Diabetic Foot Infection

Diabetic foot ulcer (DFU) is the most frequently recognized complication of diabetes. Patients with foot ulcers have increased mortality, and more than 50% of ulcers become infected. Infected ulcers can progress to larger wounds, gangrene, and osteomyelitis, and lead to amputations and death. Therefore, it is important to recognize and treat diabetic foot infection (DFI) early and appropriately. In this section, we cover the following topics related to DFI:

• Pathophysiology

• Diagnosis

• Treatment

• Prevention

Pathophysiology

Diabetes causes neuropathic and vascular changes that lead to ulcer formation, as shown in the figure below.

Diabetic foot ulcers and their recurrences are caused by a number of factors that ultimately lead to skin breakdown. These factors include sequelae related to sensory, autonomic, and motor neuropathies. (Source: Diabetic Foot Ulcers and Their Recurrence. N Engl J Med 2017.)

Diagnosis

Although there are no clear clinical criteria for diagnosing DFI, typically signs of inflammation (e.g., redness, warmth, swelling, pain), purulence, friable or discolored granulation tissue, undermining of wound edges, and foul odor can point to infection.

Risk factors that increase the likelihood of infection include:

• positive probe-to-bone (PTB) test

• ulcer present for >30 days

• recurrent foot ulcers

• traumatic foot wound

• peripheral arterial disease

• lower-extremity amputation

• loss of protective sensation

• renal insufficiency

• walking barefoot

Acute DFIs are classified into three categories:

• mild: superficial and limited in size and depth; can be treated with oral antibiotics on an outpatient basis

• moderate: deeper or more extensive; may require initial broad-spectrum parenteral agents before transitioning to oral outpatient therapy; hospitalization depends on complicating factors (e.g., peripheral artery disease, poor social support)

• severe: accompanied by systemic signs or metabolic derangements; requires hospitalization and initial broad-spectrum parenteral agents

Evaluation: Examine the wound and both feet to inspect for ulcers on the contralateral side and assess pulses or blood flow to the extremities. Probe the infected area with a swab to evaluate depth and extension below the skin surface, especially if the probe reaches bone (positive PTB test). A positive PTB test has a high positive predictive value for concurrent osteomyelitis in patients with ulcers highly suspicious of infection.

Diagnostic tests to consider:

• complete blood count, C-reactive protein, and erythrocyte sedimentation rate

• blood cultures: generally low-yield even in the setting of osteomyelitis

• wound cultures: collect before receipt of antibiotics if possible and from deep tissue; avoid superficial swabs (prone to detecting the colonizing organisms) unless purulent exudate is cultured

• vascular studies: a low ankle-brachial index (ABI) can indicate peripheral vascular disease, which may require intervention to improve blood flow for healing

• radiography: plain radiograph can identify bony abnormalities (e.g., from chronic osteomyelitis), soft-tissue gas, or foreign bodies

• magnetic resonance imaging (MRI): the imaging modality of choice for early acute osteomyelitis; three-phase technetium bone scan and labeled leukocyte scan are alternatives if MRI is contraindicated

• bone biopsy: gold standard for diagnosing osteomyelitis; directs antibiotics choice

Treatment

A multidisciplinary team, often involving wound care specialists, podiatrists, primary care physicians or diabetic specialists, and surgeons can improve long-term outcomes and prevent recurrences of DFI.

Proper treatment of DFI requires the following:

• adherence to antibiotic regimen

• good glycemic control

• off-loading of the foot

• aggressive wound care

• close monitoring of wound healing

Antibiotics: Most infections are polymicrobial with aerobic gram-positive cocci, aerobic gram-negative bacilli, and anaerobes. Empiric treatment selection depends on severity of illness and suspicion for methicillin-resistant Staphylococcus aureus (MRSA) infection (risks include high local prevalence) or Pseudomonas (risks include high local prevalence of Pseudomonas infection, warm climate, frequent foot exposure to water).

The following table of empiric antibiotic regimens suggested in the 2012 Infectious Diseases Society of America (IDSA) guideline can be helpful in decision-making when choosing an agent for treatment. Treatment duration varies (1-3 weeks, depending on severity) and should continue until resolution of findings of infection but not necessarily until healing of ulcer. Antimicrobial susceptibility should be reassessed based on local microbiogram data.

Surgical intervention may be required in addition to empiric intravenous antibiotics in patients with moderate-to-severe infections to remove necrotic tissue, including infected bone; release compartment pressure; or drain abscesses.

Urgent revascularization may be considered in patients with peripheral artery disease.

Treatment of Osteomyelitis

Treatment of osteomyelitis requires antibiotics that can achieve therapeutic levels in bone tissue. Intravenous antibiotics are not always needed because some oral options have excellent bioavailability. Treatment duration is typically ≥6 weeks but can be shorter if amputation or debridement removed all infected tissue. It’s important to ensure that a patient completes the full course for osteomyelitis because an ulcer will not heal if the underlying bone is still infected.

Revascularization: In cases of vascular ischemia, a surgeon (general or vascular, depending on vascular state of the limb) should be consulted urgently. Most diabetic foot infections will require wound debridement in the operating room or at the bedside.

Prevention

Ulcer recurrence is ~40% within 1 year and ~65% within 5 years. Because many risk factors do not disappear after ulcers heal, it is useful to think of ulcers as being in remission rather than cured. Patients are vulnerable to new ulcers shortly after an existing ulcer heals because the skin is still weak. A false sense that the ulcer problem is gone leads to poor adherence to preventative therapies and is one of the biggest treatment challenges.