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Infectious Diseases - Diabetic Foot Infection - Fast Facts | NEJM Resident 360

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.

Figure 1. Common Pathway of Diabetic Foot Ulcer Occurrence and Recurrence. 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

Examine the wound and both feet to examine 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). 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

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

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.

Acute DFIs are classified into three categories:

1. mild: superficial and limited in size and depth; can be treated with oral antibiotics on an outpatient basis
2. moderate: deeper or more extensive; may require initial broad-spectrum parental agents before transitioning to oral outpatient therapy; hospitalization depends on complicating factors (e.g., peripheral artery disease, poor social support)
3. severe: accompanied by systemic signs or metabolic derangements; requires hospitalization and initial broad-spectrum parental agents

In addition to empiric parenteral intravenous antibiotics, surgical intervention may be required 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.

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 help guide 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.

 Suggested Empiric Antibiotic Regimens Based on Clinical Severity for Diabetic Foot Infections

Severity	MRSA	Pseudomonas	Anaerobes	Antibiotic	Notes
Mild	No	No	No	Dicloxacillin (PO)
Cephalexin (PO)	Focused on gram-positive
organisms
Yes	No	No	Doxycycline (PO)
Trimethoprim–sulfamethoxazole (PO)	May not have adequate
strep activity alone
No	No	Yes	Amoxicillin–clavulanate (PO)
Yes	No	Yes	Clindamycin (PO/IV)	May not have reliable MRSA activity
Moderate or Severe	No	No	No	Ceftriaxone (IV/IM)
Moxifloxacin (PO/IV)	Add metronidazole (PO/IV) for anaerobic activity
No	No	Yes	Cefoxitin (IV)
Ampicillin–sulbactam (IV)
Ertapenem (IV/IM)
No	Yes	No	Ciprofloxacin (PO/IV)
Levofloxacin (PO/IV)
Ceftazidime (IV)
Cefepime (IV)
Aztreonam (IV)	Add metronidazole (PO/IV) for anaerobic activity
Yes	No	No	Linezolid (PO/IV)
Vancomycin (IV)
Daptomycin (IV)	Toxicity with >2 weeks use
No	Yes	Yes	Piperacillin–tazobactam (IV)
Imipenem–cilastatin (IV)
Meropenem (IV)

Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; PO, by mouth; IV, intravenously; IM, intramuscularly;

(Adapted from: 2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections. Clin Infect Dis 2012.)

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 ≥4 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.

Prevention of Ulcers and Treatment of Noninfected Ulcers

Prevention of Ulcers	Treatment of Noninfected Ulcers

• patient education

• home self-check for ulcers

• early detection of preulcerous lesions (e.g.,
  hemorrhagic callus, plantar inflammation
  as detected by elevated foot
  temperatures)

• prescription therapeutic footwear

• foot surgery in patients with ulcers that
  are nonresponsive to nonsurgical treatments

• improved glycemic control

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• off-loading with crutches, wheelchairs, shoe modifications

• debridement of any necrotic tissue at risk for infection

• irrigation with sterile saline or water with dressing changes

• adjunctive therapy (none proven to be clearly effective) if healing is slow:

• • hyperbaric oxygen therapy

  • growth factors

  • platelet-rich plasma

  • negative pressure wound therapy

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