Diabetic Soft Tissue

Infections
Christine Castater, MD, MBAa,*, Elliot Bishop, MDb,
Adora Santos, DOb, Mari Freedberg, MDb, Phillip Kim, MD
b
,
Christopher Sciarretta, MDc

KEYWORDS
 Diabetic foot  Infection  Diabetes  Necrotizing soft tissue infection
 Soft tissue infections  Cellulitis

KEY POINTS
 Pathophysiology of diabetes is a risk factor for developing soft tissue infections as well as
for wound healing.
 Surgical site infections are increased in poorly controlled diabetic patients.
 Cellulitis and abscesses are more common in diabetic patients because of bacterial colo-
nization and decreased immune competence.
 Because necrotizing soft tissue infections (NSTIs) can progress rapidly and cause sepsis
and even death, diagnosis and surgical debridement must be aggressive and prompt.
 Expedited diagnosis and management of all soft tissue infections associated with dia-
betes is paramount.

INTRODUCTION

Diabetes affects millions of adults worldwide and up to 10% of Americans, so it is

important to understand the health sequelae associated with the disease. Hyperglyce-
mia impairs the immune system and leads to a susceptibility to infections. These infec-
tions can range from cellulitis or abscesses to necrotizing soft tissue infections (NSTIs).
In addition, increased vascular insufficiency and peripheral neuropathy lead to an
increased risk of foot wounds. Most important to the general surgeon is the association
between hyperglycemia and increased surgical site infections (SSIs). The workup and
management of these infections vary, so it is important to understand them. It is impor-
tant to have a high index of suspicion for soft tissue infections in diabetic patients.

a
Morehouse School of Medicine, Grady Memorial Hospital 1C-144, 80 Jesse Hill Jr Drive
Southeast, Atlanta, GA 30303, USA; b Emory University, Grady Memorial Hospital Glenn
Building 69 Jesse Hill Jr Drive Southeast, Atlanta, GA 30303, USA; c University of Tennessee,
University of Tennessee College of Medicine, 975 3rd Avenue, Chattanooga, TN 37403, USA
* Corresponding author. Morehouse School of Medicine, Grady Memorial Hospital, 80 Jesse Hill
Jr Drive SE, Room 2C144, Atlanta, GA 30303.
E-mail address: ccastater@[Link]
Twitter: @grannysurgeon (C.C.)

Surg Clin N Am 103 (2023) 1191–1216

[Link] [Link]
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1192 Castater et al

PATHOPHYSIOLOGY

Diabetes not only puts patients at risk of developing infection but also leads to delayed
wound healing. In particular, this relates to poorly controlled diabetes with hyperglyce-
mia.1 Susceptibility to infection is caused by many factors, including impaired immune
response, vascular insufficiency, peripheral neuropathy, increased asymptomatic
colonization, and organism-specific factors.
Immunologic impairment occurs by multiple complex mechanisms, including
decreased chemotaxis, opsonization, phagocytosis, and wound maturation.2 Neutro-
phil function is reduced owing to decreased tumor necrosis factor-alpha (TNF-alpha)
and interleukin-1 (IL-1) release from macrophages as well as decreased chemotaxin
release.3,4 Hyperglycemia diverts nicotinamide adenine dinucleotide phosphate
from the opsonization pathway, thereby impairing it and decreasing bacterial and
fungal clearance.5 Increased gene induction leads to increased early apoptosis in
wounds, thereby impairing intracellular bactericidal ability and normal wound matura-
tion.6 Reduction in major histocompatibility complex class 1 expression and reduced
production of IL-10, interferon-gamma, and TNF-alpha significantly impair phagocy-
tosis.7 Hyperglycemic inhibition of oligosaccharide binding reduces the function of
many aspects of cell-mediated immunity.8
Vascular disease is common in diabetic patients and can cause local tissue ischemia.
This enhances the growth of certain bacteria while also impeding leukocyte function. It
also impairs the inflammatory response and decreases antibiotic absorption. Peripheral
neuropathy can cause unnoticed wounds to develop into serious infections. In addition,
diabetic patients are more likely to be colonized with bacteria, such as Staphylococcus
aureus including methicillin-resistant strains as well as with pseudomonal species.9
Fungal colonization including with candida and rhizopus (mucor) is also common in dia-
betic patients.10 Hyperglycemia causes glucose-induced proteins to assist Candida
species in epithelial adherence and phagocytosis resistance.11 Mucor species also
thrive in these high-glucose, acidic environments.12

SURGICAL SITE INFECTIONS

SSIs and poor wound healing directly correlate with poor diabetes control and periop-
erative hyperglycemia.13,14 This is due to many of the same cytologic factors that
increase general infection risk. Growth factor production, angiogenic response,
macrophage function, collagen accumulation, epidermal barrier function, quantity of
granulation tissue, and keratinocyte and fibroblast migration and proliferation are all
impaired.15 After retrospectively controlling for other factors, postoperative hypergly-
cemia has been shown to be the sole risk factor for SSI16 with increased levels of hy-
perglycemia directly correlating with increased SSI risk (Fig. 1). This is supported by
both prospective and retrospective data as well as by data showing that perioperative
glycemic control decreases SSI rates.17–19

DIABETIC FOOT WOUNDS

Epidemiology
According to the International Diabetes Federation, it is estimated that 537 million adults
between the ages of 20 and 79 have been diagnosed with diabetes. The prevalence is
predicted to increase to 643 million by 2030 and 783 million by 2045.20 The global annual
incidence of diabetic foot ulcers is estimated to be between 9.1 million and 26.1 million,
with a lifetime incidence as high as 19% to 34%.21 Among the reasons for hospital admis-
sion of a diabetic patient, foot wounds are the most common,22 with an associated

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 Diabetic Soft Tissue Infections 1193

Fig. 1. Risk factors for SSI.

morbidity and mortality as high as 50% across a 5-year period.23 In addition, diabetic foot
ulcers are the leading cause of nontraumatic amputations in the United States,24 and
postamputation mortality increases to 39% to 80% over a 5-year period.25

Pathophysiology
The underlying pathophysiology that leads to the development of a diabetic foot
wound is complex and multifactorial. Poor glycemic control leads to polyneuropathy
and arterial insufficiency predisposing individuals to unrecognized trauma with poor
perfusion, which then increases the risk for wounds, ulcerations, and infections.26
The polyneuropathy caused by diabetes mellitus is attributed to dysfunction of motor,
sensory, and autonomic nerve fibers.27 Dysfunction in peripheral motor fibers leads to
muscle atrophy of the lumbricals and interosseous muscles, which results in anatomic
changes to the arch of the foot. These changes can lead to “claw” deformities of the
toes, hammertoe contractures of digits, and equine ankle deformity28,29 (Fig. 2).
Neuropathy is further complicated by damage to sensory nerve fibers, specifically,
damage to type A and type C fibers. Dysfunction in type A fibers results in loss of pro-
prioception, pressure sensation, vibratory perception, and gait abnormalities. Damage
to type C fibers decreases the ability to perceive painful stimuli30 (Table 1). Changes in

Fig. 2. Hammer toe deformity. Paul Campbell/iStock/Getty Images.

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1194 Castater et al

Table 1
Comparison of type A and type C nerve fibers

Type of Nerve Fiber Function Myelin Diameter

Type A Proprioception Myelinated Large
Type C Pain Nonmyelinated Small

peripheral autonomic nerve fibers cause changes in thermoregulation and anhidrosis,

resulting in disruptions to the skin barrier and subsequent infection risk.31,32 As previ-
ously discussed, unmanaged hyperglycemia leads to endothelial injury and combined
with hyperlipidemia causes atherosclerosis, vascular compromise, and poor tissue
perfusion.33 Decreased perfusion affects immunologic function, leukocyte activity,
and complement function.34,35 Any infection that develops can lead to complications,
such as hospitalization, amputation, and death.

Clinical Manifestation
On initial presentation of a patient with a suspected diabetic foot wound, it is important to
identify what underlying risk factors or comorbidities exist. Pertinent details include glyce-
mic control and regimen, prior ulcers, infections or surgeries, vascular disease, recent or
past trauma causing foot deformity, systemic symptoms (ie, fevers), and tobacco use.36

Physical examination
Clinical examination should include visual inspection and assessment of the vascular,
neurologic, and musculoskeletal systems.37 Evaluation of the skin should pay partic-
ular attention to the dorsal aspect of the toes, plantar surface at the metatarsal heads,
the heel, and the interdigital skin38 (Fig. 3).

Fig. 3. Diabetic foot wound. PS3000/iStock/Getty Images.

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 Diabetic Soft Tissue Infections 1195

Vascular compromise is highly prevalent among patients with diabetes mellitus and
approximately two-thirds of patients presenting with foot ulcers will have peripheral
arterial disease.39 Providers should evaluate for palpable dorsalis pedis and/or poste-
rior tibialis pedal pulses; if absent, further assessment with doppler, ankle-brachial in-
dex, or toe brachial pressure index is recommended.40,41 The clinical examination is
catered more toward identifying the presence of loss of protective sensation rather
than neuropathy, although neuropathy can also be examined.42 Evaluating neuropathy
is done via 10-g monofilament, vibration, touch, and thermal sensation tests21,42–48
(Fig. 4). The musculoskeletal examination should include assessment for gross defor-
mities of both the arch and the toes.49
Not all diabetic foot wounds or ulcers are infected, but roughly 50% to 60% will lead
to infection,50 and 20% of moderate to severe infections will result in amputation.51
Diagnosis typically involves clinical assessment, laboratory studies, and imaging. Dia-
betic foot infections (DFIs) present on a spectrum and can range from superficial skin
infection to osteomyelitis.52 Classic signs of inflammation include erythema, edema,
tenderness, warmth, and purulence (Fig. 5).53

Laboratory workup
Blood tests, such as complete blood count, C-reactive protein, and erythrocyte sedi-
mentation rate (ESR), lack sensitivity and specificity. Up to 50% of patients presenting
with a deep wound infection do not have leukocytosis.54,55

Fig. 4. Bedside examination tools to evaluate large (type A) and small (type B) nerve fiber
function. Large fibers are examined using 10-g monofilament, vibration with 128-Hz tuning
fork, touch and joint position, and small fibers are examined using cold and warm sensation,
and pinprick. (From Gylfadottir SS, Weeracharoenkul D, Andersen ST, Niruthisard S, Suwan-
walaikorn S, Jensen TS. Painful and non-painful diabetic polyneuropathy: Clinical character-
istics and diagnostic issues. J Diabetes Investig. 2019;10(5):1148-1157.)

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1196 Castater et al

Fig. 5. How to Classify Diabetic Foot Infection? From D-Foot International How to classify
diabetic foot infections. Available at [Link]
info-cards.

Radiography
Diagnostic imaging typically begins with plain radiographs to assess for fracture, foreign
bodies, gas in soft tissues, or signs of osteolytic bone changes suggestive of osteomy-
elitis. Further evaluation can be done with computed tomography (CT) imaging or MRI,
with the latter being the most sensitive and specific for diagnosis of osteomyelitis.56–58

Treatment
Antibiotic therapy
The Infectious Disease Society of America recommends initiating antibiotic treatment
if 2 or more signs of inflammation exist (warmth, erythema, tenderness, pain, indura-
tion, or purulent discharge).59,60 Many patients with mild to moderate infections can be
managed in the outpatient setting with enteral antibiotics,61 whereas those presenting
with deeper wound infections will likely require parenteral antibiotics. Other consider-
ations when determining inpatient versus outpatient management include compliance
and health literacy.62 Another important step in the management of a diabetic foot ul-
cer is staging and classification. The most common classification systems used are
the Wagner and University of Texas Systems,63 both of which assist in assessing
the presence of infection, ulcer depth, and risk of amputation, while the University
of Texas System also identifies the presence of ischemia64 (Tables 2 and 3).

Table 2
Wagner Diabetic Foot Ulcer Grade Classification System (sometimes referred to as Merritt-
Wagner)

0 Intact skin
1 Superficial ulcer
2 Deep ulcer
3 Ulcer with bone involvement
4 Forefoot gangrene
5 Full foot gangrene

Adapted from Wagner FW Jr. The dysvascular foot: a system for diagnosis and treatment. Foot
Ankle. 1981;2(2):64-122; with permission.

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Table 3
University of Texas diabetic foot ulcer classification system

Stage/Grade 0 1 2 3
A Preulcerative or postulcerative Superficial ulcer, noninvolving Ulcer penetrating to tendon Ulcer penetrating to bone or joint
lesion completely epithelialized tendon capsule or bone or capsule
B Infection Infection Infection Infection
C Ischemia Ischemia Ischemia Ischemia
D Infection & ischemia Infection & ischemia Infection & ischemia Infection & ischemia
Score: Grade____Stage____

Diabetic Soft Tissue Infections

Adapted from Lavery LA, Armstrong DG, Harkless LB. Classification of diabetic foot wounds. J Foot Ankle Surg. 1996;35(6):528-531; with permission.

1197
1198 Castater et al

Surgical management
For more severe infections, surgical intervention may be required and can range
from basic incision and drainage to more extensive wound debridement or even
amputation.54 Even though 25% of diabetic foot ulcers that fail to heal will require
amputation,65 aggressive diagnosis and treatment reduce amputation rates.66
Emergent operative management is indicated when signs of sepsis, ischemia,
necrotizing fasciitis, or gas gangrene are present.54 Overall management is
centered on prevention with patient education being the most important preventive
strategy.67–70

CELLULITIS AND ABSCESSES

Epidemiology
Cellulitis is an acute bacterial infection of the dermis and the subcutaneous tissue
that can affect any part of the body, but most commonly occurs in the lower ex-
tremities.71 The most common causes of cellulitis are the following: soft tissue
trauma from puncture wounds or bites, burns, SSI, or secondary infection of exist-
ing skin conditions, such as eczema or venous stasis ulcers. These typically result
from disruption of the skin by some exogenous factor. Less common causes are
extension of a subjacent infection or hematogenous spread from a distant site of
infection.
Risk factors for cellulitis72 include the following:
 Diabetes mellitus
 Immunocompromise
 Peripheral vascular disease
 Lymphedema
 Interstitial edema
 History of irradiation to tissue
Because diabetic patients often develop peripheral vascular disease over time, their
risk of developing cellulitis is increased.

Pathophysiology
Clinical manifestation
A skin abscess is a collection of pus within the dermis or subcutaneous space. It man-
ifests as a painful, fluctuant, erythematous nodule without or without surrounding
cellulitis. Spontaneous drainage of purulent material may occur, and regional adenop-
athy may be seen. Skin abscesses may develop via a deep infection of a hair follicle
(furuncle), where purulent material has extended through the dermis into the subcu-
taneous tissue. Possible predisposing factors include increased friction and perspira-
tion, corticosteroid use, diabetes mellitus, and inherited or acquired defects in
neutrophil function.73,74 Multiple furuncles can coalesce to form carbuncles, where
destruction of fibrous tissue septa and interconnected abscesses are seen (Fig. 6).
For both, S aureus is the most common causative organism. S aureus is frequently
colonized on the skin of patients with diabetes, which contributes to their increased
risk. Ultrasonography or radiographic examination can be useful to ascertain whether
a skin or deeper abscess is present.
Signs and symptoms
Most patients with cellulitis will have the nonnecrotizing form of the disease process.
Patients present with acute pain, erythema, and edema accompanied by constitu-
tional symptoms, such as fever, chills, or malaise (Fig. 7). Physical examination usually

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 Diabetic Soft Tissue Infections 1199

Fig. 6. Folliculitis, boil (furuncle), carbuncle (collection of boils) diagram and image. https://
[Link]/photo/skin-of-woman-with-big-and-painfull-furuncle-medicine-and-
skincare-concept-gm1191905865-338457818?clarity5false. December 08, 2019. Accessed
July 14, 2023. nymphoenix. Large abscess with pus under inflamed skin stock photoID
1338889918. [Link]
skin-gm1338889918-419353277?clarity5false. September 07, 2021. Accessed July 14, 2023.
MicrovOne. Human skin. Layered epidermis with hair follicle, sweat and sebaceous glands.
Healthy skin anatomy medical vector illustration stock illustration ID 1262260786. https://
[Link]/vector/human-skin-layered-epidermis-with-hair-follicle-sweat-and-
sebaceous-glands-healthy-gm1262260786-369328776?clarity5false. :July 29, 2020. Accessed
July 14, 2023. TAK. Image of skin problems, rough skin/acne, early to advanced folliculitis
stock illustration ID 1411956564. [Link]
problems-rough-skin-acne-early-to-advanced-folliculitis-gm1411956564-461587056?clarity5
false. July 31, 2022. Accessed July 14, 2023. Created from: HengDao. Folliculitis stock
photo ID 1332856446. [Link]
415581289?phrase5pimples1folliculitis. August 07, 2021. Accessed July 14, 2023. Alek-
sej Sarifulin. Skin of woman with big and painfull furuncle. Medicine and skincare
concept stock photo ID 1191905865.

shows erythema with advancing borders, tenderness, edema, increased warmth to

touch, or fluctuance. Lymphangitis characterized by an erythematous linear streak
that extends to a draining lymph node basin may be present. Perirectal abscesses
have similar signs and symptoms but are located in the perineal area.

Fig. 7. Presentation of patient with cellulitis.

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1200 Castater et al

Microbiology
Most cellulitis in healthy adults is caused by a single aerobic pathogen, with the 2
most common organisms being Streptococcus pyogenes and Staphylococcus
aureus (Fig. 8). Streptococcus pneumoniae is more common in patients with dia-
betes mellitus, alcoholism, systemic lupus erythematosus, and hematologic malig-
nancies.75 Pseudomonas aeruginosa is a particularly prevalent microorganism in
diabetic infections and is discussed later in this article. Many diabetic infections
can be polymicrobial, especially in the foot. Attempts to isolate a causative pathogen
in general are usually unsuccessful, as needle aspiration and skin biopsy at an
advancing margin of erythema are positive in only 15% and 40% of cases,
respectively.

Treatment
Antibiotic therapy
Cellulitis can usually be treated with empirical antibiotic regimens that include medica-
tions effective against S pyogenes and S aureus. Methicillin-resistant Staphylococcus
aureus (MRSA) can be present in up to 70% of all S aureus infections acquired in the
community76,77 and are more closely associated with diabetic patients. Bacteremia is
uncommon, and only 2% to 4% of all patients with cellulitis will have positive blood
cultures.77,78 For otherwise healthy adults with a diagnosis of uncomplicated, early
cellulitis without systemic manifestations, treatment can be provided with an oral anti-
biotic on an outpatient basis. The most empiric agents are the following: cephalexin,
dicloxacillin, cefadroxil, erythromycin, or clindamycin. When MRSA is suspected,
trimethoprim-sulfamethoxazole or clindamycin is often given. Appropriate analgesic
agents should also be provided for pain control.
Patients that have diabetes mellitus or are immunocompromised, or who have sys-
temic manifestations including high fever/chills or sepsis, rapidly expanding erythema,
or cellulitis refractory to oral antibiotic treatment, should be admitted to the hospital
for intravenous antibiotic therapy. For diabetic patients, ampicillin-sulbactam or
piperacillin-tazobactam should be considered to cover gram-negative organisms.
Vancomycin, linezolid, daptomycin, or tigecycline should be given to patients with
high-risk or confirmed MRSA infections. Although not common, untreated or inade-
quately treated nonnecrotizing cellulitis can progress to necrotizing cellulitis. The diag-
nosis and management of NSTIs are discussed separately in this article.

Fig. 8. Abscess due to community-acquired MRSA.

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 Diabetic Soft Tissue Infections 1201

Surgical management
For fluctuant skin abscesses greater than 2 cm, treatment often consists of providing
an antibiotic regimen and performing an incision and drainage procedure. A thorough
search for loculated areas should be undertaken once the abscess cavity is unroofed
to facilitate adequate drainage. The incision must be large enough to prevent prema-
ture closure and recurrence of the abscess. Culture of debrided material should be
considered for patients with diabetic mellitus given higher presence of polymicrobial
infection. For skin abscesses less than 2 cm that are spontaneously draining, close
observation is an acceptable alternative. Although needle aspiration is less invasive,
it is not recommended to perform needle aspiration of abscess contents unless the
abscess is on the breast.73,74

NECROTIZING SOFT TISSUE INFECTIONS

Epidemiology
NSTIs are aggressive infections that can be difficult to recognize and diagnose but are
rapidly progressive and are associated with high morbidity and mortality. These risks
are drastically increased in patients who present in shock, are elderly, or are immuno-
compromised.79,80 It is important for the evaluating physician to maintain a high index
of suspicion for NSTIs, as early intervention with broad-spectrum antibiotics and sur-
gical debridement has been consistently shown to improve survival.81

Pathophysiology
NSTIs are classified into 4 types, based on the pathogen of the underlying infection.
Each has different features and predicted mortality. Type I NSTIs are the most com-
mon type of infection, are polymicrobial, and involve both aerobic and anaerobic bac-
teria.79,80 Type II NSTIs are monomicrobial, with the most common pathogen being
group A streptococcus. Less common are NSTIs caused by Clostridium and Vibrio,
which fall under type III infections, and Aeromonas and fungi, which are found in
type IV infections (Table 4).
Regardless of the pathogen causing the NSTI, the hallmark of these infections in-
volves necrosis caused by bacterial toxins leading to cytokine activation, local
thrombosis, and ischemia.80 The resultant ischemia leads to further spread of the
inciting pathogen, which leads to a cycle of further dissemination of infection with
the potential for widespread disease (Fig. 9). It is the release of endotoxins and exo-
toxins by the causative pathogen that leads to the systemic illness often seen in
NSTIs.
Clinical manifestation
The clinical presentation of NSTI can often be subtle and in approximately 50% of
patients does not involve traumatic inoculation of the underlying bacteria.82,83 Mani-
festations of NSTIs that are not associated with an open injury are often more subtle
than those that are caused by traumatic inoculation. In the early stages of infection,
patients present with pain and mild systemic symptoms. Cutaneous manifestations
may include erythema (which can be mistaken for a simple cellulitis), bullae, skin ne-
crosis, and/or local anesthesia83,84 (Figs. 10 and 11).
Pain out of proportion to clinical findings, or pain extending beyond physical exam-
ination findings, should lead to a higher clinical suspicion for an underlying NSTI. It is
very important to remember that even with more advanced disease, patients may pre-
sent with varying severity of sepsis and without any notable physical examination find-
ings.84 In addition, lack of sensation can seem to be a reassuring symptom but may
actually be a late finding when extensive necrosis destroys peripheral nerve fibers.

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 1202
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Castater et al
Table 4
Features of type I to IV necrotizing soft tissue infections

Types Organisms Population Cause Features Mortality

Type I (70%–80%) Polymicrobial Multiple comorbidities Polymicrobial, bowel flora More indolent, better Variable depending on
prognosis comorbidities
Type II (20%–30%) Group A strep Young, often healthy, Trauma, bites, IVDU Aggressive, frequently >30%
(S aureus, MRSA) intravenous drug user missed,  toxic shock
(IVDU) syndrome
Type III (rare) Monomicrobial Seafood ingestion, water 30%–40%
(vibrio, clostridium) contamination
Type IV (rare) Fungal (Candida, Immunocompromised Trauma (wounds, bones) Aggressive >50%
Zygomycetes)
 Diabetic Soft Tissue Infections 1203

Fig. 9. Continuous dissemination cycle of NSTIs.

Diagnosis of NSTIs mostly relies on clinical findings. It is crucial for the provider to
maintain a high index of suspicion when working up a patient for NSTI. When the diag-
nosis is unclear, the adjuncts listed in later discussion may help the physician make a
diagnosis and initiate treatment. The authors want to emphasize that if there is any
concern, prompt surgical intervention, which can include bedside cut-down, is war-
ranted to rule out potentially rapidly progressing and life-threatening infection.

Laboratory workup
The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was initially
created to allow physicians to detect NSTIs before the progression of the infection,
as clinical signs are often subtle.79 As noted above, physical examination findings
may not correlate with severity of underlying infection. Therefore, the LRINEC score
can be used to support clinical findings and aid in the diagnosis of an underlying
NSTI81 (Table 5). Importantly, the utility of the LRINEC score is supportive only
because studies evaluating its sensitivity and specificity vary widely.79 It is imperative
that the physician not rely on a negative score to rule out NSTI, particularly if clinical
suspicion remains high.81,85 In particular, the LRINEC score’s positive predictive value
to diagnose NSTI is even less reliable in patients with diabetes, who already have a
higher risk of morbidity and mortality with delayed treatment.79

Fig. 10. Left lower extremity with edema, hemorrhagic bullae, and skin necrosis with foul-
smelling discharge.

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1204 Castater et al

Fig. 11. Clinical presentation of perineal necrotizing soft tissue infection.

Radiography
Both plain film and axial imaging can be used in conjunction with physical examination
findings to support the diagnosis of an NSTI. In the hemodynamically unstable patient,
plain film imaging may be useful to quickly identify gas or edema within the soft tissue8
(Fig. 12). CT or MRI may show decreased enhancement, edema, or air along the
fascial planes80,83 but obtaining them may delay treatment. The absence of positive
CT or MRI findings does not rule out a necrotizing infection and may delay initiation
of treatment.83

Treatment
Once an NSTI is diagnosed, rapid initiation of treatment is crucial to successful man-
agement of NSTIs, as the rates of morbidity and mortality, intensive care unit, and hos-
pital length of stays have been shown to decrease when surgical intervention is
rapid.81,86 The hallmarks of treatment for NSTIs involve both broad-spectrum anti-
biotic therapy and operative debridement.

Antibiotic therapy
Initial antibiotic therapy in patients in whom an NSTI is suspected should be broad to
cover both aerobic and anaerobic activity, as well as MRSA, and can be narrowed
based on cultures and sensitivities. Guidelines recommend empiric treatment with
vancomycin, linezolid, or daptomycin, along with piperacillin-tazobactam, a carbape-
nem, or ceftriaxone with metronidazole, or a fluoroquinolone with metronidazole.83
The addition of clindamycin also aids to suppress toxin-mediated cytokine production
caused by group A streptococci.

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 Diabetic Soft Tissue Infections 1205

Table 5
The laboratory risk indicator for necrotizing fasciitis

Variable Score
C-reactive protein
<15 0
15 4
Total WBC (1000 per mm3)
<15 0
15–25 1
>25 2
Hemoglobin (g/dL)
>13.5 0
11–13.5 1
<11 2
Sodium (mmol/L)
135 0
<135 2
Creatinine (mg/dL)
1.59 0
>1.59 2
Glucose (mg/dL)
<180 0
180 1

Adapted from Wong CH, Khin LW, Heng KS, Tan KC, Low CO. The LRINEC (Laboratory Risk Indicator
for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue
infections. Crit Care Med. 2004;32(7):1535-1541; with permission.

Surgical management
Although rapid initiation of antibiotic therapy is crucial, early surgical intervention and
debridement of infected tissue is the key to successful management of the infection
and improvement of survival.82 Operative management is geared toward achieving
source control by aggressive removal of infected and necrotic tissue (Fig. 13). Multiple
debridements are often required to ensure true control of the infection, and progres-
sive infection can often be seen during serial debridements80 (Fig. 14). Once adequate
control of the infection has been achieved, large disfiguring wounds can be managed
using an interdisciplinary approach for appropriate tissue coverage.80
Perioperative care
Severe NSTIs often lead to severe systemic illness and multiorgan failure. The periop-
erative management in these patients is an important component of management.
Close monitoring and management of a patient’s hemodynamic status, frequent
and careful serial examinations of wounds, strict glucose control and early nutritional
support are all important adjuncts to management.81 Rapid treatment of systemic dis-
ease, such as shock, respiratory or renal failure, is also key to survival.84

PSEUDOMONAS INFECTIONS
Epidemiology
P aeruginosa infections complicate DFIs. Although the presentation can vary, classic
physical examination findings include a blue-green hue or the presence of Erythema

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1206 Castater et al

Fig. 12. Evidence of air tracking along the leg on coronal CT images of the right lower
extremity.

Fig. 13. Necrotic tissue should be debrided back to healthy, viable, bleeding tissue.

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 Diabetic Soft Tissue Infections 1207

Fig. 14. Serial debridements occur until no infection remains and attention can be turned to
closure of the defect.

Gangrenosum.87 Diagnosis relies on blood and tissue cultures. Treatment largely de-
pends on a multipronged antimicrobial approach given its high rate of drug resistance
and tapering of antibiotics as soon as clinically possible.
Pseudomonas remains a challenging diagnosis in the setting of diabetic infections.
Pseudomonas is a gram-negative, flagellated, aerobic rod that is both catalase and
oxidase positive.88 It can grow in water and soil as well as on animals and plants.
Although Pseudomonas strains are not the most common organism in DFIs, P aerugi-
nosa specifically is the most common and virulent strain of Pseudomonas that occurs
in DFIs. Pseudomonas most commonly occurs in the setting of polymicrobial infec-
tions and portends a poor prognosis as compared with DFIs without pseudomonal
inoculation.88,89 DFIs with P aeruginosa account for roughly 10% to 30% of all diabetic
foot wounds89,90 (Fig. 15).
Risk factors for pseudomonal infections88 include the following:
 Smoking
 Failure of outpatient antibiotic treatment for DFI within the past 90 days
 Advanced age
 Immunocompromised

Clinical Manifestation
The diagnosis of Pseudomonal infection in DFIs requires high clinical suspicion and an
astute physical examination. Skin infection of Pseudomonas can occur owing to direct

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1208 Castater et al

Fig. 15. Clinical examples of pseudomonal foot wounds. (Left) Nedomacki/iStock/Getty

Images. (Right) Dr_Microbe/iStock/Getty Images.

organism inoculation in a wound or secondary seeding from a bacteremia.89–91

Pseudomonas creates blue-green pigments owing to its creation of pyocyanin and
pyoverdine.92 Although wounds infected with Pseudomonas can have a blue-green
hue or purulence, not all wounds infected with Pseudomonas will have this finding.92

Laboratory workup
An elevated ESR, as well as leukocytosis, more commonly occurs with pseudomonal
DFIs, whereas ESR may not be elevated with other microbial infections.
Ecthyma Gangrenosum is a common manifestation of Pseudomonas infection and
is characterized by erythematous nodules or hemorrhagic bullae that then progress
into necrotic ulcers with eschar formation.88,93 Interestingly, this can occur both
with and without the presence of Pseudomonas bacteremia. If bacteremia is present,
there are often multiple lesions in different locations that can be identified on physical
examination. In the absence of bacteremia, there is typically one wound due to direct
inoculation. Tissue culture, in addition to blood culture, is necessary to make this diag-
nosis. Histopathology of Ecthyma Gangrenosum reveals necrotic vasculitis with
vascular thrombosis and may reveal gram-negative rods along the adventitia of the
blood vessels88 (Fig. 16).

Treatment
Antibiotic therapy
Treatment of pseudomonal DFIs is a challenging effort. The prevalence of multidrug-
resistant P aeruginosa makes treatment increasingly difficult.88 There are many

Fig. 16. Clinical appearance of Ecthyma Gangrenosum.

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 Diabetic Soft Tissue Infections 1209

mechanisms identified in the cause of drug resistance. P aeruginosa is known to form

early (<24 hour) biofilms more so than other bacterial species, especially in DFIs.94–96
In addition, it has shown beta-lactamase and amp-C cephalosporinase activity
against multiple generations of cephalosporins and carbapenems.88,95 Many pseudo-
monal strains carry several aminoglycoside-modifying enzymes, acting on different
aminoglycoside substituents, rendering them all ineffective.88,94 Furthermore, P aeru-
ginosa can secrete toxins, promote membrane impermeability and porin alteration,
and perform quorum sensing, all of which contribute to drug resistance. These mech-
anisms allow Pseudomonas to evade the immune system and antimicrobials.88,92
Mainstays of antipseudomonal antibiotic therapy are combination therapy with an
antipseudomonal beta-lactam, carbapenem, and fluoroquinolone, such as piperacil-
lin/tazobactam, ceftazidime/avibactam, cefepime, or meropenem.88,95 Ceftolozane/
tazobactam can be used in extreme drug-resistant Pseudomonas infection.97 As al-
ways, narrowing antibiotics based on culture susceptibility as soon as possible is of
the utmost importance given the high rates of antibiotic resistance by this organism
in particular. Antibiotic duration is typically 10 to 14 days.97 If deep space infection
is suspected, or an underlying abscess is formed, surgical debridement may be
necessary. Rarely will Pseudomonas cause a necrotizing infection.

COMPLICATIONS OF PUNCTURE WOUNDS

Epidemiology
Puncture wounds are common injuries with self-limiting symptoms in many cases.
Many individuals never seek care following puncture wounds, so the true incidence
of puncture wounds is unknown.98 These wounds may occur in any location, but
the plantar surface of the feet, the palmar surface of the hands, and the fingertips
are most commonly affected (Fig. 17). Nails are the most common source of puncture
injuries, but glass, wood, and other metal objects can frequently cause these
wounds.98–100 Although their course can be relatively benign most of the time, the
sequelae of puncture wounds can also include serious complications with the poten-
tial for limb loss and death. Cellulitis, foreign body granuloma, abscess, osteomyelitis,
septic arthritis, NSTIs, tenosynovitis, and sepsis are a few of the serious morbidities
that can result from puncture wounds.

Fig. 17. Clinical appearance of puncture wound. Jim Still-Pepper/iStock/Getty Images.

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1210 Castater et al

Pathophysiology
Microbiology
The most common gram-positive organisms isolated from puncture wounds are S
aureus, Staphylococcus epidermidis, and alpha-hemolytic streptococci. Gram-
negative organisms include P aeruginosa, Escherichia coli, Proteus, and Klebsi-
ella.101,102 Diabetic patients generally develop polymicrobial infections.101 Extensive
variability exists based on the setting where the injury occurs. Water, soil, and farm
exposures add a significant number of possible infecting organisms. Fungal and
mycobacterial infections following puncture wound injury have also been
reported.102,103
Pseudomonal infections are of particular importance in plantar puncture wounds.
Pseudomonas is the most common organism causing osteomyelitis after puncture
wounds.99,104,105 Several investigators have hypothesized that this occurs when a
puncture wound occurs through shoes harboring Pseudomonas. This hypothesis is
supported by positive pseudomonal cultures taken from patients’ shoes following
punctures that progress to osteomyelitis.96,101,106–110

Clinical Manifestation
The clinical course of puncture wounds depends on multiple factors, including pa-
tient comorbidities, immunosuppression, depth of injury, type and degree of
contamination, presence of a retained foreign body, and time to presentation.
The authors do not know the exact impact each of these factors has, largely
because so many patients do not seek medical care following injury. Not surpris-
ingly, diabetic patients have more complications and more serious morbidity
following puncture wounds. Truong and colleagues104,105 evaluated 114 consecu-
tive patients with a foot infection following puncture wounds and found that greater
than 70% of the patients presenting with infections following puncture wounds
were diabetic. In looking at the hospital course for these 114 patients, they found
that diabetic patients had a higher surgery rate, had more surgeries, were 14 times
more likely to undergo amputation, and were 9 times more likely to develop oste-
omyelitis compared with nondiabetic patients. Numerous studies have shown that
there is an association between a higher infection rate and delayed presentation
greater than 24 hours from the time of injury.111,101 This is confounded by the
fact that a patient not immediately seeking care may only present once signs of in-
fections develop. Despite this possible confounding factor, later presentation is still
a predictor for a worse outcome.

Treatment
Antibiotic therapy
For puncture wounds that do not appear infected, it is important to confirm the
patient’s tetanus immunization status and administer tetanus vaccine or booster as
indicated.112 Irrigation and local wound care may be performed without prophylactic
antibiotics for these wounds. Infected puncture wounds should be treated swiftly with
appropriate laboratory studies, imaging, antibiotic therapy, and surgical source con-
trol as indicated by the specific characteristics of the wound and patient comorbid-
ities. All patients presenting with puncture wounds should be evaluated for the
presence of a foreign body at the site of injury. Foreign bodies should be removed,
as they confer higher risk of complications. The specifics of the object, puncture loca-
tion, and depth should dictate whether this is performed in the operating room or at the
bedside.

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 Diabetic Soft Tissue Infections 1211

CLINICS CARE POINTS

 Because diabetes is a risk factor for the development of many soft tissue infections, a high
index of suspicion should be maintained when evaluating these patients, and prompt
surgical treatment is needed for more severe wounds.
 Necrotizing soft tissue infections can be life-threatening infections that progress rapidly
especially in diabetic patients. Workup should not precede operative intervention when
clinical suspicion is high.

DISCLOSURE

The authors have nothing to disclose.

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