ALG Diabetic Foot 505
• A n earlier and commonly used classification
BASIC INFORMATION
DEFINITION
Diabetic foot infections (DFIs) are a common
and potentially serious problem in persons with
diabetes. They usually arise from either a skin
ulceration that occurs secondarily to peripheral
neuropathy or in a wound caused by some form
of trauma. The infection usually involves one or
more bacteria and can spread to contiguous tis-
sues including bone, causing an osteomyelitis.
SYNONYMS
Diabetic foot ulcer
Diabetic foot infection
DFI
ICD-10CM CODES
E11.621 Type 2 diabetes mellitus with foot
ulcer
E10.5 Diabetes mellitus with peripheral
circulatory complications
E10.6D Diabetes mellitus with other
specific complications
EPIDEMIOLOGY &
DEMOGRAPHICS
INCIDENCE: DFIs are the most common cause
of hospitalizations for diabetic patients. They
account for 20% of all hospital admissions.
Nearly one in six patients will die within 1 yr of
their infection.
PREVALENCE: 25 million people in the U.S.
have diabetes, of which 19% to 34% will
develop a foot ulcer in their lifetime, and more
than 50% of these will become infected.
PREDOMINANT SEX & AGE: Females greater
than males
PEAK INCIDENCE: More common in Hispanics,
African Americans, and Native Americans due to
increased rates of diabetes in those populations
RISK FACTORS:
• Diabetes greater than 10 yr
• Poor glucose control
• Peripheral neuropathy: Altered protective
sensation and altered pain response
• Diabetic angiopathy: Atherosclerotic obstruc-
tion of larger vessels leading to peripheral
vascular disease
• Evidence of increased local pressure: Callus
or erythema
PHYSICAL FINDINGS & CLINICAL
PRESENTATION
• Based on guidelines by Infectious Diseases
Society of America, infection is present if
obvious purulent drainage and/or the pres-
ence of two or more signs of inflammation:
1. Erythema
2. Pain
3. Tenderness
4. Warmth
5. Induration
• Systemic signs of infection include:
1. Anorexia, nausea/vomiting
2. Fever, chills, night sweats
3. Change in mental status and recent wors-
ening of glycemic control
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system was originally proposed by Wagner
(Table 1).
• An update to the Wagner system was
introduced at the University of Texas (UT),
San Antonio (Table 2), U.S. While similar to
Wagner in its first three categories, this later
system eliminated grades 4 and 5 and added
stages A-D for each of the grades. The UT
system was the first diabetic foot ulcer clas-
sification to be validated. University of Texas
system Grade:
• Grade 0: Pre- or postulcerative (Stages A to D)
• Grade 1: Full-thickness ulcer not involving
tendon, capsule, or bone (Stages A to D)
• Grade 2: Tendon or capsular involvement
without bone palpable (Stages A to D)
• Grade 3: Probes to bone (Stages A to D)
Stage:
1. A: Noninfected
2. B: Infected
3. C: Ischemic
4. D: Infected and ischemic
ETIOLOGY
• Most diabetic foot infections are polymicro-
bial (can involve 5 to 7 different bacteria) and
depend on the extent of involvement.
• Superficial infections are likely due to gram-
positive skin bacteria:
1. Staphylococcus aureus, includes methicillin-
resistant S. aureus (MRSA)
2. Streptococcus agalactiae (group B strep-
tococcus) and Streptococcus pyogenes
(group A streptococcus)
3. Coagulase-negative Staphylococcus
• Infections that are deep, chronically infected,
or previously treated are likely to be
polymicrobial:
1. Include above bacteria plus entero-
cocci, gram-negative rods including
Pseudomonas aeruginosa and anaerobes
2. With gangrene can expect more anaerobic
bacteria such as Clostridia and Bacteroides
species
3. Patients with multiple admissions can
have more resistant bacteria such as
ESBL-type resistant gram-negative rod
bacteria, MRSA, and Acinetobacter
TABLE 1 Wagner Diabetic Foot
Ulcer Classification System
Grade Description
0 No ulcer, but high-risk foot (e.g.,
deformity, callus, insensitivity)
1 Superficial full-thickness ulcer
2 Deeper ulcer, penetrating tendons, no
bone involvement
3 Deeper ulcer with bone involvement,
osteitis
4 Partial gangrene (e.g., toes, forefoot)
5 Gangrene of whole foot
Modified from Oyibo S et al: A comparison of two diabetic foot
ulcer classification systems: the Wagner and the University
of Texas wound classification systems, Diabetes Care
24:84-88, 2001. In Melmed S et al: Williams textbook of
endocrinology, ed 14, Philadelphia, 2020, Elsevier.
DIAGNOSIS D
DIFFERENTIAL DIAGNOSIS
Other inflammatory conditions that can mimic
diabetic foot infections include:
• Crystal-associated arthritis such as gout
• Trauma
• Acute Charcot arthropathy from long-standing
diabetes
• Venous stasis ulcers
• Deep vein thrombosis
and Disorders
Diseases
WORKUP
Evaluation of a patient with a DFI involves
determining the extent and severity of the
infection, identifying the underlying factors that
predispose to the infection, and determining
the microbiologic etiology. An algorithm for risk
screening in the diabetic foot is illustrated in
I
Fig. 1.
PHYSICAL EXAMINATION
• Vital signs: Fever, chills, hypotension, tachy-
cardia can be present.
• Detailed wound description: Length, width,
and depth of wound, consistency of drainage,
character of wound base: Granular fibrous
necrotic.
• Determination of osteomyelitis: Highly likely if
bone visible. A positive probe test to bone has
a sensitivity of 66% and specificity of 85% in
diagnosing bone infection.
• Necrotizing infections may present with cuta-
neous bullae, soft tissue gas, foul odor, and
skin discoloration (Fig. E2).
• Severe infections may present with gan-
grene, tissue necrosis, and evidence of tissue
ischemia (Fig. E3), all of which may be limb
threatening.
LABORATORY TESTS
Important to obtain at baseline and to assess
response to therapy:
• Fewer than 50% of patients have an elevated
WBC.
• Determine BUN/Cr, acidosis, hemoglobin A1C,
and blood sugar.
• Acute phase reactants: Sed rate and CRP are
markers for inflammation.
1. Sed rate >70 increases probability of bone
infection.
• Serum prealbumin and albumin are markers
for nutritional status and ability to heal.
• An ulcer size larger than 2 cm2 is indicative
of osteomyelitis.
• Gram stains and cultures: Superficial cultures
should not be obtained as they may con-
tain colonizing bacteria; instead deep tissue
cultures (aerobic and anaerobic) should be
obtained.
IMAGING STUDIES
• Plain film x-ray evaluates bones and soft tis-
sues and can detect presence of tissue gas,
which would represent an emergent situation
(Fig. 4).
• Osteomyelitis appears as radiolucencies,
periosteal reaction, and destructive changes.
506 Diabetic Foot ALG

TABLE 2 University of Texas Wound Classification System

Stage Grade 0 Grade 1 Grade 2 Grade 3
A Preulcer or postulcer lesion; no skin break Superficial ulcer Deep ulcer to tendon or capsule Wound penetrating bone or joint
B + Infection + Infection + Infection + Infection
C + Ischemia + Ischemia + Ischemia + Ischemia
D + Infection and ischemia + Infection and ischemia + Infection and ischemia + Infection and ischemia

Modified from Armstrong DG et al: Validation of a diabetic wound classification system. The contribution of depth, infection, and ischemia to risk of amputation, Diabetes Care 12:855-859, 1998. In
Melmed S et al: Williams textbook of endocrinology, ed 14, Philadelphia, 2020, Elsevier.

Diabetic patient anaerobes, and Staphylococcus aureus.

Risk factors for ulceration?
• Peripheral neuropathy
• Peripheral vascular disease
• Foot deformity
• Edema
• Past ulcer history
• Other complications
No risk factor
Provide general advice
• Nail care, hygiene
• Footwear
• Podiatry
Review risk status
at least annually
FIG. 1 Simple algorithm for risk screening in the diabetic foot. (From Melmed S et al: Williams textbook
of endocrinology, ed 14, Philadelphia, 2020, Elsevier.)
Plain films are 67% specific and 60% sensi-
tive for osteomyelitis.
• Bone scan: Indium-111 or technetium-99
can distinguish acute and chronic infections.
• CT and MRI: MRI is the most sensitive and
specific test to detect osteomyelitis and
abscess formation.
OTHER DIAGNOSTIC TESTS
• Annual noninvasive vascular studies: Ankle
brachial index (ABI): <0.90 or >1.30 indi-
cates peripheral arterial disease
• Transcutaneous oxygen (TcPO2) tension
measurements: Predictive of wound healing
failure at levels below 25 mm Hg
TREATMENT
Empiric antibiotic regimen should be started
based on likely pathogens suspected and
severity of disease. Wound management
and debridement including surgical consultation
are important as well.
NONPHARMACOLOGIC THERAPY
• Good nutrition will promote wound healing.
• Glycemic control will promote healing.
• Fluid and electrolyte balance will improve
healing.
Adjust dose based on CrCl.
2. Meropenem: 1 g IV q8h with normal kid-
ney function has comparable coverage
as piperacillin-tazobactam. Similar agents
include imipenem and doripenem.
3. Third-generation cephalosporin such as
cefepime, 2 g IV q8h, or ceftriaxone, 2
g IV qd, have excellent gram-negative
coverage, and for anaerobic coverage
add metronidazole, 500 mg IV q8h, or
clindamycin 900 mg IV q8h. Cefepime
will cover Pseudomonas aeruginosa, but
Yes risk factor ceftriaxone will not.
4. For penicillin-allergic patients a combina-
tion of ciprofloxacin, 400 mg IV q12h, plus
• Foot care education metronidazole or clindamycin is an option.
• Regular podiatry Aztreonam is another option for gram-
• Possible special negative rod coverage, 2 g IV q8h.
footwear, hosiery, etc. 5. If MRSA is suspected, need to add IV
vancomycin, 15 to 20 mg/kg IV q8 to 12h,
depending on age and CrCl and follow
Much more frequent review, trough levels to keep above 15. Other
always inspecting feet options include daptomycin, 4 mg/kg IV
qd, which does not have to be adjusted for
CrCl, or linezolid, 400 to 600 mg IV q12h.
6. If VRE is suspected, options include tige-
cycline, 100-mg IV load dose, then 50-mg
ACUTE GENERAL TREATMENT IV q12h, which also covers MRSA and
WOUND MANAGEMENT: gram-negative rods but not Pseudomonas
• Debridement of callus and necrotic tissues aeruginosa, or can use daptomycin or
by wound care specialist or surgeon and at linezolid.
times may require multiple debridements. 7. If ESBL gram-negative bacteria are sus-
• Wound dressing: To absorb exudates and pected, then options include meropenem
promote healing. Many products are avail- or ertapenem, 1 g IV qd, or tigecycline.
able, but none has been proven superior and 8. Once culture results are known can tailor
include: antibiotics to more specific agent.
1. Enzymes • Oral antibiotics used for milder infections
2. Gels include amoxicillin-clavulanate, 875 mg PO
3. Hydrocolloids q12h, which will cover gram-negative rods,
4. Antiseptics containing iodine or silver salts streptococci, and anaerobes, or ciprofloxacin
5. Honey plus metronidazole or clindamycin. Bactrim
• Relieve pressure on the foot: Casts or special will cover MRSA and MSSA and some gram-
shoes. negative rods.
• Amputation or revascularization procedures The expert panel on diabetic foot infection
(DFI) of the International Working Group on the
such as angioplasty or bypass grafting may
be necessary. Diabetic Foot conducted a systematic review.
ANTIBIOTIC MANAGEMENT: Results of comparisons of different antibiotic
• Prior to receiving culture results an empiric regimens generally demonstrated that newly
antibiotic regimen should be started as soon introduced antibiotic regimens appeared to be
as possible to cover skin bacteria, gram- as effective as conventional therapy.
negative rods, and anaerobes. Options for
intravenous therapy include: CHRONIC TREATMENT
1. Piperacillin-tazobactam: 3.375 g IV • Length of therapy: Highly variable depending
q6h with normal kidney function. Will on the severity of the infection. In general,
cover gram-negative rods including 2 to 4 wk of antibiotics is sufficient. If bone
Pseudomonas aeruginosa, streptococci, infection suspected or documented, may

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Diabetic Foot 506.e1

FIG. E2 Foot. Severe diabetic foot infection with significant tissue swelling and necrosis.

FIG. E3 Diabetic foot complication. Oblique radiograph of the foot shows extensive vascular calcification.
There is gas in the soft tissues of the great toe; this more commonly occurs because of air forced in through
an open ulcer than a gas-forming organism infection. The loss of soft tissue around the great toe indicates
ischemic mummification of the toe.

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FIG. 4 X-ray. Significant soft tissue swelling in
midfoot with numerous gas bubbles seen in the
soft tissues.
need 4 to 8 wk of antibiotics, preferably intra-
venous via a peripherally inserted central line
(PICC line).
• Surgical debridement may also be necessary
for several weeks.
COMPLEMENTARY MEDICINE
• Hyperbaric oxygen (HBO): Used as an
adjunct to antibiotics, debridement, and
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ALG Diabetic Foot 507
revascularization in the therapy of chronic, the risk for a patient with diabetes without a
nonhealing wounds associated with diabetes.
Evidence of effectiveness is conflicting. HBO
foot ulcer. D
acts by: REFERRAL
1. Inducing vasoconstriction and reducing • Infectious disease consultant for antibiotic
vasogenic edema management
2. Facilitating fibroblast activity, angiogen- • Surgeon or wound care center for surgical
esis, and wound healing treatments
3. Killing anaerobic bacteria and augmenting • Endocrinologist for good diabetes care
neutrophil bactericidal activity • Vascular surgeon for angioplasty or bypass
• Negative pressure wound therapy (wound procedures
vac): Controlled, subatmospheric pressure
applied to an open wound can accelerate
and Disorders
Diseases
healing and closure.
PEARLS &
1. An open cell foam insert is cut to fit the CONSIDERATIONS
open wound and then secured under a
clear, vapor-permeable, plastic dressing. • In a metaanalysis of randomized controlled
2. Tubing extends from the sponge to a dis- trials on the outcome of DFIs, there was a
22.7% treatment failure rate.
posable collection canister.
3. A portable pump applies 125 mm Hg of • Patients should be advised to seek prompt I
controlled suction to the system. The sub- medical attention as these infections can
atmospheric pressure (suction) is equally progress rapidly to gangrene.
distributed across the open wound and
evacuates stagnant fluid from the wound. SUGGESTED READINGS
DISPOSITION Available on the eBook. See ad in front of
• Following up on sed rates, CRP, BUN/CR, and book for details.
levels of vancomycin if that antibiotic used.
• Surgical or wound center care follow-up. AUTHOR: Glenn G. Fort, MD, MPH
• HBO usually involves multiple sessions over
several weeks.
• Wound vac is applied for weeks and requires
periodic nursing follow-up.
• The risk of death at 5 yr for a patient with a
diabetic foot ulcer is 2 to 5 times as high as
Diabetic Foot 507.e1

SUGGESTED READINGS
Adam A et al: Grainger and Allison’s diagnostic radiology, ed 6, Philadelphia, 2015,
Elsevier. In Grant LA: Grainger & Allison’s diagnostic radiology essentials, ed 2,
Philadelphia, 2019, Elsevier.
Armstrong D et al: Diabetic foot ulcers and their recurrence, N Engl J Med
376:2367-2375, 2017.
Frykberg RG et al: A multinational, multicenter, randomized, double-blinded,
placebo-controlled trial to evaluate the efficacy of cyclical topical wound oxy-
gen therapy (TWO2) in the treatment of chronic diabetic foot ulcers: the TWO2
study, Diabetes Care 43(3):616-624, 2020.
Hart T et al: Management of diabetic foot, JAMA 318(14):1387-1388, 2017.
Hobizal K, Wukich D: Diabetic foot infections: current concept review, Diabet Foot
Ankle 3(10), 2012. http://3402/dfa.v3i0.18409.org.
Lipsky BA et al: Infectious Diseases Society of America clinical practice guideline
for the diagnosis and treatment of diabetic foot infections, Clin Infect Dis
54(12):e132-e173, 2012.
Peters EJ et al: Interventions in the management of infection in the foot in diabe-
tes: a systematic review, Diabetes Metab Res Rev 32(Suppl 1):145-153, 2016.
Santema KTB et al: Hyperbaric oxygen therapy in the treatment of ischemic
lower-extremity ulcers in patients with diabetes: results of the Damocles mul-
ticenter randomized clinical trial, Diabetes Care 41:112, 2018.

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