Burn Wound Colonization,Infection,and Sepsis

Abstract

Background:

Infection is a major cause of morbidity and mortality among burn patients, and it is important to understand the progression of wound colonization to wound infection to systemic sepsis.

Methods:

After a review of the literature we describe the clinical characteristics of burn wound colonization, infection, and sepsis, and conclude with best practices to decrease these complications.

Results:

Burn wounds are initially sterile after the thermal insult but become colonized by gram-positive organisms and subsequently by gram-negative organisms. Some populations are especially susceptible to initial or subsequent colonization by drug-resistant organisms. An increase in fungal colonization has been observed because of the widespread use of topical antibiotic agents. Male gender, older age, lower extremity burn, scald burn, full-thickness burn, delay in treatment, and pre-existing diabetes place patients at increased risk of infection. These infections range from cellulitis that requires systemic antibiotic agents, to invasive burn wound infection that requires prompt treatment with antibiotic agents and excision. Fungal wound infections pose a special challenge and cause substantial morbidity. Infection that leads to systemic sepsis is difficult to define in burn patients because of the body's compensatory hypermetabolic response to the burn injury. Potential sources of sepsis include wound infections and common nosocomial infections. The American Burn Association Sepsis criteria, defined in 2007, has demonstrated poor specificity for identifying sepsis and septic shock. The best approach to decrease wound infections is prevention. Practices that have been beneficial include isolation rooms, handwashing, appropriate wound care, early excision and grafting, antibiotic stewardship, and nutritional support.

Conclusions:

A burn patient remains at a substantial risk of wound infection despite advances in care. A burn care provider must understand the natural progression of colonization to infection to sepsis, and the multidisciplinary approach to wound care to limit the morbidity and mortality from these infectious.

Infection is a major cause of morbidity and mortality in hospitalized burn patients. The loss of the barrier function of the skin with the resultant moist burn wound bed results in an environment conducive to infection that may progress to systemic sepsis, shock, and death. This tendency of progression to systemic involvement may be increased in the host with an immunocompromised state secondary to increased age, large burn size, diabetes, or other comorbidities.

For a burn care provider, it is important to understand this natural progression from burn wound colonization to invasive burn wound infection to institute care focused at preventing or limiting the morbidity and mortality of this complication. In the following sections we describe the clinical characteristics of these infections and conclude with best practices to decrease infectious complications.

Burn Wound Colonization

A burn wound is initially sterile because the resident flora is killed by the thermal insult. After a superficial burn, resident flora surviving in hair follicles and sebaceous glands can lead to colonization of the burn wound, but the primary mode of colonization for burn wounds remains the environment and the patient's gut and nasopharyngeal tract. As a result of the nutrient-rich environment and reduced blood supply, a single bacterium can multiply into 10 million bacteria within 24 hours to colonize the entire wound. If left untreated, this rapid colonization can lead to infection [1].

The American Burn Association (ABA) Consensus Conference met in 2007 to standardize the definitions of infections and sepsis in burn patients. They defined wound colonization as low concentration of bacteria on the wound surface, absence of invasive infection, and less than 10⁵ bacteria per gram of tissue [2].

Burn wounds are initially colonized by gram-positive organisms, consistent with the normal resident flora of the skin, but over time gram-negative organisms begin to colonize the wound as well. Pseudomonas aeruginosa is the most common gram-negative organism that colonizes burn wounds. The production of glycocalyx, fimbriae, and many cell surface enzymes allow it to thrive in an aquatic environment of the burn wounds and medical devices in the burn units. Only present in 5% of burn wounds at the time of admission, Pseudomonas aeruginosa eventually colonizes over 70% of burn wounds. Depending on the burn center, more than 95% of Pseudomonas organisms may be resistant to multiple antibiotics [3]. In one study, the mean number of days from admission to identification of Pseudomonas in burn wounds was approximately 10 days, and the mean number of days from admission to identification of gentamicin-resistant Pseudomonas in burn wounds was 15 days [4].

Initial colonization with multiple-drug–resistant organisms (MDRO) may occur in patients with resident MDRO flora. Typically, this is seen in patients with facial burns who are carriers of nasal methicillin-resistant Staphylococcus aureus (MRSA) or in foot burns in patients with diabetes and pre-existing foot ulcers. Patients with chronic illnesses and repeated hospital exposures must also be suspected of carrying MDRO resident skin flora.

Acinetobacter calcoaceticus baumannii is another common gram-negative nosocomial organism that colonizes burn wounds. Colonization by this organism is associated with increased risk of infection, and colonization at the time of admission is associated with a more rapid onset of infection. Most of the isolates obtained from burn wounds in one study were resistant to a broad range of antibiotic agents [5].

The primary purpose of using topical antibiotic agents is to decrease the bacterial burden in the wound. However, many MDRO identified in burn wounds have some degree of resistance to common topical antibiotic agents used in contemporary burn care. This leaves the bacterial growth in burn wounds unchecked, which can lead to subsequent infection and possibly sepsis [6].

The loss of skin barrier, immunosuppression, and the use of topical antibacterial agents also creates an optimum environment for colonization of the burn wound by fungal organisms. Common organisms seen in the burn wound include Candida, Aspergillus, Fusarium, Mucor, and Rhizopus species. These organisms are ubiquitous in the environment and can be spread to burn wounds via hospital staff and the airborne route. However, Candida colonization of the burn wound appears to be primarily from endogenous sources [7,8]. Specific factors that can lead to colonization by Fusarium species include trauma caused by implantation of vegetable or soil matter and use of contact lenses [9].

Burn Wound Infection

Burn patients have a myriad of risk factors for infections after a thermal injury. Loss of the primary defense mechanism, skin, provides easy access to the wound and blood stream for pathogens. There is also an activation of the inflammatory cascade that results in the development of depressed cell-mediated and humoral immune functions, mediated by production of inflammatory agents by macrophages [4]. The magnitude of this immunosuppression correlates with the extent of the burn injury [7].

A national study that evaluated patients in the National Burn Repository over a 10-year period identified older age, male gender, lower extremity burns, scald burns, and full-thickness burns at higher risk of burn wound cellulitis. A delay in treatment, defined as seeking medical treatment more than 24 hours after injury, was associated with an eight times increased risk of cellulitis, whereas African American race was identified as being protective [10].

Pre-existing diabetes mellitus places burn patients at substantial risk for infectious complications. A single-center study of 68 patients with diabetes and lower extremity burns reported a 44% rate of infection in this group. These infections included cellulitis, osteomyelitis, and deep plantar infections [11]. A prospective study of more than 2,200 outpatient burn patients seen at our institution reported an overall infection rate of 5%, which increased to 15% in patients with diabetes, and to 62% in patients with diabetes with below the knee burns [12].

Diagnosis of burn wound infection can be complicated. Signs and symptoms such as pain, elevated temperature, and tachycardia are common after a burn injury as a result of the cytokine and immune responses to the thermal insult. Furthermore, not all wounds that appear erythematous are infected, and there is overlap between visible changes secondary to infection and changes secondary to the burn itself. An astute provider must be able to combine the subjective and objective findings to diagnose the presence and extent of the infection. Subjective findings include pain, erythema, odor, changes in wound color or depth, eschar separation, and systemic signs of infection. Some pathogens produce characteristic changes in the burn wound which can help point towards that particular pathogen, as described later. Objective findings include wound culture from swabs or tissue biopsies, described in one of three ways: qualitative (presence or absence of pathogen), semi-quantitative (grading of pathogen presence in wound as scant, few, moderate, or heavy), and quantitative (an absolute pathogen count) [1].

There are many different types of infections that can affect a burn wound, each with its own implications on the outcome of the wound and the patient.

Burn wound erythema

Burn wound infection must be differentiated from burn wound erythema. Initial erythema of the burn wound and the immediately surrounding skin is a sterile phenomenon caused by the release of inflammatory mediators from the tissues surrounding the burn. It typically presents within two to three days after the injury and resolves within a week. Unlike cellulitis, burn wound erythema lacks induration or tenderness and does not increase in area over time [1].

Cellulitis

Cellulitis is a non-invasive superficial infection of the burn wound and tissues surrounding the burn wound, and is characterized by edema, hyperesthesia, erythema, tenderness, and induration on examination [1]. The ABA defined this local wound infection as high concentration of bacteria in the wound or wound eschar, absence of invasive infection, and greater than 10⁵ bacteria per gram of tissue [2].

Early cellulitis is typically caused by the patient's resident skin flora and is pan-sensitive unless the patient is an MDRO carrier. At approximately seven to 10 days post-burn, gram-negative organisms such as Pseudomonas become a more common source of infection. This transition classically presents with a yellow-green color change of the wound and a fruity odor, caused by the production of pyocyanin compounds [1,3].

Impetigo (melting graft-wound syndrome)

Impetigo is a wound infection that typically occurs in patients with facial burns who are nasal carriers of Staphylococcus aureus, usually MRSA. It presents with a crusting exudate on the upper lip that then spreads to surrounding burned facial skin. There is minimal surrounding erythema of surrounding uninvolved skin.

Impetigo may also occur as the melting graft-wound syndrome. This is a wound infection that can occur after spontaneous closure of a partial thickness wound or donor site. There is loss of healed skin with minimal erythema or exudate and the skin loss is commonly initially attributed to superficial trauma, such as scratching of the healed site. The diagnosis is clinical but can be confirmed via a wound culture. The most common organism responsible for this infection is MRSA, although Proteus, Candida, and Acinetobacter may also be the cause [1,13].

Invasive Burn Wound Infection

An invasive burn wound infection is characterized by change in color, exudative drainage, and odor from the wound, with or without systemic sepsis. It leads to conversion of partial-thickness wound to full-thickness, and expansion into surrounding unburned tissues [1]. The ABA defined an invasive wound infection as greater than 10⁵ pathogen per gram of tissue present in the wound, invasion or destruction of unburned skin/tissue, and presence or absence of sepsis [2]. Diagnosis is usually based on clinical examination and quantitative culture but can be confirmed via histologic examination of the tissue, which is considered the gold standard [1]. Systemic antibiotic therapy is typically insufficient to obtain source control, especially if the infection involves full thickness burn eschar, and excision at the time of diagnosis is necessary.

Ecthyma gangrenosum is an invasive burn wound infection caused by Pseudomonas aeruginosa. It presents with purple-blue “punched-out” lesions in the skin and often causes local thrombosis of the blood vessels [1,3]. Unless treated promptly with appropriate antibiotic agents and excision of the infected soft tissue, it can progress rapidly to systemic sepsis, shock, and possibly death.

Fungal burn wound infection

The widespread use of broad-spectrum antibacterial topical agents in burn patients has resulted in an increase in fungal burn wound colonization. Candida colonization is common and may inhibit epithelialization of the wound. Resistant Candida species are becoming more common and systemic antifungals should be based on wound cultures. Addition of nystatin to topical wound care can assist in control of the yeast. Invasive Candida infection is rare and candidemia should be considered secondary to venous catheter infection and treated accordingly. Candida must also be considered in cases in which healed grafts and donor sites begin to break down.

Aspergillus is ubiquitous in our environment. Infections typically occur in immunocompromised patients with large burn size and delay in definitive wounds closure. Treatment consists of aggressive wound debridement and closure with administration of voriconazole.

Mold infections from Mucor, Rhizopus, and Fusarium may be seen in patients immunocompromised by large burns or comorbidities such as poorly controlled diabetes. Typically, the patient is clinically unstable with a large burn that has remained open for a prolonged period of time. Treatment involves aggressive debridement that may require amputation of involved limbs. Voriconizole or liposomal amphotericin may be administered, but overall prognosis is poor.

Burn Sepsis

Sepsis is difficult to define in burn patients because of the compensatory hypermetabolic response to the burn injury. This renders the traditional criteria established by the Society of Critical Care Medicine impractical in this patient population. The ABA Consensus Conference met in 2007 to address this problem. They defined sepsis as “a change in the burn patient that triggers the concern for infection” and identified triggers that must be tied to the discovery of an infection (Table 1). This can progress to septic shock that was defined by ABA as “persistent hypotension despite adequate fluid resuscitation and/or lactate >4 mmol (36 mg/dL)” [2]. Risk factors associated with sepsis and increased mortality include high concentrations of bacteria in the burn wound, delayed presentation to a burn center, delayed removal of burned tissues, and decreased lean body mass [1]. Studies have shown that ABA Sepsis Criteria correlates poorly with the development of bacteremia in critically ill burn patients [14,15]. To date, no criteria or scoring system has demonstrated good specificity for identifying sepsis in burn patients.

Table 1.

American Burn Association Consensus Definition of Sepsis in Burn Patients [2]

Trigger and documented infection
The trigger includes at least three of the following:
1. Temperature >39°C or <36.5°C
2. Progressive tachycardia
a. Adults >110 bpm
b. Children >2 SD above age-specific norms (85% age-adjusted maximum heart rate)
3. Progressive tachypnea
a. Adults >25 bpm not ventilated, or minute ventilation >12 L/min ventilated
b. Children >2 SD above age-specific norms (85% age-adjusted maximum respiratory rate)
4. Thrombocytopenia (will not apply until 3 days after initial resuscitation)
a. Adults <100,000 /mcL
b. Children <2 SD below age-specific norms
5. Hyperglycemia (in the absence of pre-existing diabetes mellitus)
a. Untreated plasma glucose >200 mg/dL or equivalent mM/L
b. Insulin resistance—examples include:
i. >7 units of insulin per hour intravenous drip (adults)
ii. Significant resistance to insulin (>25% increase in insulin requirements over 24 hours)
6. Inability to continue enteral feedings >24 hours
a. Abdominal distension
b. Enteral feeding intolerance (residual >150 mL/h in children or two times feeding rate in adults)
c. Uncontrollable diarrhea (>2500 mL/d for adults or >400 mL/d for children)
In addition, it is required that a documented infection is identified:
1. Culture positive infection, or
2. Pathologic tissue source identified, or
3. Clinical response to antimicrobials

SD = standard deviation; bpm = beats per minute.

Burn wound infection is only one of several sources of sepsis and septic shock in critically ill burn patients. These patients are also at risk of common nosocomial infections such as ventilator-associated pneumonia, central line-associated blood stream infections, and catheter-associated urinary tract infections. The incidence, diagnosis, and treatment of these nosocomial sources of sepsis and septic shock in burn patients is discussed elsewhere.

Special Considerations

Chondritis

The skin overlying the pinna is thin and underlying cartilage is at risk for infection. Chondritis presents with edema of the ear that results in protrusion of the pinna from the head. The ear will be extremely tender to palpation. Prevention consists of application of mafenide acetate cream that is well absorbed and obtains antibacterial minimum inhibitory concentration in the cartilage. Treatment of active chondritis includes bi-valving the ear, removal of involved cartilage and packing with mafenide. Appropriate broad-spectrum antibiotic agents are indicated and tailored by operative cultures.

Diabetic foot infections

As noted earlier, patients with diabetes have an increased risk of burn wound infection. A patient with pre-existing ulcerations of the foot is at increased risk of infections with MDRO. Blood sugar levels should be controlled appropriately especially in the patient with large burn size. Lower extremity burns are at substantial risk of infection. Evaluation of the burned lower extremity must include a vascular examination, and the combination of diabetes with peripheral vascular disease places the patient at substantial risk of burn wound conversion to full-thickness degree and infection.

For patients with diabetes, small partial thickness burns may be treated in the outpatient setting. Prophylactic antibiotic agents do not decrease the incidence of infection and merely select out MDRO. If outpatient therapy is selected, it is prudent to have the patient return in 48 to 72 hours to evaluate for a burn infection.

Combined trauma and burn patients

In this patient population, it may be necessary to make incisions through burned skin. If the burn is full thickness, the skin around the incision should be removed at the time of the initial operation and the wound either grafted on left open with appropriate topical antibiotic agents. If left open, the wound should be considered for early grafting. Consideration should be given to initial external fixation of long-bone fractures, but again it is prudent to excise full-thickness burns around incisions with consideration of immediate or early grafting. Delay in operative fixation of fractures merely results in an operation in a heavily colonized patient and increase in wound infection.

Best Practices to Decrease Burn Wound Infections

The best approach to burn wound infection is clearly to prevent its occurrence. As outpatient burn care becomes more common for burns of moderate size, it is necessary to evaluate the patient's care plan to ensure that these practices can be reasonably obtained in the outpatient setting. In this section, advances in the prevention of infection in the burn patient will be summarized.

Environment

Although early colonization of the wound is derived from the patient's endogenous skin flora, later colonization is caused by contamination with organisms from the environment. Large burns are more susceptible to infection and should be isolated in single rooms. Handwashing is essential. Caregivers should minimize the risk of cross-contamination of patients using gloves, gowns, and masks when providing wound care; some units require this gear for any person entering the patient's room. Common areas of the units are potential sources of cross-contamination and all dressing tables, hydrotherapy units, and therapy equipment must be decontaminated thoroughly between use. Patients infected with MDRO should have dedicated dressing tables and therapy equipment. Nothing should be removed from the room of a patient colonized or infected with MDRO without through decontamination, including the use of ultraviolet units.

Water is commonly contaminated with Pseudomonas. Hydrotherapy units, faucets, and other water sources should be cultured routinely for Pseudomonas and MDRO and decontamination may be necessary if these organisms are found.

Dressing care

Burn wounds should be cleaned with removal of loose superficial skin at initial presentation. Patients with small, superficial partial-thickness burns who are candidates for treatment as outpatients may be dressed with topical antibiotic agents and the patient and family instructed in wound care. Alternatively, a silver-based product may be placed for a longer period of time with dressing changes at the time of follow-up appointment.

Patients with more substantial burns should be admitted with daily wound inspection and dressings until the risk of wound infection is minimized. The role of routine scheduled wound cultures remains controversial but any suspicious burns should be immediately cultured.

Early excision and grafting

The introduction of early burn excision and grafting has made the greatest contribution to the reduction of burn wound infection and death. The excision of full-thickness burns to a clear, well-vascularized bed with immediate grafting remains the standard of care. Unfortunately, many patients with large burns are too unstable for the stress of a large burn excision and grafting and its resultant blood loss. The goal should remain early excision of all full-thickness burns as soon as possible with staged autografting. Allograft of other artificial skin substitutes may be utilized until donor sites heal for repeat harvesting.

Antibiotic stewardship

Prophylactic systemic antibiotics are clearly contraindicated at the time of burn presentation. The burn wound is poorly perfused, and any full-thickness eschar is not perfused at all. Systemic antibiotic agents do not achieve substantial tissue levels in the burned tissue and merely select out resistant organisms from the myriad of bacteria colonizing the wound. If antibiotic agents are later indicated for the treatment of wound infection, dosage should take into consideration the increased metabolism of the critically burned patient.

Nutrition

Adequate nutritional support for the critically burned patient is essential for burn wound treatment. Patients with baseline malnutrition such as the elderly, homeless, morbidly obese, and patients with substance abuse are at increased risk of burn wound infection. The increase in skin colonization and the common occurrence of MDRO makes central line infections more common and parenteral nutrition more risky than for the typical critically ill patient. Active infection exacerbates the baseline hypermetabolism of the burn patient and complicates the delivery of adequate nutrition.

Conclusions

The burn patient remains at a substantial risk of burn wound infection despite the advances in wound care, topical and systemic antibiotics, and early excision and grafting of the wound. The atypical appearance of the burn wound and the systemic inflammatory response to burn injury complicates the early diagnosis of burn wound infection. Therefore, a multidisciplinary approach to burn wound care to reduce the incidence of burn wound infection with associated attention to the wound to make early diagnosis possible are necessary to prevent burn wound infection to progressing to sepsis, shock, and death.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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