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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 24h 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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219
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].

220
J. E. Marcus et al.
Treatment
Topical
Topical antimicrobials represent an important component
both for the prevention and treatment of burn wound infections (Table9.2). 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 etal, Cartotto etal., Stefanides etal.

222
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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J. E. Marcus et al.
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].

Chapter 9. Burn Wound Infection
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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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