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218
J. E. Marcus et al.
There are research studies suggesting use of circulating fungal DNA to facilitate earlier diagnosis of fungal infec­tions, but this is not yet available for clinical use [28].
Microbiology
After burn injuries, the initial sterilization of the burn site and eschar is rapidly followed by gram-positive colonization with a slow evolution to gram-negative bacteria and yeast, especially if there is antimicrobial pressure [29, 30]. Anaerobic bacteria are not thought to play a large role in burn wound infections [31]. This transition from early gram- positive colo­nization to gram-negatives and fungi has been shown repeat­edly in single center studies. For example, one retrospective Dutch study looking at surveillance cultures on admission to a burn unit rarely showed drug-resistant or invasive species [32]. Within 24h of admission, surveillance cultures showed pathologic species in up to a third of patients [33]. This was echoed in a different center where surveillance cultures had growth of gram-positive organisms on median day 4 versus median day 9 for gram-negative organisms [3].
Historically, one of the most concerning early gram­positive organisms was beta-hemolytic Streptococcus species, which can cause necrotizing infections [34]. Many burn cen­ters would treat with five days of penicillin after admission to prevent this dreaded complication. However, with the mod­ern strategy of early debridement, these infections became less common and penicillin prophylaxis appropriately has fallen out of favor [35]. Methicillin-resistant Staphylococcus aureus has become a more common pathogen in modern burn studies and many centers screen patients on admission and then weekly to facilitate early decolonization with appro­priate topical agents [36].
Gram-negative organisms have also become more common causes of burn wound infections with Enterobacteriaceae such as Escherichia coli and Klebsiella pneumoniae are also commonly found throughout a patient’s hospitalization, but
Chapter 9. Burn Wound Infection
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generally are seen in the first several weeks of hospitalization [1, 3, 37]. Pseudomonas aeruginosa and other multidrug-resis­tant organisms appear after several weeks of hospitalization, causing 55% of bacterial infections after day 28 of hospitaliza­tion [1]. With improved early resuscitation of burn patients, associated hospitalizations have lengthened, which may be a contributor to the increased isolation of multidrug-resistant gram-negative organisms [38]. While one study has suggested that antibiotic resistance is uniform across many centers, the general consensus is that organisms are unique to each center requiring ongoing surveillance [39]. Furthermore, the Infectious Diseases Society of America recommends the cre­ation of an antibiogram with stratification within institutions to reduce use of unnecessary or ineffective antibiotics [40].
Fungal pathogens are a less frequent cause of burn wound infections, but have significant associated mortality—equiva­lent to having an extra 33% TBSA burn in one study [26, 41]. Infections typically occur after the second week of hospital­ization and are usually preceded by a period of colonization before development of infection [26]. Candida species tend to originate from the patient’s own gastrointestinal tract and appear after broad-spectrum antibiotic use. Rates of Candida isolation appear lower with early use of autograft skin in burn injuries as compared to other means of skin coverage [42]. While Candida species are the most common fungal organ­ism isolated, most are non- pathogenic, whereas molds are more pathogenic [26, 43]. Infections with molds are associ­ated with a higher mortality than yeasts, with Aspergillus species being the most common, followed by members of Mucorales, including Rhizopus and Mucor [41]. Infections with Mucorales species are associated with significant mortal­ity, even in the setting of rapid debridement and appropriate antifungal therapy [44].
While viral infections, specifically herpesviruses, may re-activate or cause primary infection during burn injuries, they normally are not the cause of burn wound infections. Varicella, in particular, is an important virus in children with burns, but is beyond the scope of this chapter [45].
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Treatment
Topical
Topical antimicrobials represent an important component both for the prevention and treatment of burn wound infec­tions (Table9.2). While surgical debridement of infected tis­sue is fundamental, topical antibiotics are an adjuvant therapy that can improve outcomes [46]. Topical antimicrobi­als are administered over the entire burned surface at differ­ent intervals depending on the formulation. Each topical antimicrobial has its own spectrum of coverage and toxicity profile [37].
The distinguishing features of the most common topical antiseptics used for burn injuries are shown in the table. Some key points to note of individual therapies include:
Silver-based therapies: Silver may be applied topically as either a solution or through an impregnated-dressing. Both methods of delivery have the benefit of efficacy even against multidrug-resistant organisms. The main advantage of these therapies is their long record of use in many different burn centers with no documented evidence of resistance. However, unfortunately, silver solutions cannot penetrate eschar [47,
48]. While these antimicrobials are the most widely used, the
largest systematic review to look at burn injuries found that there has not been definitive proof that using silver-based topical solutions reduced the number of burn wound infec­tions [49]. Side effects of all silver containing therapies include toxicities to fibroblasts and thus should be used with caution [50, 51]. Small studies comparing nanocrystalline sil­ver dressings to silver solutions have not found differences in wound healing [50]. The electrolyte abnormalities of silver nitrate are more prevalent with larger burn TBSA applica­tion, but are seen with as little as 15% TBSA [52, 53]. Silver nitrate may also cause skin discoloration, which makes it more difficult to monitor the wound over time.
Mafenide acetate: Mafenide acetate has the broadest gram­negative coverage of any topical antimicrobials used in burn
Gram
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Unclear of duration of efficacy and stability of
negative Fungal Notes
preparations
Chapter 9. Burn Wound Infection
application site
Rarely used with concomitant inhalational injury
due to acidosis
discoloration (common), fibroblast toxicity
Metabolic side effects frequency proportional to
221
TBSA applied
toxicity
Gram
positive
Eschar
penetration
Unknown ++ ++ ++ Side effects: Cytotoxicity to fibrocytes
2–4 times a
day or
T . Common topical antiseptics used in patients with burn injuries
Topical antiseptic Application
Sodium hypochlorite
solution (Dakin’s
Good + +++ Side effects: Acidosis (common), pain at
continuous
drip
2–4 times
a day
solution), 0.025–0.25%
solution
Mafenide acetate,
5% solution
Unknown +++ + Side effects: Painful application
Good +++ Minimal toxicity
1–3 times
a day
a day
Weekly Moderate ++ ++ + Side effects: Fibroblast toxicity
Mupirocin, 2%
ointment
Nystatin, 6M units/gram 2–3 times
Nanocrystalline
silver dressings
Poor ++ ++ + Side effects: Hyponatremia, hypochloremia, skin
2–4 times
a day or
continuous
drip
Silver nitrate,
0.5% solution
Daily Poor ++ ++ + Side effects: Leukopenia (common), fibroblast
Silver sulfadiazine, 1%
cream
Adapted from Blyth etal, Cartotto etal., Stefanides etal.
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J. E. Marcus et al.
care and has full penetration of the eschar [48, 54]. However, the associated risk of metabolic acidosis limits its use early in resuscitation and in those with concomitant inhalational injury. When used, monitoring for development of acidosis is recommended [55].
Mupirocin: This agent has been associated with the most gram-positive coverage in patients with burns when topically applied to the wound [54, 56, 57]. However, the use of nasal mupirocin has minimal effect in preventing Staphylococcus
aureus burn wound colonization [58].
Other topical agents: Dakin’s solution is notable for its
broad spectrum of activity against bacteria as well as fungi, but its fibroblast toxicity limits its use [59]. The duration of efficacy is unclear and is a major challenge to the use of Dakin’s solution. Nystatin is a potent antifungal that must be used in combination with an antibacterial topical treatment, as it has no antibacterial activity [60]
Systemic
Systemic antibiotics are often used in the treatment of burn wound infections but have no role as prophylaxis to prevent infections in patients with burns. The largest study using sys­temic antimicrobials in patients with burn injuries was per­formed in pediatric patients and resulted in no reduction in the development of wound infections and was associated with longer hospitalizations [61]. When infections develop, treatment should be guided by wound culture. Dosing of sys­temic antimicrobials in patients with burn injuries is complex due to a variety of factors including the significant fluids or blood products a patient receives, the hypermetabolic state associated with burns, and the common use of renal replace­ment therapy. Due to these factors, consideration should be made for a higher dose of systemic antibiotics than for patients without burn injuries [62, 63].
Chapter 9. Burn Wound Infection
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In general, systemic antibiotics should be targeted based on either burn center or patient specific resistance patterns and balance the benefits of therapy with the possible side effects. As described previously, systemic antibiotics are rarely the sole treatment for burn wound infections and should be used in conjunction with topical therapies and debridement. Close collaboration between experts in burn, critical care, infectious diseases, and pharmacology is needed to determine optimal dosing and duration, which is generally a short course once source control is achieved.
Invasive fungal infections are serious infections with a high associated mortality. The bedrock of therapy is surgical excision as an early study showed no surviving patients in groups treated with antifungals alone [64]. In conjunction with debridement, broad-spectrum antifungals are commonly used for empiric treatment of invasive fungal infections in addition to topical therapies. While voriconazole is com­monly used for Aspergillus infections, mucormycosis has inherent resistance to this agent. As there is significant time required to identify the fungal pathogens, a combination of voriconazole and amphotericin is often used empirically while cultures are pending. Histology is generally not suffi­cient to make the correct identification of mold and clinicians should wait for cultures to return before narrowing antifun­gals. In a different population with significant risk of invasive fungal infections, the military’s Clinical Practice Guidelines may provide a reference for therapy for invasive fungal infec­tions, as they are commonly encountered in both populations [65]. Mold-active agents such as isavuconazole and posacon­azole are being used more frequently in burn centers. With favorable safety profile, their use in the burn population compared to voriconazole and amphotericin is an area that warrants further investigation. Fungal infections generally receive at least two weeks of therapy after source control is achieved although it can be longer particularly if multiple body regions are affected [65].
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Prevention
The incidence of burn wound infections has decreased significantly over the past several decades with early excision and skin grafting and the use of topical antimicrobials. However, despite these interventions, there are still outbreaks of burn wound infections [66].
Changes in the design of burn units have been shown to reduce the number of nosocomial infections. Patients should be consolidated to a single ward separated from other patients, with limits to the entry of people to the unit. All procedures, including surgical procedures would ideally occur in this unit to prevent transmission of bacteria from other parts of the hospital [1]. In general, patients with burns should be in individual rooms as they result in significantly less infections than when in open bays [67].
One area of the burn unit that has been tied to wound infection outbreaks in the past has been the Hubbard tanks for immersion hydrotherapy [68]. Even when the same water was not shared between patients, outbreaks occurred due to contamination of different components of the system [69]. Due to this risk, there has been a rapid transition to shower hydrotherapy. In 2010, only 10% of centers routinely per­formed immersion hydrotherapy [70]. Some centers have introduced chlorhexidine baths to reduce hospital acquired infections in patients with burns, where retrospective studies have shown to decrease wound colonization without delaying wound healing [71].
Providers, including physicians, nurses, therapists, and patient care technicians, should be rigorous about hand hygiene. It is standard practice in burn centers for all pro­viders to wear new disposable gowns and gloves with each entry into a patient’s room and to use individualized equip­ment for each patient rather than sharing equipment amongst different patients on a ward. In the burn intensive care unit, nurses should be assigned to patients on a 1:1 ratio to prevent transmission of infectious agents from one room to another [72].
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Conclusion
Burn wound infections are decreasing in the setting of early debridement, topical antimicrobials, improved patient isola­tion, and decreased sharing of communal equipment in the care of burn patients. Diagnosis should be driven by changes in the wound appearance or patient hemodynamics. Gram­positive organisms predominate early in the patient’s hospi­talization with gram-negative bacterial and fungal infections appearing later in a patient’s hospital course. Fungal infec­tions are particularly concerning and have great morbidity associated with them. While there is variability in the treat­ment of patients with burn wounds, surgical debridement is the bedrock of therapy with addition of topical and systemic antimicrobials. Empiric antimicrobials should be guided by the unit antibiogram and/or patient’s surveillance culture data, with subsequent narrowing based on cultures obtained at diagnosis. While more research is needed by multicenter trials to determine the optimal medication selection and treatment for burn wound infections, rigorous infection con­trol practices must be upheld to continue to reduce the impact of these infections on patients with burn injuries.
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