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Basic Information ⬇

AUTHOR: Glenn G. Fort, MD, MPH

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 tissues including bone, causing an osteomyelitis.

Synonyms

Diabetic foot ulcer

Diabetic foot infection

DFI

ICD-10CM CODES
E11.621Type 2 diabetes mellitus with foot ulcer
E10.5Diabetes mellitus with peripheral circulatory complications
E10.6DDiabetes 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 obstruction 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 presence 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 worsening of glycemic control
  • An earlier and commonly used classification 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 classification 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)

TABLE 2 University of Texas Wound Classification System

StageGrade 0Grade 1Grade 2Grade 3
APreulcer or postulcer lesion; no skin breakSuperficial ulcerDeep ulcer to tendon or capsuleWound 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.

TABLE 1 Wagner Diabetic Foot Ulcer Classification System

GradeDescription
0No ulcer, but high-risk foot (e.g., deformity, callus, insensitivity)
1Superficial full-thickness ulcer
2Deeper ulcer, penetrating tendons, no bone involvement
3Deeper ulcer with bone involvement, osteitis
4Partial gangrene (e.g., toes, forefoot)
5Gangrene 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.

Stage:

  • A: Noninfected
  • B: Infected
  • C: Ischemic
  • D: Infected and ischemic
Etiology

  • Most diabetic foot infections are polymicrobial (can involve five to seven 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 streptococcus) 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 enterococci, 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

Diagnosis ⬆ ⬇

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
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 Fig. 1.

Figure 1 Simple algorithm for risk screening in the diabetic foot.

!!flowchart!!

From Melmed S et al: Williams textbook of endocrinology, ed 14, Philadelphia, 2020, Elsevier.

Physical Examination

  • Vital signs: Fever, chills, hypotension, tachycardia 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 cutaneous bullae, soft tissue gas, foul odor, and skin discoloration (Fig. E2).
  • Severe infections may present with gangrene (Fig. E3), tissue necrosis, and evidence of tissue ischemia (Fig. E4), all of which may be limb threatening.

Figure E2 Foot.

Severe diabetic foot infection with significant tissue swelling and necrosis.

Figure E3 Diabetic gangrene.

From Micheletti RG et al: Andrews’ Diseases of the skin, clinical atlas, ed 2, Philadelphia, 2023, Elsevier.

Figure E4 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.

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 contain colonizing bacteria; instead deep tissue cultures (aerobic and anaerobic) should be obtained.
Imaging Studies

  • Plain film x-ray evaluates bones and soft tissues and can detect presence of tissue gas, which would represent an emergent situation (Fig. 5).
  • Osteomyelitis appears as radiolucencies, periosteal reaction, and destructive changes. Plain films are 67% specific and 60% sensitive 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.

Figure 5 X-ray.

Significant soft tissue swelling in midfoot with numerous gas bubbles seen in the soft tissues.

Other Diagnostic Tests

  • Annual noninvasive vascular studies: Ankle brachial index (ABI): <0.90 or >1.30 indicates 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.
Acute General Treatment
Wound Management

  • Debridement of callus and necrotic tissues by wound care specialist or surgeon and at times may require multiple debridements.
  • Wound dressing: To absorb exudates and promote healing. Many products are available, but none has been proven superior and include:
    1. Enzymes
    2. Gels
    3. Hydrocolloids
    4. Antiseptics containing iodine or silver salts
    5. Honey
  • Relieve pressure on the foot: Casts or special shoes.
  • Amputation or revascularization procedures such as angioplasty or bypass grafting may be necessary.
Antibiotic Management

  • Prior to receiving culture results an empiric antibiotic regimen should be started as soon as possible to cover skin bacteria, gram-negative rods, and anaerobes. Options for intravenous therapy include:
    1. Piperacillin-tazobactam: 3.375 g IV q6h with normal kidney function. Will cover gram-negative rods including Pseudomonas aeruginosa, streptococci, anaerobes, and Staphylococcus aureus. Adjust dose based on CrCl.
    2. Meropenem: 1 g IV q8h with normal kidney 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 ceftriaxone will not.
    4. For penicillin-allergic patients a combination of ciprofloxacin, 400 mg IV q12h, plus metronidazole or clindamycin is an option. Aztreonam is another option for gram-negative rod coverage, 2 g IV q8h.
    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 through levels to keep above 15. Other 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 tigecycline, 100-mg IV load dose, then 50-mg IV q12h, which also covers MRSA and gram-negative rods but not Pseudomonas aeruginosa or can use daptomycin or linezolid.
    7. If ESBL gram-negative bacteria are suspected, then options include meropenem or ertapenem, 1 g IV qd.
    8. Once culture results are known, can tailor antibiotics to more specific agent.
  • Oral antibiotics used for milder infections include amoxicillin-clavulanate, 875 mg PO q12h, which will cover gram-negative rods, streptococci, and anaerobes, or ciprofloxacin plus metronidazole or clindamycin. Bactrim will cover MRSA and MSSA and some gram-negative rods.

The expert panel on diabetic foot infection (DFI) of the International Working Group on the Diabetic Foot conducted a systematic review. Results of comparisons of different antibiotic regimens generally demonstrated that newly introduced antibiotic regimens appeared to be as effective as conventional therapy.

Chronic Treatment

  • Length of therapy: Highly variable depending on the severity of the infection. In general, 2 to 4 wk of antibiotics is sufficient. If bone infection suspected or documented, may need 4 to 8 wk of antibiotics, preferably intravenous 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 revascularization in the therapy of chronic, nonhealing wounds associated with diabetes. Evidence of effectiveness is conflicting. HBO acts by:
    1. Inducing vasoconstriction and reducing vasogenic edema
    2. Facilitating fibroblast activity, angiogenesis, and wound healing
    3. Killing anaerobic bacteria and augmenting neutrophil bactericidal activity
  • Negative pressure wound therapy (wound vac): Controlled, subatmospheric pressure applied to an open wound can accelerate healing and closure.
    1. An open cell foam insert is cut to fit the open wound and then secured under a clear, vapor-permeable, plastic dressing.
    2. Tubing extends from the sponge to a disposable collection canister.
    3. A portable pump applies 125 mm Hg of controlled suction to the system. The subatmospheric pressure (suction) is equally distributed across the open wound and evacuates stagnant fluid from the wound.
Disposition

  • Following up on sed rates, CRP, BUN/CR, and levels of vancomycin if that antibiotic used.
  • Surgical or wound center care follow-up.
  • 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 two to five times as high as the risk for a patient with diabetes without a foot ulcer.
Referral

  • Infectious disease consultant for antibiotic management
  • Surgeon or wound care center for surgical treatments
  • Endocrinologist for good diabetes care
  • Vascular surgeon for angioplasty or bypass procedures

Pearls & Considerations ⬆ ⬇

Suggested Readings ⬆

    1. Adam A. : Grainger and Allison’s diagnostic radiology, ed 6, Philadelphia, 2015, Elsevier Grant L.A., editors : Grainger & Allison’s diagnostic radiology essentials. ed 2Elsevier-Philadelphia, 2019.
    2. Armstrong D. : Diabetic foot ulcers and their recurrenceN Engl J Med. ;376:2367-2375, 2017.
    3. Frykberg R.G. : A multinational, multicenter, randomized, double-blinded, placebo-controlled trial to evaluate the efficacy of cyclical topical wound oxygen therapy (TWO2) in the treatment of chronic diabetic foot ulcers: the TWO2 studyDiabetes Care. ;43(3):616-624, 2020.
    4. Hart T. : Management of diabetic footJAMA. ;318(14):1387-1388, 2017.
    5. Hobizal K., Wukich D. : Diabetic foot infections: current concept reviewDiabet Foot Ankle. ;3(10), 2012.http://3402/dfa.v3i0.18409.org
    6. Lipsky B.A. : Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infectionsClin Infect Dis. ;54(12):e132-e173, 2012.
    7. Peters E.J. : Interventions in the management of infection in the foot in diabetes: a systematic reviewDiabetes Metab Res Rev. ;32(Suppl 1):145-153, 2016.
    8. Santema K.T.B. : Hyperbaric oxygen therapy in the treatment of ischemic lower-extremity ulcers in patients with diabetes: results of the Damocles multicenter randomized clinical trialDiabetes Care. ;41, 2018.