounds by endogenous and/or exogenous organisms often occurs as biofilms [19-21]. The spectrum of microorganisms causing infection in burn patients varies not only with geographical location but also has changed with time, and, thus, it is necessary to review the bacterial flora colonizing burn patients on a regular basis [22,23]. (See 'Wound colonization' below.)

An intact, healthy skin surface has bacteriostatic properties that normally limit the degree of skin colonization by pathogens and noninvasive resident microbes. Low levels of bacteria that colonize the burn wound stimulate the inflammatory response, activate macrophages, and produce growth factors and cytokines that aid in wound healing. They also prevent overgrowth of nonresident bacteria. (See 'Microbiology' below.)

Burned patients lose their protective primary barrier (skin) to environmental microorganisms. The burn also consists of avascular necrotic tissue (eschar) that provides a protein-rich environment favorable to microbial colonization and proliferation [9,10,14]. The avascularity of the eschar impairs migration of host immune cells and restricts delivery of systemically administered antimicrobial agents, while toxic substances released by eschar tissue impair local host immune responses [10].

MICROBIOLOGY — The spectrum of microorganisms causing infections in burn patients varies with time and location (table 1). The organisms causing burn wound infection typically appear at varying stages post-burn-injury (table 1) [4]. Immediately after burning, the microbial population of the burn wound is sparse and includes predominantly gram-positive bacteria that survived the thermal insult, such as staphylococci located deep within sweat glands and hair follicles [4,11]. Within the first week post-burn, burn wounds are colonized with other microbes, such as gram-positive bacteria, gram-negative bacteria, and yeasts derived from the patient's normal gastrointestinal or upper respiratory tract flora, and from the hospital environment [4,9-11]. The predominant gram-positive organisms found in burn wound infections remain Staphylococcus aureus, followed by Enterococcus species, which are found in decreasing numbers (table 1). Gram-negative pathogens dominate after the fifth day of a typically protracted in-hospital stay and have emerged as the most common etiologic agents of invasive infection by virtue of their large repertoire of virulence factors and antimicrobial resistance traits [10,24]. Pseudomonas aeruginosa remains the most frequent gram-negative microorganism isolated from burn wounds, followed by Escherichia coli.

With severe burn-associated immune deficiency and/or delayed or inadequate treatment, microbial invasion of viable tissue occurs, which represents the hallmark of an invasive burn wound infection [10]. Fungi (eg, Candida, Aspergillus, Fusarium, Mucor species) and multiresistant organisms (eg, methicillin-resistant Staphylococcus aureus [MRSA], vancomycin-resistant Enterococcus [VRE], Acinetobacter) appear late in chronological appearance and typically occur after use of broad-spectrum antibiotics and/or a prolonged hospital stay [10]. Candida spp is the most common fungus isolated from burn wounds and the fourth most common cause of burn wound infections overall [7], and herpes simplex virus type 1 (HSV-1) remains the most common viral organism in burn wounds [10]. The characteristic physical findings of these common organisms are described in the table (table 2). Emerging multidrug-resistant strains of bacteria and fungi have caused an unanticipated rise in burn wound infections, sepsis, and associated death worldwide [7,25-28]. Infections with MRSA, Stenotrophomonas maltophilia, and Acinetobacter spp have become more frequent and increasingly more difficult to treat as these species are becoming more often resistant to the antibiotics traditionally used to treat them [22,23]. (See 'Burn wound appearance' below.)

CLINICAL FEATURES — A rapid change in the clinical condition of the burn patient may indicate that burn wound infection, and potentially burn wound sepsis, is present.

Patients with invasive burn wound infections (burn wound sepsis) may have fever, other signs of sepsis, changes in wound appearance (eg, purulent drainage, erythema, tenderness), or increased pain. (See 'American Burn Association criteria for burn wound sepsis' below.)

Patients who had previously tolerated enteral feedings may show signs of intolerance (eg, abdominal distention, increase in residual volume, uncontrollable diarrhea). (See "Nutrition support in intubated critically ill adult patients: Enteral nutrition", section on 'Monitoring and management of complications' and "Overview of enteral nutrition in infants and children", section on 'Monitoring'.)

Physical examination — Burn wound infections are most often recognized based upon the gross appearance of the burn and/or skin graft donor site, and alterations in clinical measurements (eg, vital signs, abdominal distention). The burn wounds should be carefully examined with each dressing change, particularly in those that will not be changed on a daily basis.

Burn wound appearance — Early diagnosis and treatment of burn wound infection relies on recognition of an infected burn wound site. The most common clinical feature is a rapid change in the appearance of the wound, which may include conversion of a partial-thickness injury to full-thickness injury, or loss of previously viable tissue or skin graft.

Acute bacterial infection manifests with the development of discoloration, pain, purulent exudate, edema, tenderness, swelling, drainage, or malodor from a burn or burn-related wound (previously reepithelialized grafted burn site, skin donor site). The appearance of infection may involve only a portion of the burn wound. A surrounding cellulitis can occur and is characterized by erythema involving uninjured skin and may also exhibit localized pain and tenderness, swelling, and warmth. Peri-burn cellulitis may be indicative of infection beyond the borders of the burn wound and into normal tissue and signals the possibility of invasive infection. Infection may also lead to ischemia, necrosis, or loss of synthetic or biologic covering.

Local signs and characteristics of burn wound infections caused by fungi include unexpectedly rapid separation of the eschar, presumably due to fat liquefaction, and rapid spread of subcutaneous edema with central ischemic necrosis (table 2) [29]. Vesicular lesions that appear 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 nasolabial area, are characteristic of burn wound infections caused by herpes simplex virus type 1 (HSV-1) [30].

The most reliable local sign of invasive burn wound infection (burn wound sepsis) 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 or skin graft. Such necrosis appears as focal, multifocal, or generalized dark brown, black, or violaceous discoloration of the wound or graft, or as overt sloughing of a previously adherent graft [31].

Other characteristics of invasive burn wound infection include [4,9-11,29,31]:

●Edema and/or violaceous discoloration at the margin of the burn and/or unburned skin

●Hemorrhagic discoloration of subeschar tissue

●Separation or discoloration of the burn eschar

●Presence of green pigment (pyocyanin) in subcutaneous fat (indicative of Pseudomonas infection)

●Presence of initially erythematous and later black necrotic nodular lesions (ecthyma gangrenosa) in adjacent unburned skin

●Exophthalmos may be the first sign of mucormycosis in midface burns (retrobulbar space involvement)

Systemic signs — Severely burned patients lose their primary barrier to invasion by microorganisms, and, as such, they are constantly exposed to the external environment. Such exposure leads to substantial elevations in the white blood cell (WBC) count, making leukocytosis a poor indicator of sepsis [25].

Systemic signs of sepsis include tachycardia, tachypnea, hypotension, oliguria, unexplained hyperglycemia, thrombocytopenia, and mental status change (eg, confusion). The following systemic findings are associated with invasive burn wound infection (burn wound sepsis) (see 'American Burn Association criteria for burn wound sepsis' below):

●Temperature >39°C or <36.5°C

●Progressive tachycardia (eg, adults >90 beats per minute; children >2 standard deviations [SD] above age-specific normal values) (table 3 and table 4) [32]

●Progressive tachypnea (eg, adults >30 breaths per minute; children >2 SD above age-specific normal values) (table 3 and table 4) [32]

●Refractory hypotension (eg, adults: systolic blood pressure <90 mmHg or a decrease >40 mmHg, or mean arterial pressure <70 mmHg; children <2 SD below normal)

The continuous release of inflammatory mediators alters the baseline metabolic profile of the burn patient [33]. Baseline temperature is reset to approximately 38.5°C, and tachycardia and tachypnea persist for months in patients with extensive burns [34,35]. Patients who have only signs of hypermetabolism without other signs of sepsis must be distinguished from typical changes associated with the hypermetabolic response to thermal injury. (See 'Hypermetabolic response to thermal burn' below.)

In one retrospective review of 110 patients admitted to a burn unit with a wide range of burn wounds, 56 patients (50 percent) developed early infection and 18 developed early sepsis [12]. Logistic regression identified maximum temperature ≥39°C and FiO₂ >25 percent (surrogate marker for respiratory problems) as significant predictors of burn wound sepsis within the first 10 days of injury. In addition, predictors of early sepsis (within 10 days of burn) included heart rate ≥110 beats per minute, systolic blood pressure ≤100 mmHg, and intubation.

Laboratory findings — For patients in the intensive care unit, routine laboratory studies are typically obtained at least daily, but for those being cared for in a less intense setting, often they are obtained only as needed.

The following laboratory alterations in blood tests can be found in patients with burn wound sepsis:

●Glucose – Fasting serum blood glucose levels >110 mg/dL (6.1 mmol/L) in the absence of preexisting diabetes mellitus. (See "Hypermetabolic response to moderate-to-severe burn injury and management", section on 'Altered glucose metabolism'.)

●White blood count – Leukocytosis (>12,000 cells/microL, adults; >2 SD above the normal level for children (table 3); or leukocytopenia <4000 cells/microL).

●Platelet count – Platelet count <100,000/microL (adults), <2 SD below the normal level for children.

●Procalcitonin – For patients with severe burns, daily measurements of serum procalcitonin (PCT) may be useful for monitoring the effectiveness of antibiotic therapy. The value of serum PCT concentration for differentiating bacterial infection from other causes of postoperative fever has been explored in patients with burn wound sepsis [36,37]. However, postoperative PCT concentrations are quite variable, particularly in postoperative patients, and as a result, a specific threshold value is difficult to determine [38]. In a systematic review that identified 566 PCT samples among burn patients in nine trials, cutoff values above which a positive result was defined ranged from 0.53 to 3 ng/mL. For similar cutoff values, the sensitivity and specificity of PCT also varied widely [36].

DIAGNOSIS — When burn wound infection is suspected clinically based upon the clinical features discussed above, qualitative wound cultures can identify the presence of flora, but quantitative wound cultures (number of bacteria per gram of tissue) and histopathology obtained by biopsy of the wound are required to confirm the diagnosis of burn wound infection (algorithm 1). In an infected burn wound, bacteria are present at concentrations >10⁵ bacteria per gram of tissue [39,40]. The presence of bacteria at concentrations >10⁵ bacteria per gram of tissue in adjacent unburned tissue defines invasive burn wound infection. Systemic symptoms are usually present in patients with burn wound sepsis related to invasive burn wound infection.

Wound culture, tissue biopsy, and histopathology — Surface wound cultures are useful for identifying predominant organisms of the burn wound flora. Swab cultures assist in the surveillance of the bacterial flora colonizing burn patients [22,23,39,40]. Burn wounds are swabbed on admission and again if there are any concerning changes in appearance. In the absence of changes, weekly surveillance swabs are suggested. However, the only reliable way to differentiate noninvasive from invasive burn wound infection is by histopathology from a burn wound biopsy [4,14,40,41]. Tissue histopathology allows for quantification and evaluation of infection depth and extent of involvement [10]. The tissue biopsy samples should be obtained from several of the affected areas of the burn wound and should be approximately 1 to 2 cm in length and 1.5 cm deep and extend into the subcutaneous tissue, or weigh approximately 0.5 grams. Although a presumptive diagnosis of infection can be made when bacterial count is >10⁵ organisms per gram of tissue, quantitative cultures are more helpful for confirming the absence of wound infection (<10⁵ organisms per gram of tissue). The correlations between negative culture results (<10⁵ bacteria per gram of tissue) and negative histopathology is 96 percent; however, positive quantitative cultures (>10⁵ bacteria per gram of tissue) correlate with tissue invasion in only 36 percent of cases [40]. The specific histologic sign of invasive burn wound infection is the presence of microorganisms in adjacent normal, unburned tissue [4,10,14,40,41].

Other histologic findings indicative of invasive 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 subeschar space (a site of microbial proliferation prior to invasion), and intracellular viral inclusions typical for HSV-1 infections (table 2). An invasive fungal disease is diagnosed by identifying hyphae or melanized yeast-like forms using histopathologic, cytopathologic, or direct microscopic examination of a biopsy or needle aspiration specimen [42]. These findings are accompanied by histopathologic evidence of associated tissue damage or recovery of a mold or yeast by culture of a specimen obtained from a normally sterile site, or by a radiological abnormality consistent with an infectious disease process.

Burn wound categories — The categories of burn wound infection are characterized based upon clinical features and extent and depth of microbial invasion, which can only be determined via histopathology [25]. (See 'Wound culture, tissue biopsy, and histopathology' above.)

Wound colonization — Colonization is present when bacteria are cultured from the burn wound surface at concentrations <10⁵ bacteria per gram tissue, in the absence of clinical or histopathologic evidence of infection or invasion of unburned tissue [10]. Semiquantitative culture of wound exudate or tissue will determine if there is growth within less than 24 hours for most microorganisms [43]. Colonization does not generally impair wound healing. For patients with concerning changes and systemic signs, a wound biopsy would be beneficial, which is typically performed during the operative excision of any necrotic or infected tissue. (See 'Wound culture, tissue biopsy, and histopathology' above.)

While colonization of a wound is not indicative of invasive infection, the presence of endogenous and or exogenous organisms in biofilms increases the risk. The organisms on burn wounds form complex polysaccharide matrices excreted by the organisms that make treatment challenging. In fact, the bacteria in biofilms are protected from the actions of antimicrobials by slowing the metabolic rate and growth pattern of the bacteria. This subsequently leads to persistent colonization, impaired epithelialization, and increased risk for systemic infection [19-21]. (See "Basic principles of wound healing", section on 'Epithelialization'.)

Noninvasive infection — Noninvasive burn wound infection is present when there are typical clinical features of infection without systemic signs, and the bacterial count is >10⁵ bacteria per gram of tissue (or recovery of mold or yeast by culture) obtained from a burn wound or eschar with no invasive component (ie, no microbial invasion into unburned tissue) as identified by tissue histopathology. This bacterial burden results in impaired skin and tissue graft take and promotes systemic infection.

Subcategories of noninvasive infections include the following:

●Noninvasive burn wound cellulitis – Noninvasive burn wound cellulitis is present when clinical features of infection extend into healthy, uninjured skin and soft tissue, and the bacterial count is >10⁵ bacteria per gram of tissue (or recovery of mold or yeast by culture) with no invasive component (ie, no microbial invasion into unburned tissue) identified by tissue histopathology.

●Burn-related surgical site infection – Burn-related surgical site infection is present when there are typical clinical features of infection without systemic signs, and the bacterial count is >10⁵ bacteria per gram of tissue (or recovery of mold or yeast by culture) obtained from an excised burn wound, or skin donor sites that have not yet reepithelialized with no invasive component (ie, no microbial invasion into unburned tissue) identified by tissue histopathology.

●Burn wound impetigo – Burn wound impetigo is the loss of epithelium due to an infection at a previously reepithelialized surface, such as a grafted burn, a partial-thickness burn allowed to heal by secondary intention, or a healed skin donor site. It is not related to inadequate excision of the burn, mechanical disruption of the graft, or hematoma formation.

Invasive infection — Invasive burn wound infection is present when there are typical clinical features consistent with burn wound infection (eg, erythema, wound drainage), associated with systemic signs, and bacterial count is >10⁵ bacteria per gram of tissue obtained from a burn wound or eschar with an invasive component (ie, microbial or fungal invasion into unburned tissue) identified by tissue histopathology. Necrotizing infections, which are aggressive infections involving the deeper tissues with the potential to cause extensive tissue necrosis, can occur.

A diagnosis of an invasive burn wound infection and sepsis should be made based upon the American Burn Association (ABA) consensus criteria given below. Although there are other excellent criteria for the diagnosis of infection and sepsis in most patients, the standard diagnosis is not optimal for burn patients [25]. Standardized definitions for sepsis and infection that are specifically applicable to the burn patient were developed in 2007 [25]. The burn sepsis definition distinguishes the change in patient status as a result of a microbial infection from changes that occur secondary to the hypermetabolic response of the burn itself. (See 'Differential diagnosis' below.)

The diagnosis of burn sepsis based upon the ABA definition has been challenged by Mann-Salinas [44]. Two later publications determined that Sepsis-3 definitions [45] outperformed both the Mann-Salinas and ABA criteria in predicting sepsis in burn patients [46,47]. However, neither has displaced the use of ABA definition as the standard.

American Burn Association criteria for burn wound sepsis — The ABA criteria are as follows [25,34,35]:

●Fulfillment of one of the following three criteria:

•Pathologic infection is confirmed on a culture (eg, wound, blood, urine), or

•Pathologic tissue source is identified (ie, >10⁵ bacteria on quantitative wound tissue biopsy or microbial invasion on biopsy), or

•Improvement in the clinical setting is attributed to antimicrobial administration

●And at least three of the following parameters:

•Temperature >102.2°F (39°C) or <97.7°F (36.5°C)

•Progressive tachycardia (eg, adults >90 beats per minute; children >2 standard deviations [SD] above age-specific normal values [32]) (table 3 and table 4)

•Progressive tachypnea (eg, adults >30 breaths per minute; children >2 SD above age-specific normal values [32]) (table 3 and table 4)

•Refractory hypotension (eg, adults: systolic blood pressure <90 mmHg or a decrease >40 mmHg, or mean arterial pressure <70 mmHg; children <2 SD below normal) (table 3)

•Leukocytosis (eg, adult >12,000 white cells/microL, children >2 SD above normal) or leukocytopenia (eg, <4000 white blood cells/microL) (table 3)

•Thrombocytopenia that occurs three days after resuscitation (eg, adults <100,000 platelets per microliter; children <2 SD below age-specific normal values)

•Hyperglycemia >110 mg/dL (6.1 mmol/L) in the absence of preexisting diabetes mellitus

•Inability to tolerate enteral feedings for more than 24 hours based upon:

-Abdominal distention

-Residual volumes (two times the feeding rate in adults and >150 mL/hr in children)

-Uncontrollable diarrhea (>2500 mL/day for adults and >400 mL/day for children)

Improving the ability to rapidly identify burn sepsis (or those at risk) is the subject of ongoing study. One group identified six variables (heart rate >130 beats per minute, mean arterial pressure <60 mmHg, base deficit <-6 mEq/L, temperature <36°C, use of vasoactive medications, and glucose >150 mg/dL) that may help with early prediction of burn wound sepsis [44].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of burn wound infection includes mainly burn wound colonization but may also include other conditions that can affect the skin in critically ill patients. Colonization of the burn wounds is distinguished from burn wound infection and infection-related problems by the absence of the accompanying clinical features discussed above, in spite of the presence of bacteria, which will have low counts. (See 'Wound colonization' above.)

Medication-related mucocutaneous reactions — Reactions to medications superimposed on burn wounds might be confused as burn wound infection or sepsis; however, in most cases dermatologic reactions are widespread (ie, would also involve unburned skin) and generally involve the mucous membranes. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are examples of such mucocutaneous reactions (table 5). The skin changes are characterized by widely distributed cutaneous erythematous macules or patches, and/or diffuse cutaneous erythema (picture 1A-D). TEN begins with a prodrome of fever and malaise, high fever (102.2°F [39°C]). In the early stages, skin pain may be prominent and out of proportion to clinical findings. The skin lesions can progress to full-thickness epidermal necrosis. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)

Hypermetabolic response to thermal burn — Burn wound sepsis should not be confused with the normal hypermetabolic response to thermal injury. Following burn injury, the continuous release of inflammatory mediators alters the baseline metabolic profile of the burn patient; baseline temperature is reset to approximately 101.3°F (38.5°C), and tachycardia and tachypnea persist for months [25,34,35]. The metabolic rate increases in proportion to the size of the burn, with increasing energy expenditure. As an example, adults with a 25 percent total body surface area (TBSA) burn injury develop a metabolic rate between 118 to 210 percent of the predicted basal metabolic rate; children with burn injuries greater than 40 percent TBSA develop a metabolic rate of 180 percent of the predicted basal metabolic rate. (See "Hypermetabolic response to moderate-to-severe burn injury and management".)

Other cause of sepsis — Burn wound sepsis needs to be distinguished from other causes of sepsis that commonly affect critically ill patients (eg, catheter-related infection, urinary infection, pneumonia, others in those with combined burn trauma injury), and from noninfectious entities that can mimic many of the systemic features of sepsis (table 6).

Physical examination or isolation of a pathogen in blood, urine, or sputum cultures may suggest an alternative source for sepsis (table 7). In a review of 5524 burn patients, the most common health-care-associated infections were bloodstream infections, followed by skin and soft tissue infections, urinary tract infections, and ventilator-associated pneumonia. While skin and soft tissue infections presented first, the fact that bloodstream infections were the most common underscores the importance of ruling out other sources [48]. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Septic focus identification and source control'.)

TREATMENT — Treatment depends upon the burn wound category and consists of a combination of burn wound care (ie, cleansing, dressings), antimicrobial therapy (topical with or without systemic agents), and burn wound excision or debridement. For patients found to have only wound colonization (no burn wound infection), treatment is conservative and aimed at preventing infection. (See "Overview of the management of the severely burned patient", section on 'Burn wound management'.)

Systemic antimicrobial therapy to treat fever in the absence of clinical symptoms and signs of burn wound infection is discouraged, particularly since burn patients typically have increased body temperature secondary to the systemic inflammatory response to burn injury. Although perioperative administration of systemic antibiotics in large percentage total body surface area burns has been associated with a reduced rate of surgical burn wound infection, there has been no correlation with improved mortality, and such antibiotic use has increased the prevalence of resistance of bacteria [49]. (See 'Hypermetabolic response to thermal burn' above.)

Noninvasive burn wound infection — For noninvasive burn wound infection, treatment consists primarily of topical antimicrobial therapy and burn wound excision for unexcised wounds, and possibly reexcision for excised wounds. (See 'Noninvasive infection' above.)

If there is significant peri-burn wound erythema (even in the absence of invasive infection and/or empirically while awaiting burn wound cultures and histopathology), we initiate treatment with intravenous cefazolin or clindamycin, or vancomycin if there is suspicion for MRSA, with or without an oral fluoroquinolone for burns involving the lower extremity or feet or burns in patients with diabetes. Burn wound impetigo is also treated using systemic antimicrobial therapy and possibly topical glucocorticoids [50]. Contact precautions should be used until 24 hours after the start of antibiotic therapy to avoid spread of impetigo [51]. (See "Impetigo", section on 'Treatment'.)

Local management of infected burn wounds includes cleansing, debridement, topical antimicrobial agents (eg, silver sulfadiazine, combination antibiotics, chlorhexidine), and dressings (eg, compresses, biosynthetics, biologics). The treatment for unexcised deep burn wounds is always excision; the required depth of excision depends on the depth of microbial invasion. Topical agents can be used initially for unexcised burn wounds to minimize bacterial burden until the excision can be performed [52]. (See "Overview of the management of the severely burned patient", section on 'Burn wound management' and "Treatment of superficial burns requiring hospital admission" and "Treatment of deep burns".)

Burn wounds that are already excised that become infected (ie, burn-wound-related surgical site infection) are also treated with topical therapy, and possibly reexcision depending upon the extent of involvement. The choice of topical agents depends upon the suspected or diagnosed microorganism as well as the availability of the agent on formulary [49,53-56]. (See "Topical agents and dressings for local burn wound care".)

Invasive burn wound infection — For patients with burn wound sepsis, initial management is aimed at stabilizing the patient and restoring perfusion.

●(See "Septic shock in children in resource-abundant settings: Rapid recognition and initial resuscitation (first hour)".)

●(See "Evaluation and management of suspected sepsis and septic shock in adults".)

Concurrently, we initiate empiric systemic broad-spectrum antimicrobial therapy, and once the patient is stabilized, we take the patient to the operating room to widely excise all infected tissue to a healthy tissue bed as determined by intraoperative biopsy. Invasive fungal infections need to be treated aggressively. Phycomycotic infections may be surrounded by a rim of edematous tissue, which must also must be excised.

The excised wounds need to be inspected again within 24 to 48 hours and debrided again if necrotic tissue is present, or if the wound is clean and no infected tissue remains and the wound appears viable, the burn wound can be covered with allograft [29,57-59].

Antibiotic choices depend upon the antibiogram of the individual institution. At the authors' institution, for burn wound sepsis we initiate empiric antimicrobial therapy with piperacillin/tazobactam or carbapenem or fourth generation cephalosporin, +/- vancomycin if there is suspicion for methicillin-resistant S. aureus (MRSA), +/- an aminoglycoside if there is suspicion for multidrug-resistant (MDR) P. aeruginosa. A suspicion for MRSA or MDR organisms is based on the typical flora found in each particular burn center. In addition, other patient factors such as the length of hospitalization, recent prior hospitalization, institutional status, immunocompromise, and use of empiric broad-spectrum antibiotics increase suspicion. The duration of therapy is based upon clinical response.

Specific antimicrobial therapy is guided by the results of burn wound culture and histopathology. Whenever possible, antimicrobial therapy should be directed toward the specific organisms isolated from the wound, blood, respiratory, and/or urine cultures [4]. When systemic antimicrobial therapy is needed, awareness should be heightened for the possibility of super-infection with resistant organisms, yeasts, or fungi. Phycomycotic infections benefit from both topical and systemic therapy [29,57-59]. However, systemic antifungal or antiviral agents should only be administered based on a proven diagnosis. (See 'Invasive infection' above and 'Microbiology' above and 'Wound culture, tissue biopsy, and histopathology' above.)

Specific antimicrobial therapies are reviewed elsewhere and include:

●(See "Clinical approach to Staphylococcus aureus bacteremia in adults".)

●(See "Staphylococcus aureus bacteremia in children: Management and outcome".)

●(See "Pseudomonas aeruginosa skin and soft tissue infections".)

●(See "Management of candidemia and invasive candidiasis in adults".)

●(See "Candidemia and invasive candidiasis in children: Management", section on 'Antifungal agents'.)

MORBIDITY AND MORTALITY — It is estimated that 75 percent of the mortality following thermal injuries is related directly to infections. Nosocomial infections (eg, central venous catheter source) and emerging multidrug-resistant strains of bacteria and fungi contribute to burn wound infections, sepsis, and associated death. The Nosocomial Infection Surveillance System from the US Centers for Disease Control and Prevention (CDC) reported that burn intensive care units (ICUs) have the highest rates of primary bloodstream infection in patients with central venous catheters among all ICUs [4,5]. In a series of 175 patients with severe burns, infection preceded multiorgan dysfunction in 83 percent of patients and was considered the direct cause of death in 36 percent of those who died [6].

Emerging multidrug-resistant strains of bacteria and fungi have caused an unanticipated rise in burn wound infections, sepsis, and associated deaths worldwide [7,25-28]. Studies have shown an increase in fungal/Candida rates in burn units [60,61]. However, these are not benign infections, as approximately 60 percent of all wound infections due to fungi/yeast require regrafting, and other studies have shown that Candida colonization and candidemia are associated with high mortality rates in burn patients [61-63].

Infection of burn wounds is not without consequence. The most common outcomes of burn wound infections include:

●Graft loss for excised and grafted burn wounds

●Increased number of surgical interventions

●Increased nosocomial infections

●Increased length of stay

●Conversion of donor site

PREVENTION — Early excision and skin grafting (days 1 to 5) reduces the presence of potentially necrotic and infected tissue and thereby reduces the risk of invasive and noninvasive burn wound infections [5,8]. Early excision of necrotic tissue and closure of the burn wound has been one of the single greatest advancements in the treatment of patients with severe thermal injuries and a mainstay of therapy [25-27]. (See "Overview of surgical procedures used in the management of burn injuries", section on 'Skin grafting' and "Hypermetabolic response to moderate-to-severe burn injury and management", section on 'Early excision and grafting'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Care of the patient with burn injury".)

SUMMARY AND RECOMMENDATIONS

●Burn wound infection – Infection remains the most common cause of morbidity and mortality in burn patients. Although the overall incidence of burn wound sepsis has declined, the incidence of burn wound infection among those with total body surface area (TBSA) burn >15 percent has remained approximately 6 percent. Patients with burn wounds also have high rates of other types of infection, such as catheter-related infection. (See 'Epidemiology and risk factors' above.)

●Risk factors – A variety of factors increase the risk of developing invasive burn wound infection (burn wound sepsis). Individuals who sustain a TBSA burn >20 percent are at particularly high risk; however, burn wound infection and sepsis can occur in smaller burns. Other factors include delays in burn wound excision, extremes in age (very old, very young), and impaired immunity. Microbial factors, such as type, virulence, and bacterial count (>10⁵ organisms per gram of tissue), increase the risk of an invasive wound infection. (See 'Risk factors' above.)

●Microbiology – The organisms that can colonize the burn wound and potentially give rise to burn wound infection vary with time and location (table 1). We routinely swab burn wounds for culture at the time of admission, weekly, and again if there are any concerning changes in appearance or the clinical condition of the patient. The most common organisms are Staphylococcus and Pseudomonas; however, the epidemiology of burn wound infections changes over time and also depends on the specific burn unit. A bacterial burden >10⁵ bacteria per gram of tissue results in impaired skin graft take and promotes systemic infection. (See 'Pathogenesis' above and 'Microbiology' above.)

●Clinical features – The recognition of burn wound infection remains challenging due to the many features unique to a burn injury. A rapid change in the clinical condition of the burn patient, such as increasing pain or changes in the gross appearance of a burn wound or skin graft donor sites, intolerance of enteral feedings, or systemic signs, is indicative of burn wound infection and potentially burn wound sepsis. (See 'Clinical features' above.)

●Diagnosis – When wound infection is suspected clinically based upon clinical features, quantitative wound cultures and examination of histopathology obtained by biopsying the wound are necessary to confirm the diagnosis of burn wound infection (>10⁵ bacteria per gram of tissue), which may or may not be invasive (algorithm 1). (See 'Diagnosis' above.)

•Most laboratory studies are nonspecific. Serum procalcitonin may differentiate bacterial infection from noninfective causes of fever; however, a specific cutoff value is difficult to define; trends may be more useful. (See 'Laboratory findings' above.)

•Criteria used for a diagnosis of sepsis in unburned patients often do not apply in burn patients, particularly severely burned patients, due to alterations of the patient's metabolic profile by inflammatory mediators. The burn sepsis definition distinguishes physiologic changes that occur secondary to the hypermetabolic response of the burn itself from those that result from microbial infection. Specific criteria have been suggested by the American Burn Association. (See 'American Burn Association criteria for burn wound sepsis' above.)

•For patients who have clinical changes and/or systemic signs concerning for burn wound infection or sepsis, we biopsy the burn wounds typically during the operative excision of any necrotic or infected tissue. (See 'Wound culture, tissue biopsy, and histopathology' above.)

●Categorization and treatment – The categories of burn wound infection are characterized based upon clinical features and depth of invasion. Depending upon the burn wound category, treatment of burn wound infection consists of a combination of burn wound care (ie, cleansing, dressings), topical antimicrobial therapy, systemic antimicrobial therapy, and burn wound debridement or excision. (See 'Burn wound categories' above and 'Treatment' above.)

•Noninvasive burn wound infection – Noninvasive burn wound infection is characterized by typical clinical features of burn wound infection without systemic signs, bacterial count >10⁵ bacteria per gram of tissue (or recovery of mold or yeast by culture), and no microbial invasion into unburned tissue. Treatment consists primarily of topical antimicrobial therapy and burn wound excision for unexcised wounds, and possibly reexcision for excised wounds. (See 'Noninvasive infection' above.)

•Invasive burn wound infection – Invasive burn wound infection is characterized by typical clinical features of burn wound infection and systemic signs, bacterial count >10⁵ bacteria per gram of tissue obtained from a burn wound or eschar, and microbial invasion into unburned tissue. Treatment is initiated with systemic broad-spectrum antimicrobial therapy and excision of all infected tissue to healthy tissue bed as determined by intraoperative biopsy. Specific antimicrobial therapy is guided by the results of burn wound culture and histopathology. (See 'Invasive infection' above.)