Burn Infection and Burn Sepsis

Abstract

Background:

Infection is the most common complication and cause of death in patients suffering burn injuries. These patients are susceptible to infection and burn wound sepsis secondary to the alterations in their physiology. Diagnosis and management of infections rely on physical examination, cultures, and the pathology of the burn wound.

Method:

We performed an electronic search for articles in the Google Scholar and PubMed databases using the search terms “burn sepsis,” “burn infection,” and “burn critical care.”

Results:

Multiple factors increase burn patients' risk of invasive infection and sepsis, including underlying factors and co-morbidities, the percent total body surface area of the burn, delays in burn wound excision, and microbial virulence/bacterial count. Organisms causing burn wound infection differ, depending on the time since injury and its location; and diagnosis is multi-factorial. The most common pathogens remain Staphylococcus and Pseudomonas spp.

Conclusion:

Overall, the recognition of burn sepsis is based on clinical findings. Treatment consists of a combination of local dressings, early burn excision, and systemic antimicrobial therapy. The mortality rate has decreased significantly over the past 10 years, but continued efforts at timely management and infection prevention are essential.

Infection is the most common complication and cause of death in patients suffering burn injuries because of the multiple alterations in their physiology. The most common pathogens are Staphylococcus and Pseudomonas spp.

The diagnosis and management of infections in burn patients rely on physical examination, cultures, and the pathology of the wound Treatment should be targeted at the organisms based on the temporal relations to time of admission and specific to those prevalent in the burn unit based on respective antibiograms. Special systemic considerations also are important in these patients, as they often are prone to infection secondary to invasive procedures required for the management of the wound, such as endotracheal tubes, urinary catheters, and central venous lines. Both local and systemic therapies, as well as universal infection prevention strategies, are essential in the management of infection and reducing organism transmission.

Epidemiology and Risk Factors

In 2016 in the United States, approximately 486,000 people sustained burn injuries [1]. These injuries do not always necessitate hospital admission, but approximately 40,000 patients require medical attention; and 75% require burn specialist care. In Canadian-based studies assessing the burden of major burns in the province of Ontario, it was found that the number of patients treated at a regional burn center increased from 57% to 71%. Therefore, nearly 30% of patients with large, major burns receive care outside specialized centers [2]. Overall, the incidence and severity of burn injury, including burn extent and inhalation injury, have remained stable over time.

Infection is the most common complication faced by patients with burn injuries. The infecting organisms are not confined to one anatomic location; they can be involved in infections of the surgical wound as well as systemically. The most common sites for surgical burn wound infection are in the lower extremities. However, patient admissions frequently are complicated by pneumonia, urinary tract infection (UTI), and cellulitis [1]. Factors that may contribute to respiratory infections include the presence of inhalation injury and the need for prolonged mechanical ventilation. In those sustaining fire/flame burns, pneumonia occurred in 5.4% of patients and UTI in 3.4% [1]. Generally, the risk of UTI is associated with the use of urinary catheters and prolonged hospitalization.

Initial rates of burn wound sepsis were estimated at 6% [3]. However, these infections have decreased significantly since the advent of early burn wound excision and now are approximately 1% [4]. In patients with large percentage total body surface area (%TBSA) burns (> 15%), the rates have remained largely unchanged.

Pathogenesis and Microbiology

Common pathogens

Burn injury predisposes patients to infection by both local and systemic factors because of the burn's effect on metabolic and immunologic host defenses [5,6]. The bacteria responsible for infection manifest chronologically, changing depending on the time since the initial burn. By far the most common pathogen involved in burn infection remains Staphylococcus aureus [7].

Given that burn patients have lost their primary protective barrier (skin), they are susceptible to colonization by both endogenous and exogenous micro-organisms (Table 1). The burn eschar provides an environment conducive to bacterial growth because of its protein richness, release of toxic substances, and avascularity, which impedes the delivery of antimicrobial drugs [8,9].

Table 1.

Common Burn Wound Pathogens

Organism	Common species	Common time of presentation
Gram-positive bacteria	Staphylococcus spp.	Common at all phases
Gram-positive bacteria	Streptococcus spp.
Gram-negative bacteria	Pseudomonas aeruginosa	>5 d
	Acinetobacter baumannii
	Escherichia coli	<5 d
	Klebsiella pneumoniae	<5 d
	Enterobacter cloacae
Yeast	Candida species	7–14 d
Fungi	Aspergillus, Penicillium, Rhizopus, Mucor, Rhizomucor, Fusarium, Curvularia	7–14 d
Virus	Herpes simplex virus; cytomegalovirus

Timeline of infection

In the first five days post-burn (early phase), the most common pathogens are gram-positive, whereas gram-negative bacteria increase in prevalence after five days (late phase) [10]. The most common pathogens in the early phase are S. aureus, Haemophilus influenzae, Escherichia coli, and Klebsiella. The most common late-phase pathogens include S. aureus and Pseudomonas aeruginosa. Yeast and fungal infections typically occur later, around 7–14 days post-burn, followed by multi-drug–resistant (MDR) infections (Table 1).

Fungal infections

Fungal infections are complicated by delay in identification because of a systemic presentation similar to that of bacterial infections [11]. However, their wound appearance is quite specific and includes black eschar and early separation of the eschar. Risk factors for fungal infections are large %TBSA, multiple operations, use of broad-spectrum antibiotics, prolonged stay, impaired immune defenses, use of central venous catheters, and parenteral nutrition [12]. They are not restricted to the burn wound and may occur systemically. Overall, the incidence of fungal infections has increased with the use of topical agents and empiric broad-spectrum antibiotics and has been linked to a higher mortality rate [13].

Multi-drug–resistant bacteria

There are several risk factors for MDR bacteria, including hospital length of stay [14,15], previous antimicrobial therapy, inadequate burn excision, and use of invasive medical devices [16 –18]. Diagnosis can be difficult, as colonization usually precedes infection. Because of empiric therapy with broad-spectrum antibiotics during the initial burn treatment, resistance patterns and sensitivities have been changing [16,17]. Pathogens of particular concern are MDR strains of P. aeruginosa, Stenotrophomonas maltophilia, Acinetobacter, and methicillin-resistant S. aureus (MRSA). There also have been reported burn unit outbreaks of carbapenem-resistant Enterobacteriaceae [19].

Special Systemic Considerations

Catheter-related infections

Use of intravenous (IV) and intra-arterial catheters are commonplace in burn patients to provide access for fluid resuscitation, parenteral nutrition, and administration of medications. However, despite their value, they increase the risk of central line-associated blood stream infection (CLABSI). Host factors such as immunodeficiency, malnutrition, older age, previous blood stream infection (BSI), and chronic illness commonly are associated with CLABSI. In burn patients specifically, the loss of skin integrity and insertion of catheters through burnt tissue can result in migration of contaminants to the catheter tip [20]. The thermal injury itself decreases host resistance and increases the body's natural inflammatory response [21]. Important extrinsic factors associated with an increased risk of infection are the duration of catheterization, conditions of catheterization, material of the catheter, catheter-site care, and the skill of the inserter [22]. The location of the insertion also can confer greater risk, specifically lines inserted in the lower extremities. The most common hospital-acquired infection is blood stream infection (39.2% cumulative, 8.7% of all burn patients) [23]. Some studies found that CLABSI is one of the most common hospital-acquired infections in patients with moderate to severe burns, with a mean of 4.8 per 1,000 central line days [23]. Minimizing CLABSI rates can be achieved through appropriate use of hand hygiene, sterile technique on insertion, use of 2% chlorhexidine solution prior to insertion, avoiding femoral sites when possible, and prompt removal of unnecessary catheters [24].

Catheter-associated urinary tract infection (CAUTI) also may complicate burn admissions, as urinary catheters often are used in monitoring the effectiveness of fluid resuscitation and the patient's renal function. Bacteriuria occurs in patients with urinary catheters at a rate of approximately 3%–10% per day of catheterization, with 10%–25% of colonizations progressing to symptomatic UTI [25]. One of the most important risk factors for CAUTI and a primary target for prevention is the duration of catheterization [26]. Other risk factors include older age, being female, diabetes mellitus, improper catheter care or insertion, and bacterial colonization (biofilm, urinary stasis, or collection bag contamination) [25].

Blood stream infections

The presence of BSI and sepsis in burn patients increases the mortality rate four-fold [27]. Early use of broad-spectrum antibiotics, need for fasciotomy/escharotomy, and larger %TBSA increase the risk of invasive nosocomial and fungal infections, particularly with MDR bacteria [28 –30]. Both Candida spp. and MDR bacteria are suggested to cause late BSI [31] with a median intensive care unit (ICU) stay of 16–26 days [28]. The most common BSI pathogens are Enterococcus spp., Pseudomonas spp., and Candida spp.

Genitourinary infections

Although prolonged urinary catheterization is the primary cause of genitourinary infections, bacterial and fungal translocation from the blood stream also may be a source [10]. Asymptomatic bacteriuria in an ICU population leads to excessive testing and inappropriate antimicrobial treatment.

Respiratory infections

Hospital-acquired pneumonia (HAP) is one of the most common hospital-acquired infections and occurs in nonventilated patients [32]. However, the patients most at risk are those on mechanical ventilation, developing ventilator-associated pneumonia (VAP) within 48 hours after intubation.

Gastrointestinal infections

Because of the profound inflammatory response post-burn, there may be significant loss of gut barrier function and translocation of enteric bacteria into mesenteric lymph nodes leading to blood stream and respiratory infections [33,34]. Common opportunistic bacteria are Klebsiella, Proteus, Escherichia, and Citrobacter. Greater than 90% of ICU patients with infection had at least one episode with organisms identified in the upper gastrointestinal tract [35]. Clostridioides difficile is an important opportunistic pathogen that affects those who are treated with antibiotics, are immunocompromised, or have been infected previously.

Clinical Diagnosis

Wound appearance

Burn wound infections typically are assessed clinically by their overall appearance and the patient's systemic status. Changes in the appearance of the wound, including conversion of partial-thickness to full-thickness injury or loss of a previously viable skin graft, may suggest an acute infection. This typically presents as some combination of pain, purulence, edema, malodour, or discoloration of the skin graft or donor site. Cellulitis of surrounding uninjured skin also may occur. Fungal infections characteristically result in rapid separation of the eschar with central ischemic necrosis and spread of subcutaneous edema [36].

Invasive burn wound infection or burn wound sepsis is most reliably identified by conversion of partial- to full-thickness injury or necrosis of previously healthy tissue. This may appear as discoloration (brown, black, violaceous) or sloughing of a prior viable graft [36]. Other findings suggestive of invasive burn wound infection are hemorrhagic staining of sub-eschar tissue, edema or violaceous discoloration of the burn margin, burn eschar separation, green pigmentation in fat (pyocyanin; indicative of Pseudomonas), erythematous or black necrotic nodular lesions in uninjured skin (ecthyma gangrenosa), or exophthalmos (mucormycosis and retrobulbar involvement in midface burns) [9,36,37].

Systemic alterations and laboratory abnormalities

Like patients with other systemic signs of sepsis, burn patients may present with tachycardia, hypotension, tachypnea, altered mental status, oliguria, hyperglycemia, and thrombocytopenia. Leukocytosis may be present but is not an accurate indicator of sepsis, as all severely burned patients have elevated white blood cell (WBC) counts because of the loss of the primary skin barrier [38]. There also are multiple protein biomarkers in burn sepsis, some of which include acute-phase reactants (C-reactive protein/erythrocyte sedimentation rate, procalcitonin), anticoagulant factors (antithrombin, protein C), cytokines (interleukin [IL]-6, IL-10, IL-13, IL-18, IL-27, tumor necrosis factor-α), and tissue injury biomarkers (serum lactate) [39]. Procalcitonin is secreted in response to severe bacterial infections, sepsis, and multi-organ dysfunction; it has high sensitivity (74%–77%) and specificity (65%–88%) in identifying sepsis in burn patients [40,41]. There should be a high clinical suspicion of sepsis in patients with a procalcitonin concentration of 1.5 ng/mL [40]. A concentration of >3.66 ng/mL may be a marker of poor outcome in these patients [42].

Wound cultures and tissue biopsy

Surface wound swabs may help identify the predominant bacteria and can be used as surveillance if there is any clinical concern about changes in the wound. However, a more reliable method of diagnosis is evaluating a burn wound with histopathology examination (staining and microscopic assessment of bacterial presence) and quantitative microbiologic assessment (absolute quantity of bacteria per unit of volume). Samples can be taken from multiple sites of concern. The diagnosis of infection can be made by assessing bacterial counts. Concentrations of <10⁵ organisms per gram of tissue suggest bacterial colonization of a wound, which does not necessarily impact healing. However, formation of a biofilm (complex polysaccharide matrices excreted by bacteria) can impact wound healing negatively by impairing antimicrobial treatment and ultimately lead to persistent colonization and a higher risk of systemic infection [43,44]. A sample measuring >10⁵ organisms per gram of tissue is the accepted threshold to define infection. Non-invasive infections present with clinical features of wound infection without systemic alterations, whereas invasive infections present with systemic signs and invasion into healthy tissue. Overall, the use of quantitative microbiology techniques is controversial. Limited evidence suggests that more than one sample should be analyzed, that biopsies may be more sensitive in predicting or diagnosing sepsis than swabs, that poor clinical outcomes may be associated with higher bacterial loads, and that results must be interpreted in conjunction with the clinical context [45].

A high bacterial load is a known factor in delayed wound healing. New non-invasive methods of detection use the principal endogenous autofluorescence to examine wounds and bacterial burden at the point of care. The Portable Real-time Optical Detection Identification and Guide for Intervention (PRODIGI) detects 85% of wounds with clinically significant bacterial loads that are missed by conventional testing methods [46].

Burn sepsis

Septic shock is defined as hyperdynamic cardiovascular instability resulting in organ hypoperfusion. Burn patients have increased susceptibility to infection and sepsis with three main criteria that aid in the diagnosis of burn sepsis: American Burn Association (ABA) [38], Mann-Salinas [47], and Sepsis-3 [48] (Table 2). Recent studies have identified the Sepsis-3 criteria as the most reliable assessment in burn patients, as it outperformed the other two criteria [49,50]. Overall, in a burn patient with suspected underlying infection, the most predictive clinical markers for burn sepsis were altered mental status (Glasgow Coma Scale <13), hyperthermia, increased oxygen requirements, and progressive tachycardia.

Table 2.

Sepsis Criteria in Burns [49]

ABA	Mann-Salinas	Sepsis-3
Three or more of the following:1. Temperature >39° or <36.5°C2. Progressive tachycardia (> 110 bpm)3. Progressive tachypnea (> 25 bpm or >12L/min ventilated)4. Thrombocytopenia5. Hyperglycemia6. Inability to tolerate enteral feeding >24 h	• Tachycardia >130 bpm• MAP <60 mm Hg• Base deficit < -6 mEq/L• Hypothermia <36°C• Use of vasoactive drugs• Hyperglycemia >150 mg/dL• Tachycardia >130 bpm	qSOFA Score Suspected or documented infection and qSOFA ≥2 and/or SOFA ≥2: 1. Altered mental status (GCS <13) 2. Systolic blood pressure ≤100 mm Hg 3. Ventilatory rate ≥22 bpmSOFA variables • PaO₂/FiO₂ ratio • Glasgow coma scale • Mean arterial pressure • Vasopressor requirements • Serum creatinine or urine output • Bilirubin • Platelet countSeptic shock • Vasopressors required to maintain MAP >65 mm Hg • Serum lactate >2 mmol/L (after fluid resuscitation)

ABS = American Burn Association; bpm = beats/min; GCS = Glasgow Coma Scale; MAP = mean arterial pressure; SOFA = sequential organ failure assessment.

Management

Local

Topical antimicrobial drugs/antiseptic therapy

Local wound management involves cleansing, debridement, topical antimicrobial agents, and dressings, which are chosen on the basis of the suspected microorganisms. This may decrease the bacterial burden initially for unexcised burn wounds that are being managed conservatively or awaiting definitive excision. Excised burn wound tissue also may become infected, necessitating topical therapy.

In partial-thickness burns, commonly used topical agents are antimicrobial ointments (bacitracin/polymyxin B), silver-containing agents (silver sulfadiazine, Acticoat, Aquacel Ag), mafenide, acetic acid (0.5%–5%), Daikin's solution (≤ 0.5% sodium hypochlorite), and povidone–iodine. Other agents such as honey and bismuth-impregnated petroleum gauze also are used (Table 3) [10].

Table 3.

Common Topical Antimicrobial Agents

Agent	Targeted pathogens
Daikin's solution (0.5% sodium hypochlorite)	Gram-positive, gram-negative, yeast, fungi
Acetic acid (0.5%-5%)	Gram-positive, gram-negative, Pseudomonas (at higher concentrations)
Povidone–iodine	Gram-positive, gram-negative, fungi, viruses
Silver sulfadiazine	Gram-positive, gram-negative, yeast
Mafenide acetate (5%)	Gram-positive, gram-negative
Acticoat	Gram-positive, gram-negative, yeast, fungi, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus

Early surgical excision

The primary treatment for deep burn wounds is surgical excision, as it removes necrotic and possibly infected tissue [51]. Once the patient is stabilized and adequately resuscitated, wide excision of infected or burnt tissue is performed, preferably within the first 24 to 72 hours after the burn. Intra-operative samples are taken and can help guide antibiotic selection. Wounds often are reassessed at 24 to 48 hours and debrided again if there is any evidence of further non-viable tissue. Once the wound bed is deemed viable, it can be covered with a temporary skin substitute (i.e., allograft) or permanent autograft. The optimal timing for burn wound closure is five days. Early closure has been associated with decreased hypertrophic scarring, stiffness, and joint contractures and encourages faster rehabilitation [52,53]. However, this may pose a challenge for large %TBSA burns, where excision and autografting may be delayed or staged because of a lack of available donor sites.

Systemic

Antimicrobial prophylaxis

In patients with suspected burn sepsis, empiric broad-spectrum antibiotics are initiated concurrently with resuscitation. The choice of antibiotic is dependent on antibiograms of the individual institution and the most likely pathogens given the time since initial injury. In general, during the early phase of injury (< 5 days), an empiric regimen of ceftriaxone 1 g intravenously (IV) q 24 h ± cloxacillin 1–2 g IV q 4–6 h. In the late phase (> 5 days), antibiotics should include piperacillin-tazobactam 4.5 g IV q 6 h or meropenem 500 mg IV q 6 h + vancomycin 1 g IV q 12 h [10]. Whenever possible, antimicrobial drug choices should be based on isolates from wound, blood, or urine cultures. If a yeast species is suspected, treatment with fluconazole, amphotericin, or caspofungin should be initiated. Suspected viral infections should be treated with acyclovir. Resistant organisms, such as MRSA, vancomycin-resistant Enterococcus, carbapenem-resistant Enterobacteriaceae, carbapenemase-positive Klebsiella pneumoniae, MDR Acinetobacter, or MDR Pseudomonas, also require consideration and targeted therapy.

Sepsis resuscitation

For septic patients, initial management strategies are targeted at restoring end-organ perfusion. Immediate evaluation of airway, breathing, and circulation should be performed, while ensuring adequate intravenous access and early administration of fluids and antibiotics [54,55]. Crystalloids are the fluid of choice for resuscitation. The Saline versus Albumin Fluid Evaluation (SAFE) trial in critically ill patients demonstrated no benefit to albumin compared with saline [56]. In a burn meta-analysis, there was no benefit of albumin on the mortality rate; however, patients receiving albumin did require less fluid [57].

Identifying and controlling the source of infection is the most valuable therapy. Initial investigations should include a complete blood count, chemistry assays, liver function tests, coagulation studies, cardiac markers, serum lactate, arterial blood gas analysis, and peripheral blood cultures. Other targeted investigations may be warranted based on clinical suspicion of infection source (i.e., chest radiography, computed tomography of the chest or abdomen or both, urinalysis, wound/tissue cultures). Response to resuscitation should be monitored with central venous pressure, urinary output, hemodynamic status, lactate clearance, and normalization of base deficit. Patients who fail initial therapy may require vasopressors to ensure adequate perfusion. De-escalation of supports and antimicrobial drugs must be reassessed daily.

Morbidity and Death

Every year, there are roughly 3,400 burn-related deaths [1]. Sepsis and subsequent invasive infections continue to be the primary cause of death after the first 24 hours from initial burn injury. If the patient survives the first 24 hours of resuscitation, he or she may still deteriorate clinically over the following two weeks, leading ultimately to death.

Over the past 20 years, the mortality rate after burn injuries has declined substantially whereby the majority of burn injuries now are survivable [58,59]. Data from the province of Ontario suggest an improvement in the 30-day mortality rate over the past 10 years, particularly over the last three years [2]. At non-burn centers, the mortality rate varied.

Prevention

Universal infection prevention strategies are essential in improving transmission and outcomes of burn patients. Because of the long stay and frequent invasive procedures, burn patients are at greater risk of nosocomial infection. Common evidence-based strategies include hand hygiene, use of personal protective equipment, contact isolation, negative-pressure patient rooms, frequent room cleaning, daily evaluation of invasive lines and devices, burn unit antibiograms, use of topical antimicrobial agents, and involvement of antimicrobial stewardship programs [60 –62]. As previously discussed, early surgical excision (within the first five days after burn injury) reduces the risk of infection and sepsis significantly [38].

Conclusions

Infection continues to be one of the most common causes of morbidity and death in individuals sustaining burn injuries. There are multiple factors that increase patients' risk of invasive burn infection and sepsis, including underlying patient factors and co-morbidities, %TBSA, delays in burn wound excision, and microbial virulence/bacterial count. Organisms causing burn wound infection differ depending on the time since injury and location, and diagnosis is multi-factorial. Overall, the recognition of burn sepsis is based on clinical findings. Treatment consists of a combination of local dressings, early burn excision, and systemic antimicrobial therapy. The mortality rate has decreased significantly over the past 10 years, but continued efforts at timely management and infection prevention are essential.

Footnotes

Author Disclosure Statement

The authors have no conflicts of interest to declare.

References

American Burn Association. National Burn Repository 2016 Report. Chicago, IL: American Burn Association, 2016.

Mason

, Nathens

, Byrne

, et al. Trends in the epidemiology of major burn injury among hospitalized patients: A population-based analysis. J Trauma Acute Care Surg, 2017; 83:867–874.

Sørensen

, Fisker

, Steensen

, Kalaja

. Acute excision or exposure treatment? Final results of a three-year randomized controlled clinical trial. Scand J Plast Reconstr Surg, 1984; 18:87–93.

Herndon

, Barrow

, Rutan

, et al. A comparison of conservative versus early excision: Therapies in severely burned patients. Ann Surg, 1989; 209:547–552.

Alexander

. Mechanism of immunologic suppression in burn injury. J Trauma, 1990; 30(12 Suppl):S70–S75.

Heideman

, Bengtsson

. The immunologic response to thermal injury. World J Surg, 1992; 16:53–56.

Edwards-Jones

, Greenwood

, Group

MBR

. What's new in burn microbiology? James Laing Memorial Prize Essay 2000. Burns, 2003; 29:15–24.

Barret

, Herndon

. Effects of burn wound excision on bacterial colonization and invasion. Plast Reconstr Surg, 2003; 111:744–750.

Church

, Elsayed

, Reid

, et al. Burn wound infections. Clin Microbiol Rev, 2006; 19:403–434.

10.

Jeschke

, Shahrokhi

, Editors. Burn Care and Treatment. New York, NY: Springer, 2013.

11.

Becker

, Cioffi

, McManus

, et al. Fungal burn wound infection: A 10-year experience. Arch Surg, 1991; 126:44–48.

12.

Struck

, Gille

. Fungal infections in burns: A comprehensive review. Ann Burns Fire Disasters, 2013; 26:147–153.

13.

Horvath

, Murray

, Vaughan

, et al. Fungal wound infection (not colonization) is independently associated with mortality in burn patients. Ann Surg, 2007; 245:978–985.

14.

van Duin

, Strassle

, DiBiase

, et al. Timeline of health care-associated infections and pathogens after burn injuries. Am J Infect Control, 2016; 44:1511–1516.

15.

Wanis

, Walker

SAN

, Daneman

, et al. Impact of hospital length of stay on the distribution of gram negative bacteria and likelihood of isolating a resistant organism in a Canadian burn center. Burns, 2016; 42:104–111.

16.

Cavalcante

ReS

, Canet

, Fortaleza

. Risk factors for the acquisition of imipenem-resistant Acinetobacter baumannii in a burn unit: An appraisal of the effect of colonization pressure. Scand J Infect Dis, 2014; 46:593–598.

17.

Wibbenmeyer

, Williams

, Ward

, et al. Risk factors for acquiring vancomycin-resistant Enterococcus and methicillin-resistant Staphylococcus aureus on a burn surgery step-down unit. J Burn Care Res, 2010; 31:269–279.

18.

Guggenheim

, Zbinden

, Handschin

, et al. Changes in bacterial isolates from burn wounds and their antibiograms: A 20-year study (1986–2005). Burns, 2009; 35:553–560.

19.

Kanamori

, Parobek

, Juliano

, et al. A prolonged outbreak of KPC-3-producing Enterobacter cloacae and Klebsiella pneumoniae driven by multiple mechanisms of resistance transmission at a large academic burn center. Antimicrob Agents Chemother, 2017; 61(2). doi 10.1128/AAC.01516-16.

20.

Franceschi

, Gerding

, Phillips

, Fratianne

. Risk factors associated with intravascular catheter infections in burned patients: A prospective, randomized study. J Trauma, 1989; 29:811–8116.

21.

Tomkins

, Burke

. Infections in burn wound. In: Bennett

, Brachman

, eds. Hospital Infections, 3rd ed. Boston: Little, Brown, 1992.

22.

Richet

, Hubert

, Nitemberg

, et al. Prospective multicenter study of vascular-catheter-related complications and risk factors for positive central-catheter cultures in intensive care unit patients. J Clin Microbiol, 1990; 28:2520–2525.

23.

Chen

, Chen

, Sun

. Incidence and mortality of healthcare-associated infections in hospitalized patients with moderate to severe burns. J Crit Care, 2019; 54:185–190.

24.

Bell

, O'Grady

. Prevention of central line-associated bloodstream infections. Infect Dis Clin North Am, 2017; 31:551–559.

25.

Platt

, Polk

, Murdock

, Rosner

. Risk factors for nosocomial urinary tract infection. Am J Epidemiol, 1986; 124:977–985.

26.

, Nicolle

, Coffin

, et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol, 2014; 35(Suppl 2):S32–S47.

27.

Patel

, Paratz

, Mallet

, et al. Characteristics of bloodstream infections in burn patients: An 11-year retrospective study. Burns, 2012; 38:685–690.

28.

Fochtmann-Frana

, Freystätter

, Vorstandlechner

, et al. Incidence of risk factors for bloodstream infections in patients with major burns receiving intensive care: A retrospective single-center cohort study. Burns, 2018; 44:784–792.

29.

Murray

, Loo

, Hospenthal

, et al. Incidence of systemic fungal infection and related mortality following severe burns. Burns, 2008; 34:1108–1112.

30.

Lee

, Jang

, Choi

, et al. Blood stream infections in patients in the burn intensive care unit. Infect Chemother, 2013; 45:194–201.

31.

Raz-Pasteur

, Hussein

, Finkelstein

, et al. Blood stream infections (BSI) in severe burn patients: Early and late BSI: A 9-year study. Burns, 2013; 39:636–642.

32.

Magill

, O'Leary

, Janelle

, et al. Changes in prevalence of health care-associated infections in U.S. hospitals. N Engl J Med, 2018; 379:1732–1744.

33.

Deitch

. Intestinal permeability is increased in burn patients shortly after injury. Surgery, 1990; 107:411–416.

34.

Earley

, Akhtar

, Green

, et al. Burn injury alters the intestinal microbiome and increases gut permeability and bacterial translocation. PLoS One, 2015; 10:e0129996.

35.

Marshall

, Christou

, Meakins

. The gastrointestinal tract: The “undrained abscess” of multiple organ failure. Ann Surg, 1993; 218:111–119.

36.

Pruitt

. The diagnosis and treatment of infection in the burn patient. Burns Incl Therm Inj, 1984; 11:79–91.

37.

Pruitt

, McManus

, Kim

, Goodwin

. Burn wound infections: Current status. World J Surg, 1998; 22:135–145.

38.

Greenhalgh

, Saffle

, Holmes

, et al. American Burn Association Consensus Conference to Define Sepsis and Infection in Burns. J Burn Care Res, 2007; 28:776–790.

39.

Muñoz

, Suárez-Sánchez

, Hernández-Hernández

, et al. From traditional biochemical signals to molecular markers for detection of sepsis after burn injuries. Burns, 2019; 45:16–31.

40.

Cabral

, Afreixo

, Almeida

, Paiva

. The use of procalcitonin (PCT) for diagnosis of sepsis in burn patients: A meta-analysis. PLoS One, 2016; 11:e0168475.

41.

Ren

, Li

, Han

, Hu

. Serum procalcitonin as a diagnostic biomarker for sepsis in burned patients: A meta-analysis. Burns, 2015; 41:502–509.

42.

Oueslati

, Bousselmi

, Rahmani

, et al. Biomarkers of sepsis in burn patients. Crit Care, 2010;14:46.

43.

Halstead

, Rauf

, Bamford

, et al. Antimicrobial dressings: Comparison of the ability of a panel of dressings to prevent biofilm formation by key burn wound pathogens. Burns, 2015; 41:1683–1694.

44.

Halstead

, Rauf

, Moiemen

, et al. The antibacterial activity of acetic acid against biofilm-producing pathogens of relevance to burns patients. PLoS One, 2015; 10:e0136190.

45.

Halstead

, Lee

, Kwei

, et al. A systematic review of quantitative burn wound microbiology in the management of burns patients. Burns, 2018; 44:39–56.

46.

DaCosta

, Kulbatski

, Lindvere-Teene

, et al. Point-of-care autofluorescence imaging for real-time sampling and treatment guidance of bioburden in chronic wounds: First-in-human results. PLoS One, 2015; 10:e0116623.

47.

Mann-Salinas

, Baun

, Meininger

, et al. Novel predictors of sepsis outperform the American Burn Association sepsis criteria in the burn intensive care unit patient. J Burn Care Res, 2013; 34:31–43.

48.

Singer

, Deutschman

, Seymour

, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 2016; 315:801–810.

49.

Yan

, Hill

, Rehou

, et al. Sepsis criteria versus clinical diagnosis of sepsis in burn patients: A validation of current sepsis scores. Surgery, 2018; 164:1241–1245.

50.

Stanojcic

, Vinaik

, Jeschke

. Status and challenges of predicting and diagnosing sepsis in burn patients. Surg Infect, 2018; 19:168–175.

51.

Saaiq

, Zaib

, Ahmad

. Early excision and grafting versus delayed excision and grafting of deep thermal burns up to 40% total body surface area: A comparison of outcome. Ann Burns Fire Disasters, 2012; 25:143–147.

52.

Singer

, Toussaint

, Chung

, et al. Early versus delayed excision and grafting of full-thickness burns in a porcine model: A randomized study. Plast Reconstr Surg, 2016; 137:972e–979e.

53.

Omar

, Hassan

. Evaluation of hand function after early excision and skin grafting of burns versus delayed skin grafting: A randomized clinical trial. Burns, 2011; 37:707–713.

54.

Rhodes

, Evans

, Alhazzani

, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med, 2017; 43:304–377.

55.

Howell

, Davis

. Management of sepsis and septic shock. JAMA, 2017; 317:847–848.

56.

Finfer

, Bellomo

, Boyce

, et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med, 2004; 350:2247–2256.

57.

Eljaiek

, Heylbroeck

, Dubois

. Albumin administration for fluid resuscitation in burn patients: A systematic review and meta-analysis. Burns, 2017; 43:17–24.

58.

Brusselaers

, Hoste

, Monstrey

, et al. Outcome and changes over time in survival following severe burns from 1985 to 2004. Intensive Care Med, 2005; 31:1648–1653.

59.

McGwin

, Cross

, Ford

, Rue

. Long-term trends in mortality according to age among adult burn patients. J Burn Care Rehabil, 2003; 24:21–25.

60.

International Society for Burn Injuries Practice Guideline

Committee

, Steering

Subcommittee

, Advisory

Subcommittee

. ISBI Practice Guidelines for Burn Care. Burns, 2016; 42:953–1021.

61.

Siegel

, Rhinehart

, Jackson

, et al. Management of multidrug-resistant organisms in health care settings, 2006. Am J Infect Control, 2007; 35(10 Suppl 2):S165–S193.

62.

Barlam

, Cosgrove

, Abbo

, et al. Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis, 2016; 62:e51–e77.