Hindawi Publishing Corporation

ISRN Infectious Diseases

Volume 2014, Article ID 208072, 8 pages
http://dx.doi.org/10.1155/2014/208072

Review Article
Necrotizing Fasciitis: Diagnostic Challenges and
Current Practices

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Abhishek Vijayakumar, Rajeev Pullagura, and Durganna Thimmappa

Karnataka 560002, India

Correspondence should be addressed to Abhishek Vijayakumar; abhishekbmc@yahoo.co.in

Received 12 November 2013; Accepted 5 December 2013; Published 22 January 2014

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Department of General Surgery, Victoria Hospital, Bangalore Medical College and Research Institute, Bangalore,

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Academic Editors: E. Çiftçi and R. Favory

Copyright © 2014 Abhishek Vijayakumar et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.

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Necrotizing fasciitis or necrotizing soft-tissue infections (NSTIs) are infrequent but highly lethal infections. They can be defined
as infections of any of the layers within the soft tissue compartment (dermis, subcutaneous tissue, superficial fascia, deep fascia, or
muscle) that are associated with necrotizing changes. At onset, necrotizing fasciitis can be difficult to differentiate from cellulitis
and other superficial infections of the skin. In fact, only 15% to 34% of patients with necrotizing fasciitis have an accurate admitting
diagnosis. Early diagnosis and management with surgical debridement, antimicrobials, and supportive measures reduce mortality.

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Even with modern ICU care mortality ranges between 16 and 36%; this is related to delays in diagnosis and comorbidities. Various
scoring systems have been developed which help in diagnosis and stratifying patients into risk groups. The present review deals
with varied presentation, early diagnosis, and management of necrotizing fasciitis.

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1. Introduction patients with NF have an accurate admitting diagnosis [5, 6].
Only early diagnosis and aggressive surgical treatment can
Necrotizing fasciitis (NF) or necrotizing soft-tissue infections
reduce mortality and morbidity. Family physicians are often
(NSTIs) are infrequent but highly lethal infections. They

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can be defined as infections of any of the layers within
the soft tissue compartment (dermis, subcutaneous tissue,
superficial fascia, deep fascia, or muscle) that are associated
with necrotizing changes. NSTIs are typically not associated
with abscesses, although they can originate from an untreated
or inadequately drained abscess. These infections were first
described by Jones [1] in 1871 and at the time were termed
“hospital gangrene” that had a mortality of 46%. Shortly after-
wards, Jean-Alfred Fournier [2] described a type of soft tissue
infection affecting the male perineal region, now known as
Fournier’s gangrene. This definition has been expanded
recently to include necrotizing infections of the perineum of
men and women. Surgical debridement was first performed
by Meleney [3] in the early 1920s and has remained an integral
part of current treatment. In 1951, Wilson [4] coined the term
“necrotizing fasciitis” to encompass some of these infections.
At onset, necrotizing fasciitis can be difficult to differ-
entiate from cellulitis and other superficial infections of the
skin. In fact, studies have shown that only 15% to 34% of
the first point of contact for these patients, and a high index of
suspicion is needed, as there is a paucity of initial signs. The
current review deals with presentation, early diagnosis, and
management of necrotizing fasciitis.
2. Classification
There is a great deal of confusion surrounding the identifica-
tion and definition of necrotizing fasciitis. Historically, necro-
tizing infections were classified according to anatomical sites.
Fournier’s gangrene (involving the perineum) and Ludwig
angina (involving submandibular and sublingual spaces) and
Meleney synergistic gangrene (involving abdominal wall) are
examples. These infections were named after the physicians
who first described them.
In 1972 Baxter [7] divided soft tissue infections into three
categories based on surgical management (Table 1).
Lewis [8] proposed an alternate classification system that
grouped NSTIs into three anatomic categories (Table 2).
2 ISRN Infectious Diseases

Table 1: Classification of soft tissue infections based on treatment Table 3: Classification of necrotizing fasciitis based on microbiol-
modality according to Baxter. ogy.

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Surgical lesions requiring radical incision and drainage Type 1
Acute streptococcal hemolytic gangrene Polymicrobial infections including anaerobes
Necrotizing fasciitis Type 2
Streptococcal myositis Streptococcus pyogenes (Group A Streptococcus)

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Clostridial cellulitis Staphylococcus aureus, including methicillin-sensitive and
Gram-negative anaerobic cutaneous gangrene resistant
Surgical infections requiring excision of tissue Other microbiological etiologies
Progressive bacterial synergistic gangrene Vibrio vulnificus

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Nonclostridial gas-producing infections Aeromonas hydrophila
Nonclostridial myositis Enterobacteriaceae (Escherichia coli, Pseudomonas spp., and
Klebsiella spp.)
Human bite infections
Nonoperative infections

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Erysipelas Table 4: Risk factors for necrotizing fasciitis.
Lymphangitis and lymphadenitis
Age greater than 50 years
Purpura fulminans
Atherosclerosis
Burns

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Table 2: Classification of soft tissue infections by Lewis. Cancer or other
Immunocompromised state
Infections of skin and subcutaneous tissue
Chronic alcoholism
Progressive synergistic bacterial gangrene
Chronic undermining burrowing ulcer (Meleney’s ulcer) Corticosteroid use

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Idiopathic scrotal gangrene (Fournier’s gangrene) Diabetes mellitus
Infections involving subcutaneous tissue and fascia Hypoalbuminemia
Hemolytic streptococcal gangrene Intravenous drug abuse
Necrotizing fasciitis Malnutrition

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Gram-negative synergistic necrotizing cellulitis Obesity
Clostridial cellulitis Occult diverticulitis
Infections involving muscle
Peripheral vascular disease
Clostridial myonecrosis
Postoperative infection

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Streptococcal myositis
Trauma

Another classification of necrotizing fasciitis into type 1

and type 2 based on microbial cause is used (Table 3). 4. Etiology

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3. Risk Factors
The precise origin of necrotizing fasciitis is often unclear.
Introduction of the pathogenic agent or agents can occur as
a result of minor trauma, insect bite, or surgical incision.
Hematogenous spread from distal sites of infection has also
been reported [9]. Other potential sources include odon-
togenic infections [10], varicella lesions [11], intramuscular
injections [12], and contusions [13]. Some cases of NF occur
in the absence of any apparent prior trauma [14]. Various risk
factors have been identified in development of NF (Table 4).
Nonsteroidal anti-inflammatory drug use has been impli-
cated in severe necrotizing streptococcal infections. It is
postulated that nonsteroidal anti-inflammatory drugs impair
lymphocyte function [15]. However, it could also be that sup-
pression of symptoms and signs of inflammation leads to later
diagnosis, especially in patients presenting early with nonspe-
cific symptoms [16].
Although necrotizing soft tissue infections can be monomi-
crobial, they usually are synergistic polymicrobial infections.
In an analysis of wound and blood cultures, blood cultures
with a single organism, multiple organisms, and no organism
were found in 27%, 2%, and 71% of cases, respectively. For
the wound cultures, a single organism, multiple organisms,
and no organism were found in 53%, 23%, and 23% of cases,
respectively [17].
In a study by Elliott et al. [18] it was found that only 28
of 182 patients developed necrotizing skin infections from
single pathogens; the other 154 patients had polymicrobial
infections (average of 4.4 organisms in the original wound
cultures). In this series, the majority of monomicrobial
infections were caused by streptococcal isolates such as
beta-hemolytic streptococci (namely, Group A streptococci
or Streptococcus pyogenes). Other common monomicro-
bial necrotizing soft tissue infections include Staphylococcus
aureus and Clostridium perfringens.
ISRN Infectious Diseases
Table 5: Clinical features of necrotizing fasciitis.
Skin Pain
Erythema with ill-defined margins Pain that extends past margin of apparent infection
Tense edema with grayish or brown
Severe pain that appears disproportionate to physical findings
discharge
Lack of lymphangitis or lymphadenopathy Decreased pain or anesthesia at apparent site of infection
Vesicles or bullae, hemorrhagic bullae
Necrosis
Crepitus
The organisms most common in polymicrobial necrotiz-
ing soft tissue infections are combinations of staphylococci
(especially Staphylococcus epidermidis with beta-hemolytic
streptococci), enterococci, Enterobacteriaceae species (com-
monly Escherichia coli, Proteus mirabilis, Klebsiella pneu-
moniae, and Pseudomonas aeruginosa), streptococci, Bac-
teroides/Prevotella species, anaerobic gram-positive cocci,
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and Clostridium species [19].
5. Clinical Presentation
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Necrotizing infections can occur anywhere in the body,
although some anatomic locations are affected more com-
monly. Most necrotizing soft tissue infections occur in the
extremities, abdomen, groin, and perineum. In a case series,
these infections were discovered in the extremities (53 per-
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cent of cases), perineum or buttocks (20 percent), trunk (18
percent), and head and neck (8.9 percent) [20].
As NF first starts in the deep tissue planes, at initial
presentation there might be minimal epidermal involvement.
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This can make it difficult to differentiate from nonnecrotizing
skin infections and cellulitis. Also minor trauma which
presents as cellulitis may have deeper plane extension and
may initially be missed. Patients with NF are usually system-
ically toxic, presenting with fever (temperature greater than
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38∘ C), tachycardia, diaphoresis, and even an altered mental
state or diabetic ketoacidosis. The physical examination
should include all parts of the body to search for skin inflam-
mation. This is important in patients presenting with sepsis
with no obvious skin lesions. The perineum and oral cavity
are areas that can be easily missed [21]. Also a search for other
source of infection which can underlay necrotizing fascitis
needs to be made like appendicitis, perforated diverticulitis,
and cholecystitis intraabdominal abscess.
Erysipelas, being an infection of the superficial dermis,
has well-defined borders and often blister. In cellulitis, there is
predominance of erythema lymphangitis with minimal blis-
tering. Necrotizing fasciitis typically presents with patchy dis-
colouration of the skin with pain and swelling, but without a
defined margin or lymphangitis [22]. Progression of NF is
marked with the development of tense edema, a grayish-
brown discharge, vesicles, bullae, necrosis, and crepitus [23]
(Table 5). Hemorrhagic bullae and crepitus are serious signs,
with the likelihood of underlying fascia and muscle being
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General
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Fever with toxic appearance
Altered mental state
Tachycardia
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Tachypnea due to acidosis
Dehydration
Decreased urine output
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Presentation with diabetic
keto acidosis
compromised [24]. Crepitus is a late sign and is found in only
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about 18% of cases of NF [25]. Although crepitus and blister-
ing are the most specific signs of necrotizing soft tissue infec-
tion, they are not sensitive. Two retrospective case series, by
Wang et al. [26] and Elliott et al. [27], reported an absence of
crepitus in 62% to 73% of cases and an absence of blistering in
76% to 95% of cases upon initial presentation. There is usually
absence of collection of pus which delays surgical consult or
delays intervention by surgeon.
Severe localized pain is another feature of NF. As the
disease is a deep-seated infection, the epidermis is minimally
involved at initial presentation. The patient might complain of
pain out of proportion to the degree of dermal involvement
or pain that extends past the apparent margin of infection.
Patients with diabetic neuropathy may have minimal pain
resulting in a missed diagnosis. This is especially likely in con-
cealed sites of infection, such as the perineum or oral cavity. A
patch of anesthesia over the site of erythema is also sometimes
described in NF. This is thought to be due to infarction of
cutaneous nerves in necrotic subcutaneous fascia and soft
tissue [28].
There are some specific types of necrotizing fasciitis with
characteristic features.
5.1. Necrotizing Cellulitis. Necrotizing cellulitis, or hemolytic
streptococcal gangrene, generally presents shortly after minor
trauma. Patients have findings consistent with cellulitis,
including erythema, warmth, and swelling. Unlike other
cellulitis severe pain is common. There may be rapid develop-
ment of gas distal to the wound and blebs which contain dark
serous fluid.
5.2. Streptococcal Myositis. The hallmarks of streptococcal
myositis are severe local pain and toxemia. Wounds have a
foul odor, discoloration, and edema. Patients might develop
blebs and gangrene of the overlying skin, although disease
progression is characteristically slow. Underlying muscle is
not viable and will require excision.
5.3. Clostridial Cellulitis. One of the most important histori-
cal findings associated with clostridial cellulitis is severe pain
occurring days after local tissue injury. Patients subsequently
4 ISRN Infectious Diseases

develop skin blebs that contain a reddish-brown, foul- Table 6: Laboratory risk indicator for necrotizing fasciitis
smelling fluid. There is rapid progression of cellulitis over (LRINEC) score to help discriminate between necrotizing and
hours and patient is toxic. Crepitus might be noted, but it is nonnecrotizing soft-tissue infections.

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not a universal finding.
Value Score
C-reactive protein, mg/dL
5.4. Progressive Bacterial Synergistic Gangrene or Meleney’s <150 0
Gangrene. According to Baxter, progressive bacterial syner-

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>150 4
gistic gangrene (PBSG) and Meleney’s ulcer represent vari-
WBC count, cells/mm3
ants of the same disease process, but Lewis describes them as
two separate entities. Despite differences, similar clinical pro- <15 k 0
files are noted. PBSG is a rapidly progressive infection caused 15–25 k 1

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by nonhemolytic streptococci in association with hemolytic >25 k 2
staphylococci or gram-negative bacilli. It is most commonly Hemoglobin level, g/dL
found following abdominal surgeries with infected wound. >13.5 0
Clinical presentation is notable for a wound with a central 11–13.5 1
necrotic area that is surrounded by purple, erythematous <11 2

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zones of skin. In addition, necrotic tracts can extend through Sodium level, mmol/L
the underlying tissue, resulting in additional ulcerations at >135 0
sites distant from the primary lesion. <135 2
Creatinine level, mg/dL
5.5. Fournier’s Gangrene. Fournier’s gangrene is an acute, <1.6 0

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rapidly progressive, and potentially fatal, infective necrotiz- >11.6 2
ing fasciitis affecting the external genitalia, perineal, or peri-
Glucose level, mg/dL
anal regions, which commonly affects men but can also occur
<180 0
in women and children. The clinical features of Fournier’s
gangrene include sudden pain in the scrotum, prostration, >180 1

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pallor, and pyrexia. At first only the scrotum is involved, but if Risk category: low <5 (<50% chance of NF), intermediate 6-7 (50–75%
chance of NF), and high 8 (>75% chance of NF).
unchecked, the cellulitis spreads until the entire scrotal cover-
ings slough, leaving the testes exposed but healthy. One over-
whelming feature of the presentation is the strong “repulsive,
was associated with NSTI and that a combination of both

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fetid odour” that is associated with the condition. Patients
increased the likelihood of NSTI. It had a negative predictive
can present with varying signs and symptoms including fever
value (NPV) of 99%, but not very specific, with a positive
greater than 38∘ C, scrotal swelling and erythema, purulence
predictive value (PPV) of only 26%.
or wound discharge, crepitation, or fluctulance [29].
Wong et al. [31] devised a scoring system (laboratory

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6. Diagnostic Tools
There are a wide variety of diagnostic tools that have been
described and tested to diagnose NF more accurately and
risk indicator for necrotizing fasciitis score) to discrimi-
nate between NSTI and nonnecrotizing soft-tissue infec-
tion (Table 6). They compared a set of laboratory variables
between patients with and without NSTI and identified 6
independent variables associated with NSTI. The total score

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expeditiously. Even in the most experienced hands, clinical
findings are not accurate enough for diagnosis, and both clin-
ical clues and diagnostic tools should be used in combination
to help make an early diagnosis.
6.1. Laboratory Testing. Abnormal laboratory findings
include an elevated white blood cell (WBC) count, azotemia,
abnormal coagulation profiles, and decreased platelet and
fibrinogen levels. Other laboratory findings such as elevated
lactate and blood glucose levels, hypocalcemia, hypoalbu-
minemia, and anemia are also commonly found. The sensi-
tivity of these studies varies, although leukocytosis and hyp-
onatremia have been found to be predictive of necrotizing
infection.
Wall et al. [30], in a retrospective study, compared a set of
admission variables of patients with NSTI and patients with
nonnecrotizing soft-tissue infection. After univariate and
multivariate analysis, they found that having a WBC count
>15,400 cells/mm3 or a serum sodium level <135 mmol/L
had a range of 0–13, and patients were categorized according
to the risk of NSTI among 3 groups. Wong and colleagues
showed that, for intermediate and high-risk patients (score
>6), the score had a PPV of 92% and a NPV of 96%. This
constitutes a great tool for both confirming and discarding
NSTI and has the advantage that it is based on laboratory
variables that are widely available across different institutions.
Plain X-ray films can demonstrate subcutaneous gas, but
this is a specific, not a sensitive, finding (positive in fewer than
25% of cases) and absence of gas does not exclude NF [32].
Computed tomography and magnetic resonance imaging
(MRI) might be useful in cases where signs are equivocal or
diagnosis is in doubt. Asymmetrical fascial thickening, fat
stranding, and gas tracking along fascial planes are important
imaging findings. Computed tomography scans are estimated
to have a sensitivity of 80% for detecting necrotizing soft tis-
sue infections [33]. In cases of cellulitis, MRI will demonstrate
subcutaneous thickening with fluid collection. However,
when there is deep fascia involvement with fluid collection,
ISRN Infectious Diseases
thickening, and enhancement after contrast administration,
necrotizing infections must be considered. According to
Schmid et al. [34] the sensitivity of MRI is 100% with a
specificity of 86%. It is particularly helpful in the investigation
of areas that have disproportionately severe tenderness and
when nonspecific signs of sepsis are present. This has been
disputed, and other authors have argued that in early cases of
NF, MRI might not show fascial involvement [35]. If clinical
suspicion is high, surgeons can opt to explore and perform tis-
sue biopsies rather than delay treatment for imaging studies.
6.2. Biopsy. In clinically suspicious cases where there is no
obvious finding tissue diagnosis may be sought. Fine needle
aspiration (FNA) has been used in the past but is no longer
recommended. Incisional biopsy has largely replaced FNA as
a more sensitive technique. It can be performed at the bedside
under local anesthetic and is advocated in early or equivocal
cases. Standard practice is to take biopsies from a representa-
tive area of the infectious process and from the leading edge
of any erythematous, edematous, necrotic, or indurated area
[36].
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Frozen-section evaluation of an incisional biopsy speci-
men characteristically reveals necrosis, polymorphonuclear
infiltration, microorganisms, vasculitis, and vascular throm-
bosis located in the superficial fascia, deep dermis, and
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surrounding adipose tissue. Sparing of epidermis, superficial
dermis, and underlying muscle tissue is usually noted. Gram
stain of the tissue sample is also a valuable adjunct to clinical
examination and can be performed [37, 38].
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7. Treatment
7.1. Hospitalization. Primary care physicians have to use clin-
ical judgment to decide which patients who present with evi-
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dence of skin inflammation should be hospitalized or receive
further evaluation. It is interesting that only 15% to 34% of
patients with a discharge diagnosis of necrotizing skin and
subcutaneous infection had an admitting diagnosis of NF.
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Studies of patients with soft tissue infection showed that
a history of diabetes mellitus, pyrexia, hand infections, and
an area of inflammation greater than 70 cm2 are independent
predictors of hospitalization [39]. Hospitalization is indicated
for patients with soft tissue infections accompanied by signs
and symptoms of systemic toxicity (fever, hypothermia,
tachycardia (heart rate more than 100 beats/min)), hypoten-
sion (systolic blood pressure less than 90 mm Hg or more
than 20 mm Hg below baseline), an altered mental state,
severe infection (including those requiring formal operative
intervention), intractable nausea and vomiting, immuno-
compromise, failure of outpatient therapy, and poor social
support. The latest Infectious Diseases Society of America
skin and soft tissue infection guidelines indicate that hospi-
talization should be considered in patients with hypotension
and/or an elevated creatinine level, low serum bicarbonate
level, elevated creatine phosphokinase level (2-3 times the
upper limit of normal), marked left shift, or a C-reactive
protein level more than 13 mg/L [40].
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The treatment for NSTI involves the principles of treat-
ment for any kind of surgical infection: source control, anti-
microbial therapy, support, and monitoring.
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7.2. General Management. Patients who have progressive
necrotizing infections often deteriorate rapidly. As soon as the
diagnosis of NSTI is suspected, aggressive resuscitation and
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empiric broad-spectrum antibiotic coverage should be insti-
tuted. Septic shock with intravascular volume depletion and
shunting in the periphery is an ongoing process at the time
of diagnosis. Significant fluid and protein losses occur even
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before surgical debridement, resulting in inadequate tissue
oxygenation. Early resuscitation with blood products and
vasopressins over crystalloids reduce mortality. Main vaso-
pressins used are noradrenaline and dopamine.
Patients presenting with multiorgan failure are admitted
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to surgical intensive care unit (SICU). Invasive hemodynamic
monitoring is routinely implemented when the patient has
been admitted to the SICU with the goal being to achieve an
oxygen delivery greater than 600 mL/min/m2 . Patients pre-
senting with respiratory failure may require prolonged ven-
tilation and tracheostomy is often required. Renal failure is
another frequent complication that might require continuous
hemodialysis [41].
Aggressive nutritional support is mandatory in all
patients after debridement. Patients should receive twice their
basal caloric requirements orally or parenterally. Nutritional
support is associated with fewer complications and lower
morbidity and mortality rates [42]. Pre- and postoperative
pain control is also an important part of management and
should be individualized for each patient.
7.3. Antimicrobial Therapy. Antimicrobial therapy is an
adjunct to source control for the treatment of NF. Broad-spec-
trum antimicrobial therapy should be started early to include
coverage for gram-positive, gram-negative, and anaerobic
organisms. Special consideration for Group A Streptococ-
cus and Clostridium species should be taken. Acceptable
regimens include monotherapy agents, such as imipenem,
meropenem, ertapenem, piperacillin/tazobactam, and tige-
cycline. Multidrug regimens have also been described,
including triple-drug therapy regimens, such as high-dose
penicillin, high-dose clindamycin, and a fluoroquinolone or
an aminoglycoside for coverage of gram-negative organisms.
Vancomycin, daptomycin, or linezolid should be included
in the regimen until methicillin-resistant staphylococcal
infection has been excluded. The use of protein synthesis
inhibitors, such as clindamycin, may help by inhibiting toxin
production, which can be crucial for controlling the inflam-
matory response in patients with NSTI, particularly in those
with clostridial and streptococcal infections. Antimicrobial
administration should be continued until no further debride-
ments are needed and the patient’s physiology has improved.
Prolonged courses of an arbitrary duration are not necessary
and may predispose the patient to wound colonization with
drug-resistant organisms.
In type 2 NF caused by streptococci resulting in strepto-
coccal toxic shock syndrome, intravenous immunoglobulins
6 ISRN Infectious Diseases
might play a therapeutic role. A multicentre, randomized
controlled trial evaluated the safety and efficacy of intra-
venous immunoglobulins in streptococcal toxic shock syn-
drome. The trial was prematurely stopped because of poor
recruitment, but it showed 3.6-fold higher mortality in the
placebo group compared with the treatment group [43].
These studies are also controversial and difficult to compare,
given the small number of patients and the different method-
ologies used. It seems reasonable to use intravenous immune
globulin in patients with group A streptococcal infection who
have developed streptococcal toxic shock syndrome and in
those with a high mortality risk (advanced age, hypotension,
and bacteremia) [44].
7.4. Surgical Management. Whenever NF has been confirmed
surgical debridement is indicated. Some researchers also
advocate surgery as a means for diagnosis in patients for
whom clinical and laboratory findings are still not conclusive
and for whom the diagnosis of NF is still possible. Debride-
ment of the necrotic tissue should be undertaken as soon as
possible. Other researchers have clearly shown the impact of
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early and complete debridement on final outcome in patients
with NF [45, 46].
When comparing earlier and complete with delayed or
incomplete debridements, mortality always has been signif-
icantly lower with the most aggressive strategy. Important
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goals of debridement include removal of heavily contami-
nated tissue and removal of all devitalized tissues that might
otherwise impair host defenses within the wound. Persistent
necrotic tissue serves as a culture medium and creates an
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anaerobic environment in which the bactericidal activity of
polymorphonuclear cells is impaired. During the operation,
a generous incision is performed and macroscopic findings of
the disease are used to help guide the extent of the debride-
ment. An indication of muscle viability is by its response
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to stimulation using hand-held cautery. When contractility
is absent, the muscle is usually not viable and should be
debrided.
Intraoperative administration of intravenous fluorescein
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can be used to determine viability of adjacent soft tissues
when viewed under a Wood’s or ultraviolet (UV) lamp. Ten
minutes after injection of one ampule of fluorescein, exposure
of the operative field to UV light will expose nonperfused
areas that require further debridement. Occasionally, ampu-
tation of a limb is necessary to achieve this goal and is encour-
aged if that is the case. Healthy, viable, bleeding tissue should
be present at the edges of the excision site, and aggressive
resuscitation should accompany the perioperative period.
Once the initial debridement has been done, management
in an intensive care unit is recommended, and scheduled
debridements at intervals of 6–48 h should be performed
until no further necrosis or infected tissue is seen.
7.5. Hyperbaric Oxygen Therapy. Hyperbaric oxygen (HBO)
is generally considered to be an important adjunct in the
treatment of clostridial myonecrosis or gas gangrene. All
necrotizing infections are associated with reduced tissue
oxygen tension, ischemia, and subsequent decrease in host
cellular immunity. Increased oxygen partial pressure has been
associated with the reversal of basic pathophysiologic mech-
anisms of necrosis. Increased oxygen tension also reverses
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ischemia and thereby improves host defense mechanisms
[47, 48]. HBO also enhances the action of various antibiotic
agents by facilitating their transport across the bacterial cell
wall. Various studies have failed to show statistically signifi-
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cant outcome differences with respect to mortality and length
of hospitalization [49]. As a result, HBO is not a mandatory
component of therapy. It might be appropriate in some
patients, but its use should never delay definitive surgical care.
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An HBO treatment regimen usually consists of wound expo-
sure at 2.5 to 3.0 atmospheres and breathing 100% oxygen for
90 minutes every 8 hours for the first 24 hours and then twice
daily. HBO treatment is continued for a minimum of 5 days
and is discontinued when the patient is stable and has no
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evidence of ongoing necrosis [50].
8. Prognosis
Since the first description by Jones, mortality in patients with
NSTI remains high. He reported a mortality rate of 46%, and
a recent pooled analysis determined it to be ∼34% [51].
More recent data indicate a mortality of 16.4% [52] for
community-acquired necrotizing soft tissue infections and
36.3% for postprocedural necrotizing infections [53]. All of
these patients were managed in hospital with intravenous
antibiotics and surgical interventions; considering medical
progress in the last 135 years, mortality is still substantial.
Mortality is higher in patients with streptococcal toxic shock
syndrome. Diabetic patients, especially those presenting with
diabetic ketoacidosis or hyperosmolar hyperglycemic nonke-
totic acidosis, have higher rates of death and longer lengths of
hospital stay [54]. A delay in surgery of more than 24 hours
was an independent risk factor for mortality.
In a recent study that included 350 patients with NF,
Anaya et al. [55] created a score to categorize patients accord-
ing to the risk of mortality. Variables included in the score
were age >50 years, WBC count >40,000 cells/mm3 , hema-
tocrit >50%, heart rate >110 beats/min, temperature >36
degrees Celsius, and creatinine level >1.5 mg/dL. Tools like
this should help to identify high-risk patients who may bene-
fit from novel therapeutic strategies or for selection of patients
for future trials.
There is also considerable postoperative morbidity, some-
times from extensive debridement resulting in muscle loss.
Patients might have to undergo a period of rehabilitation to
regain function of the affected areas. Scarring and disfigure-
ment can also be substantial.
9. Summary
NSTIs are relatively infrequent but highly lethal infections.
They encompass a wide variety of soft-tissue infections
associated with necrosis that share the same diagnostic and
treatment principles. Establishing the diagnosis of NSTI is
one of the biggest challenges in treating patients with NSTI.
Accuracy increases with familiarity of clinical findings and
ISRN Infectious Diseases
knowledge of laboratory, imaging, and macroscopic and
microscopic findings, all combined with a high index of sus-
picion. Treatment includes definitive surgical debridement in
conjunction with antimicrobials and hemodynamic stabiliza-
tion. Surgical debridement should be performed frequently
(even daily) until the acute tissue destruction has been con-
trolled. Outcomes are also influenced by prompt diagnosis,
the timing and extent of surgical treatment, and management
of postoperative complications. Scores that identify high-risk
patients serve to guide novel therapeutic strategies and to
identify patients for future trials.
Conflict of Interests
The authors declare that there is no conflict of interests
regarding the publication of this paper.
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