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Oct.09.2019

Diabetic foot infection

Synopsis

Key Points

  • Diabetic foot infection is an infection, often originating from an ulcer, that occurs in a patient with diabetes mellitus
    • Clinically important because it heals slowly, can progress, and is associated with high morbidity and serious complications (eg, osteomyelitis, gangrene, amputation)
  • Clinical presentation varies widely, depending on extent and duration of infection and patient's degree of sensory impairment
    • Local features include purulence, erythema, induration, tenderness, or calor
    • May be accompanied by systemic indicators of infection such as fever or hypothermia, tachycardia, or tachypnea
  • Diagnosis is clinical, based on presence of local and systemic signs and symptoms of inflammation
    • Plain radiographs are indicated in all patients; perform MRI if abscess or osteomyelitis is suspected
    • Obtain a CBC, serum chemistries, and sedimentation rate or C-reactive protein level in all patients whose clinical examination suggests infection; consider measuring procalcitonin
    • Obtain deep cultures after thorough cleansing and preliminary debridement
    • Assess vascular status in all patients, beginning with ankle-brachial index
  • Infection may be classified as follows according to Infectious Diseases Society of America and International Working Group on the Diabetic Foot:
    • Uninfected (grade 1): no symptoms or signs of infection
    • Mild (grade 2): infection is confined to skin and subcutaneous tissue; erythema, if present, extends no further than 2 cm around the ulcer
    • Moderate (grade 3): infection extends beneath subcutaneous tissue, or erythema exceeds a 2-cm rim around the ulcer
    • Severe (grade 4): local infection is associated with 2 or more signs of systemic infection
  • Treatment includes antibiotic therapy and wound care
    • Antibiotic therapy is recommended for all patients; selection of empiric regimens is based on severity of infection and risk factors for MRSA and Pseudomonas aeruginosa
    • Aggressive wound care is essential, beginning with surgical debridement
    • Offloading of pressure is critical to healing, but it must allow frequent wound inspection and dressing changes until infection clears
  • Prognosis is guarded; about 20% of moderate to severe infections require amputation; in the remainder, healing is often very slow and/or incomplete
  • Prevention focuses on avoiding injury and ulceration through education, structural deformity correction, and vulnerable surface protection through use of orthotics and prescription shoes; good glycemic control and regular follow-up are also essential

Urgent Action

  • Severe diabetic foot infection carries significant risk of limb loss and may be life-threatening
    • These patients require urgent hospitalization, antibiotics, and surgical evaluation

Pitfalls

  • Patients at highest risk for infection lack the ability to perceive it because they often have sensory neuropathy and retinopathy; family members or other caretakers must be vigilant on patient's behalf for signs of foot injury and infection
  • Infection often leads to hyperglycemia and may precipitate diabetic ketoacidosis or other metabolic derangements

Terminology

Clinical Clarification

  • Diabetic foot infection is an infection, often originating from an ulcer, that occurs in a patient with diabetes mellitus
    • Clinically important because it heals slowly, can progress, and is associated with high morbidity and serious complications (eg, osteomyelitis, gangrene, amputation)
  • Spectrum of disease varies from superficial local cellulitis to chronic osteomyelitis
    • Osteomyelitis is present in about 20% of diabetic foot infections r1

Classification

  • Many diabetic foot ulcer classifications exist; 2 similar and clinically applicable tools that focus on details of infection were created by the Infectious Diseases Society of America and the International Working Group on the Diabetic Foot r2r3
    • Scores for both scales are based on signs, symptoms, and extent of local infection, and on presence or absence of signs of systemic infection
      • Local infection is defined as presence of 2 or more of the following at the infection site:
        • Swelling or induration
        • Erythema
        • Tenderness or pain
        • Increased warmth
        • Purulence
      • Systemic infection signs include the following:
        • Fever (temperature higher than 38°C) or hypothermia (temperature lower than 36°C)
        • Heart rate higher than 90 beats per minute
        • Respiratory rate higher than 20 breaths per minute or PaCO₂ lower than 32 mm Hg
        • WBC count higher than 12,000/mm³ or lower than 4000/mm³ or left shift with 10% or more immature cells
    • Infectious Diseases Society of America classifications range from uninfected to severe infection; corresponding International Working Group on the Diabetic Foot grades are 1 through 4
      • Uninfected (grade 1): no symptoms or signs of infection
      • Mild (grade 2): infection is confined to skin and subcutaneous tissue; erythema, if present, extends no further than 2 cm around the ulcer
      • Moderate (grade 3): infection extends beneath subcutaneous tissue, or erythema exceeds a 2-cm rim around the ulcer
      • Severe (grade 4): local infection is associated with 2 or more signs of systemic infection

Diagnosis

Clinical Presentation

History

  • Clinical presentation varies, depending on extent and duration of infection and patient's degree of sensory impairment
  • Pain may be a presenting symptom in patients who can perceive it
    • Patients with advanced diabetic neuropathy may not experience pain, even in presence of severe infection; those with impaired vision (eg, severe retinopathy) may not be able to see signs of infection to report them
  • Fever or chills may occur, as may other systemic symptoms such as nausea or vomiting
  • As blood glucose becomes more difficult to control in the presence of infection, some symptoms may relate to hyperglycemia, including the following:
    • Blurred vision
    • Polyuria
  • In addition to presenting complaints, other important patient history information includes the following:
    • Previous foot ulcers and outcomes
    • Amputations
    • Vascular surgery or angioplasty
    • Vascular symptoms (eg, claudication, rest pain)
    • Symptoms of neuropathy (eg, paresthesias, numbness)
    • Other indicators of advanced diabetes (eg, renal insufficiency, diabetic retinopathy)
    • Smoking habits (past and present)

Physical examination

  • Assess patient's general appearance; those with severe infection may be pale or flushed, restless, or confused
  • Vital signs may be abnormal; fever is common. Patients with severe infection may be febrile or hypothermic, tachycardic, tachypneic, and/or hypotensive
  • Foot examination
    • Assess for infection, defined by presence of 2 or more of the following:
      • Purulence
      • Erythema
      • Induration
      • Tenderness
      • Increased temperature in overlying or surrounding skin
    • Additional assessment includes
      • Appearance of wound and exposed tissue
        • Paleness may indicate significant ischemia; blood- or beefy-red tissue may indicate better perfusion
        • Presence of eschar or necrotic material
        • Visible or palpable bone at base
          • Gently insert a blunt metal probe to determine whether the base of the wound is soft tissue or bone
          • Exposed bone is associated with osteomyelitis r3
        • Size of the ulcer
          • Larger than 2 cm² increases likelihood of osteomyelitis r3
      • Fluctuance or crepitus on palpation
      • Sensation (eg, pinprick or monofilament, vibratory, proprioceptive)
      • Structural changes contributing to ulceration and infection (eg, Charcot arthropathy, bunion, hammer toe)
      • Edema, which may impede perfusion
      • Skin changes associated with chronic ischemia (eg, shiny appearance, lack of hair)
      • Pulses (ie, dorsalis pedis, posterior tibial)
        • May be diminished; handheld Doppler may aid in identifying flow

Causes and Risk Factors

Causes

  • Most commonly caused by infection of a preexisting diabetic foot ulcer
    • Foot ulcers are common in patients with diabetes and result from a complex interplay of neuropathy and ischemia that causes structural changes and resulting in weight bearing shifts, callus formation, and friction
  • Other breaks in skin integrity, including traumatic wounds and tinea pedis, also may serve as sources of infection
  • Impaired immune function and hyperglycemia foster infection in ulcers and other wounds and skin lesions predisposed to infection
  • Most infections are polymicrobial r3
    • Staphylococci (including MRSA) and streptococci are most common
    • Aerobic gram-negative bacilli (eg, Escherichia coli) are frequently involved, especially in patients who have received previous antibiotics
    • Anaerobes may play a role in ischemic or necrotic tissue

Risk factors and/or associations

Other risk factors/associations
  • Peripheral artery disease due to atherosclerosis is present in up to 50% of patients with a diabetic foot ulcer r2
  • The following wound characteristics are associated with a higher risk for infection: r4
    • Neuropathic or traumatic wound
    • Exposed bone
    • Prolonged (more than 30 days) or recurrent wound
    • Associated with peripheral arterial disease
  • Risk factors for foot ulcers, a common precursor to diabetic foot infection, include the following: r5
    • Foot deformity
    • Peripheral neuropathy
    • Peripheral vascular disease
    • Poor glycemic control
    • Diabetic nephropathy
    • Visual impairment
    • Previous foot ulcer
    • Previous amputation
    • Cigarette smoking

Diagnostic Procedures

Primary diagnostic tools

  • Clinical diagnosis is based on presence of local signs and symptoms of inflammation, with or without systemic signs r6
  • Evaluation begins with a thorough history and physical examination
  • Assess wound characteristics, if present:
    • Define extent (size) and depth of wound after cleaning and debridement
      • Probe-to-bone test for open wounds r6
        • Gently insert blunt sterile metal probe through wound to determine if wound is through to bone (detected by hard, gritty feel)
        • This test can help diagnose (when likelihood is high) or exclude (when likelihood is low) osteomyelitis
  • Obtain specimens of infected wounds for culture after cleaning and debridement r3r6
    • Do not culture clinically uninfected wounds
    • In patients with suspected osteomyelitis, arrange for bone biopsy to obtain culture and histopathology
  • Obtain CBC, serum chemistries, and sedimentation rate or C-reactive protein in all patients whose clinical examination suggests infection; consider measuring procalcitonin level r3r7
  • Assess severity of infection using classification scheme from the Infectious Diseases Society of America/International Working Group on the Diabetic Foot r6
    • Based on extent and depth of infection and presence of systemic signs of infection
    • Can guide choice of empiric antibiotic regimen, route of administration, and help determine need for hospitalization
  • Obtain ankle-brachial index or toe-brachial index to assess vascular supply, particularly in patients with nonpalpable or weak distal pulses r3r6
    • Further evaluation of vascular supply (eg, angiography) may be indicated in some patients, but usually not acutely
  • Imaging is indicated if there is a question of a deep abscess or osteomyelitis
    • Plain radiographs are recommended for all patients as the initial study, but the radiographs may be negative early in the infection course r3r6r8
    • MRI is the most sensitive study for detecting osteomyelitis, especially early in the infection course, and can detect soft tissue abscess r3r6
    • If MRI cannot be done, a radionuclide-labeled WBC scan is recommended when osteomyelitis is suspected r3r6

Laboratory

  • CBC
    • Elevated WBC count supports the diagnosis of infection, but a normal value does not exclude it
      • Criteria for severe infection include the following: r3
        • WBC levels below 4000 cells/mm³
        • WBC levels above 12,000 cells/mm³
        • Left shift with 10% or more immature cells
  • Serum chemistry studies
    • Infection may be associated with hyperglycemia; correction of hyperglycemia is associated with lower complication rates in hospitalized patients r9
    • Renal insufficiency may limit antibiotic choices or necessitate dose adjustments
  • Erythrocyte sedimentation rate
    • Elevated rate is associated with infection; can use serial measurements to assess response to treatment
    • Level higher than 60 mm/hour suggests underlying osteomyelitis, especially in conjunction with an ulcer depth of 3 mm or more and a C-reactive protein of 3.2 mg/dL or higher r10
  • C-reactive protein
    • Elevated level is associated with infection; can use serial measurements to assess response to treatment
    • Level higher than 3.2 mg/dL suggests associated osteomyelitis, especially in conjunction with an ulcer depth of 3 mm or more and a sedimentation rate of 60 mm/hour or higher r10
  • Procalcitonin
    • Elevated procalcitonin, especially in conjunction with an elevated C-reactive protein, can help discriminate infection from other conditions (eg, noninfected ulcer) r3
  • Cultures r3
    • Deep cultures of soft tissue, obtained by biopsy or curettage after debridement and lavage, may identify most accurately the infecting organism(s)

Imaging r11

  • Plain radiographs
    • Useful in further defining bony deformities (Charcot foot), and may reveal osteomyelitis (periosteal elevation, cortical erosion) or even a foreign body
    • Presence of radiolucent gas bubbles in soft tissue can indicate severe infection (eg, gas gangrene, necrotizing fasciitis) r1
    • In patients whose imaging studies are negative initially, serial radiographs during course of treatment are recommended to enable early detection of developing osteomyelitis r8
  • MRI
    • Most sensitive and specific imaging test for diagnosing osteomyelitis and for defining extent of disease
    • Normal marrow signal essentially excludes diagnosis of osteomyelitis
  • Radionuclide-labeled WBC scan
    • May be done in conjunction with 3-phase bone scan
    • Indicated when osteomyelitis is suspected and MRI cannot be performed; also helpful in discriminating infection from other abnormalities associated with orthopedic hardware, previous surgery, or trauma
    • In the presence of neuropathic arthropathy, scans may be positive or indeterminant, but a negative scan excludes the diagnosis of osteomyelitis

Procedures

Bone biopsy r3
General explanation
  • Sampling of bone for histopathologic examination and microbiologic culture
  • Specimens may be obtained via surgical or needle biopsy, or they may be obtained during debridement
    • In stable patients, in whom there is minimal soft tissue infection, ideally obtain specimens before initiating antibiotics
    • In patients with significant soft tissue infection, do not delay antimicrobial therapy
  • Perform both aerobic and anaerobic cultures on biopsy specimens
Indication
  • Use in patients with suspected osteomyelitis associated with diabetic foot infection to make a definitive diagnosis and identify causative pathogen
Interpretation of results
  • Gold standard for diagnosis of osteomyelitis is positive culture result from bone biopsy accompanied by histopathologic signs of necrosis
  • Histopathologic analysis demonstrates necrotic bone and inflammatory exudate
  • Culture results identify causative pathogens and reveal antimicrobial susceptibility pattern

Other diagnostic tools

  • Ankle-brachial index to assess vascular perfusion r3
    • Recommended for all patients with diabetic foot infection, especially if pulses are diminished or absent
    • Accuracy in predicting peripheral artery disease is variable, especially in presence of neuropathy or arterial calcification, but the test is noninvasive, easy to do, and requires no special equipment r12
      • Place blood pressure cuff above ankle and measure systolic blood pressure in dorsalis pedis and/or posterior tibial artery, with aid of a handheld Doppler, if necessary r5
      • Divide result by brachial systolic value to calculate the ankle-brachial index r3r5
        • Reference range is 0.91 to 1.3
        • 0.6 to 0.89 indicates mild perfusion deficit and may be associated with claudication
        • 0.4 to 0.59 indicates moderate obstruction to perfusion
        • Less than 0.4 indicates severely reduced flow and may be associated with rest pain
        • More than 1.3 indicates arterial calcification and is an unreliable indicator of perfusion
  • Toe pressure r13
    • Requires toe pressure cuff and handheld Doppler
    • Wrap toe cuff around great toe and measure systolic pressure using Doppler placed distal and medial to the cuff
    • Pressure lower than 30 mm Hg indicates significantly impaired perfusion
  • Skin perfusion pressure and transcutaneous oxygen pressure
    • Require special equipment, but help assess prognosis

Differential Diagnosis

Most common

  • Acute Charcot arthropathy
    • Deforming arthropathy (foot or ankle collapse) resulting from neuropathy, repetitive minor trauma, and bone remodeling
    • Like diabetic foot infection, may present as unilateral swelling of the foot with erythema and calor
    • Symptoms, signs, and laboratory evidence of infection are absent
    • Imaging (eg, MRI scan) may be necessary to definitively differentiate from diabetic foot infection, especially if there is a break in skin integrity that might have served as a portal for infection
  • Gout d1
    • Crystalline arthropathy caused by deposition of monosodium urate crystals
    • May present as a hot swollen joint (eg, first metatarsophalangeal joint, ankle) and may be associated with tenosynovitis; extremely painful in patients who have normal sensation
    • May be clinically indistinguishable from diabetic foot infection, although the latter usually has an identifying portal for infection
    • Elevated serum uric acid suggests the diagnosis, which can be confirmed by aspirating synovial fluid and demonstrating negatively birefringent crystals
  • Fracture
    • Fracture after unrecognized trauma may occur in patients with diabetes who have severe sensory impairment in their feet
    • Patient may present with swollen, erythematous foot, with or without pain or detectable tenderness
    • Differentiated by imaging; plain radiographs may or may not demonstrate fracture early on, and MRI may be necessary

Treatment

Goals

  • Eradicate infection, heal underlying wound if present, and prevent complications such as osteomyelitis or amputation

Disposition

Admission criteria

Infectious Diseases Society of America recommends admission based on a combination of severity classification and individual patient circumstances such as significant comorbidities or inadequate outpatient support

  • Admit all patients who have severe infection
    • Characterized by evidence of local infection (eg, erythema, purulence) plus any of the following systemic indicators of infection: r3
      • Fever or hypothermia
      • Heart rate higher than 90 beats per minute
      • More than 20 breaths per minute or PaCO₂ lower than 32 mm Hg
      • Peripheral WBC count higher than 12,000 cells/mm³ or lower than 4000 cells/mm³
      • Left shift with 10% or more immature forms
  • Also admit patients who have mild or moderate infection and any of the following issues:
    • Unable to care for themselves
    • Inadequate help to care for themselves
    • Have not improved despite outpatient management
Criteria for ICU admission
  • Patients with severe infection (eg, gangrene, necrotizing infection) and hemodynamic instability or associated severe metabolic derangements (eg, diabetic ketoacidosis)

Recommendations for specialist referral

  • Specialist teams, where available, are recommended r3r7r14
  • Consult an infectious disease specialist to select empiric antibiotics, interpret culture results, and refine care regimen
  • Consult a surgeon with debridement expertise to debride open wounds; this may be a general or orthopedic surgeon or a podiatric surgeon with advanced training
  • Consult a vascular surgeon if there is evidence of ischemia to evaluate and determine whether revascularization is needed to improve management of infection and increase chance of healing
  • Consult a plastic or reconstructive surgeon if tissue replacement or wound coverage is required
  • Consult an endocrinologist to optimize control of blood glucose levels
  • Consult an orthopedist or podiatrist for proper protective and offloading device to avoid pressure or friction on the affected area

Treatment Options

Cleanse and debride wounds or ulcers r3

  • Debridement is usually done surgically, but in some cases mechanical (eg, wet-to-dry dressings), autolytic, or combination debridement is appropriate
    • Serial debridement may be necessary
  • Drain deep collections; decompress compartments under pressure

Give all patients with infection empiric antibiotics. No single regimen has proven superior;r15 selection of antibiotics is determined by severity of infection and likely infecting pathogens r3

  • Oral antibiotics are appropriate for most mild and some moderate infections; severe infections initially require parenteral agents
  • For mild to moderate infections in patients who have not recently received antibiotics (for this or other infections), use a regimen aimed at staphylococci and aerobic streptococci
    • For patients who have received antibiotics recently, use additional coverage for gram-negative bacilli
  • For severe infections, use broad spectrum therapy against both aerobic and anaerobic organisms
  • Empiric coverage of MRSA is recommended in the following circumstances:
    • Patients who have been infected or colonized with MRSA within the past year
    • Areas where local rate of methicillin resistance among Staphylococcus aureus isolates exceeds 30% (for moderate infection) to 50% (for mild infection)
    • Severe infections, in which delayed coverage while awaiting cultures is thought to pose an unacceptable risk to the patient
  • Consider coverage of Pseudomonas aeruginosa in patients with severe infection and in circumstances that foster its role as a pathogen (eg, warm, moist climate; frequent use of foot soaks)

Infectious Diseases Society of America offers the following recommended regimens for empiric treatment: r3

  • For mild infection in which MRSA is unlikely to play a role, any of the following agents are recommended as single-drug therapy:
    • Dicloxacillin
    • Clindamycin
    • Cephalexin
    • Levofloxacin
    • Amoxicillin-clavulanate
  • For mild infection with risk factors for MRSA:
    • Doxycycline
    • Trimethoprim-sulfamethoxazole
  • For moderate or severe infections without risk factors for MRSA or Pseudomonas aeruginosa:
    • Levofloxacin
    • Cefoxitin
    • Ceftriaxone
    • Ampicillin-sulbactam
    • Moxifloxacin
    • Ertapenem
    • Tigecycline
    • Levofloxacin or ciprofloxacin with clindamycin
    • Imipenem-cilastatin
  • For moderate or severe infections with MRSA risk, add 1 of the following:
    • Linezolid
    • Daptomycin
    • Vancomycin
  • For moderate to severe infections with risk for Pseudomonas aeruginosa:
    • Piperacillin-tazobactam

When culture results are available, modify antibiotic regimen accordingly, if indicated

Duration of antibiotic treatment

  • 1 to 3 weeks of antibiotics is sufficient for most soft tissue infections, and a parenteral regimen may be switched to an oral regimen once the patient has improved r3
  • For osteomyelitis in which bone has been adequately debrided, usual treatment course is at least 4 weeks r3
    • If the infected bone has been completely resected, aim therapy at treating any residual soft tissue infection
    • For patients with residual necrotic bone (ie, not adequately debrided), may continue antibiotics for 3 months or longer

Use of granulocyte colony–stimulating factor in patients with infected wounds has not been shown to have a significant impact on resolution of infection or wound healing, but it may reduce duration of hospital stay and need for amputation r16

  • Guidelines do not recommend routine use r3r6r14

Meticulous wound care is an essential part of treatment, and involves the following:

  • Dressings to protect the wound and maintain a moist environment
  • Offloading of pressure from the wound, particularly when the plantar surface is involved

Early revascularization may be required to restore adequate blood supply for treatment of infection (delivery of antibiotics and host defenses) r3r7

Optimize glycemic control r7d2

  • Hyperglycemia in hospitalized patients is defined as blood glucose levels more than 140 mg/dL r17
  • Once insulin therapy is started, a target glucose range of 140 to 180 mg/dL is recommended for most critically ill patients and noncritically ill patients r17

Drug therapy

  • Penicillins
    • Dicloxacillin
      • Dicloxacillin Sodium Oral capsule; Adults, Adolescents, and Children weighing >= 40 kg: 125 to 250 mg PO q6h for mild/moderate infections; 250 to 500 mg PO q6h for severe infections. Max 4 g/day PO.
    • Amoxicillin-clavulanate
      • Amoxicillin Trihydrate, Clavulanate Potassium Oral tablet; Adults, Adolescents, and Children weighing 40 kg or more (every 8 hour regimens): 250 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours (using 250 mg tablet) for mild/moderate infections and 500 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours (using 500 mg regular tablets; 125 mg or 250 mg chewable tablets; or 125 mg/5 mL or 250 mg/5 mL suspension) for severe infections.
    • Ampicillin-sulbactam
      • Ampicillin Sodium, Sulbactam Sodium Solution for injection; Adults: 1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV/IM every 6 hours. Duration depends on severity; typically 1 to 4 weeks.
    • Piperacillin-tazobactam
      • Piperacillin Sodium, Tazobactam Sodium Solution for injection; Adults: 3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours for 7 to 10 days.
  • Cephalosporins
    • Cephalexin
      • Cephalexin Monohydrate Oral capsule; Adults: 1 to 4 g daily, divided in 2 to 4 equal doses and generally 250 mg PO every 6 hours or 500 mg PO every 12 hours; higher doses for severe infections. Max: 4 g/day. Generally treat 7 to 14 days. Guidelines recommend 500 mg PO every 6 hours for methicillin-susceptible Staphylococcal aureus (MSSA) or streptococcal infections and 250 mg PO every 6 hours for 7 days impetigo or ecthyma.
    • Cefoxitin
      • Cefoxitin Sodium Solution for injection; Adults: 1 g IV/IM every 6 to 8 hours for uncomplicated infections, and 1 g IV every 4 hours or 2 g IV every 6 to 8 hours for moderately-severe or severe infections. For infections requiring higher doses, 2 g IV every 4 hours or 3 g IV every 6 hours can be used. Max: 12 g/day.
    • Ceftriaxone
      • Ceftriaxone Sodium Solution for injection; Adults: 1 to 2 g IV/IM every 12 to 24 hours (Max: 4 g/day) depending on severity of illness and causative organism for 1 to 2 weeks for moderate or severe diabetic wound infections.
  • Carbapenems
    • Ertapenem
      • Ertapenem Solution for injection; Adults: 1 g IV/IM once daily for 7 to 14 days. For mixed necrotizing skin infections, surgical intervention is primary therapeutic intervention. Treat until further debridement not necessary, patient improved clinically, and fever absent for 48 to 72 hours. Depending on severity of illness and causative organism, treat for 1 to 2 weeks for moderate or severe diabetic wound infections. For cat or dog bite, preemptive therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of bite area, have moderate to severe injuries, or have penetrating injuries to periosteum or joint capsule.
    • Imipenem-cilastatin
      • Imipenem, Cilastatin Sodium Solution for injection; Adults: 500 mg IV every 6 hours or 1 g IV every 8 hours for fully susceptible organisms and 1 g IV every 6 hours for organisms with intermediate susceptibility.
  • Fluoroquinolones
    • Levofloxacin
      • Levofloxacin Oral tablet; Adults: 500 mg PO every 24 hours for 7 to 10 days for uncomplicated infections; 750 mg PO every 24 hours for 7 to 14 days for complicated infections. Clinical guidelines suggest treating for 1 to 2 weeks for mild/moderate diabetic foot infections.Levofloxacin Oral tablet; Adults: 500 mg PO every 24 hours for 7 to 10 days for uncomplicated infections; 750 mg PO every 24 hours for 7 to 14 days for complicated infections. Clinical guidelines suggest treating for 1 to 2 weeks for mild/moderate diabetic foot infections.
    • Moxifloxacin
      • Moxifloxacin Hydrochloride Oral tablet; Adults >= 18 years: 400 mg PO or IV q24 hours for 7—21 days.
  • Sulfonamide
    • Trimethoprim-sulfamethoxazole
      • Sulfamethoxazole, Trimethoprim Oral tablet; Adults: 160 to 320 mg trimethoprim/800 to 1,600 mg sulfamethoxazole PO every 12 hours for 5 to 10 days.Sulfamethoxazole, Trimethoprim Oral tablet; Adults: 160 to 320 mg trimethoprim/800 to 1,600 mg sulfamethoxazole PO every 12 hours for 5 to 10 days.
  • Lincosamide
    • Clindamycin
      • Clindamycin Solution for injection; Adults: 300 mg IV/IM every 6 to 12 hours for less severe infections and 600 mg IV/IM every 6 to 12 hours to 900 mg IV every 8 to 12 hours for more severe infections. Guidelines suggest clindamycin monotherapy for mild infections or combination therapy with ciprofloxacin or levofloxacin for moderate to severe diabetic wound infections. Treat for 1 to 2 weeks.
  • Tetracycline
    • Doxycycline
      • Doxycycline Hyclate Oral capsule; Adults, Adolescents, and Children 8 years and older and weighing 45 kg or more: 100 mg PO every 12 hours for 5 to 10 days for CA-MRSA plus a beta-lactam if beta-hemolytic streptococci coverage is necessary.
  • Glycylcycline
    • Tigecycline
      • Tigecycline Solution for injection; Adults: 100 mg IV initially, then 50 mg IV every 12 hours over 30 to 60 minutes; give for 5 to 14 days guided by the severity and site of infection and patient's clinical and bacteriological progress.
    • National Institute for Health and Care Excellence guidelines recommend against tigecycline unless no suitable alternatives exist r14
    • Found in a systematic review to cause more side effects than an alternate regimen of the same antimicrobial spectrum r15
  • Glycopeptide
    • Vancomycin
      • Vancomycin Hydrochloride Solution for injection; Adults: 2 g/day IV divided as 500 mg every 6 hours or 1 g every 12 hours. ASHP, IDSA, and SIDP suggest 15 to 20 mg/kg (actual body weight) IV every 8 to 12 hours; for seriously-ill patients, use a loading dose of 25 to 30 mg/kg (actual body weight) IV. Treat for 7 to 14 days for complicated skin and skin structure infections due to MRSA.
  • Oxazolidinone
    • Linezolid
      • Linezolid Oral tablet; Adults: 600 mg PO every 12 hours for 10 to 14 days. NOTE: Not studied for decubital ulcers. IDSA recommends 600 mg PO every 12 hours for 7 to 14 days as option for MRSA.
  • Lipopeptide
    • Daptomycin
      • Daptomycin Solution for injection; Adults: 4 mg/kg/dose IV every 24 hours for 7 to 14 days.
    • A systematic review of antibiotics for diabetic foot infection found fewer adverse effects than with vancomycin r15

Nondrug and supportive care

Wound care

  • Numerous studiesr18 have sought to identify the optimal dressing, although most studies have been done on patients with noninfected diabetic foot ulcers; in that setting, no superior dressing has been identified. Infectious Diseases Society of America makes the following general recommendations:r3
    • For dry or necrotic wounds, apply frequently moistened saline gauze or hydrogel dressings; the latter aids autolytic debridement
    • Occlusive or semi-occlusive dressings retain moisture in dry wounds
    • Alginates, foams, and hydrocolloid reduce or absorb exudate; the latter also facilitates autolytic debridement
    • Topical antimicrobial dressings (eg, silver-based) are not recommended
  • Offloading (ie, preventing pressure on affected area), allows progressive healing, but it must be balanced with need for frequent dressing changes and wound inspections r3
    • Total contact cast is gold standard for noninfected foot ulcers, but removable devices are better while treating infection
  • Other diabetic foot infection treatments that have not shown clear benefit and that are not currently routinely recommended include hyperbaric oxygen, platelet-derived growth factors, negative pressure wound therapy with or without instillation, and bioengineered skin equivalents r3r6r14
    • Some of these treatments have been shown to help heal diabetic foot ulcers and may help heal refractory ulcers once infection is resolved
Procedures
Debridement
General explanation
  • Removal of infected, devitalized, and necrotic tissue. Usually done surgically (ie, sharp debridement), but auxiliary methods include mechanical (eg, wet-to-dry dressings) or chemical (eg, dressings that promote autolysis)
Indication
  • Presence of infected or necrotic tissue
Interpretation of results
  • Debridement is adequate when wound bed is clean and remaining tissue is red and bleeds easily

Comorbidities

  • Patients with coexisting atherosclerosis may require revascularization to heal or to optimize level of amputation r3
  • Many patients with diabetes also have ischemic heart disease, which may increase risk for surgical procedures r7

Monitoring

  • Inspect infected wounds frequently, daily while in hospital
    • Document wound size, extent of surrounding erythema, amount and character of drainage or exudate, and quality of exposed tissue. Periodic photographs are helpful

Complications and Prognosis

Complications

  • Severe infection may result in sepsis and death d3
  • Infection that cannot be controlled may necessitate amputation
  • Extensive infection may result in significant tissue loss and gait disturbance, exacerbating risk for further ulceration and infection
  • Infection may precipitate uncontrolled hyperglycemia, including diabetic ketoacidosis d4

Prognosis

  • Both short- and long-term prognosis is guarded
    • About 20% of moderate to severe infections require amputation at some level r19
    • At 1-year follow-up of patients hospitalized for diabetic foot infection in 1 series, only 30% of patients had experienced resolution of infection and complete wound healing r3r20
      • 35% of patients required an amputation during the initial hospitalization; over the following year, another 19% required amputation
      • 21% had persistent or recurrent infection
    • Overall mortality 5 years after an amputation for diabetic foot infection is 70% r19
  • In an individual patient, favorable prognostic markers include the following: r13
    • Toe pressure 30 mm Hg or higher
    • Skin perfusion pressure 40 mm Hg or higher
    • Transcutaneous oxygen pressure 25 mm Hg or higher
  • Average time to healing for a noninfected diabetic foot ulcer is 20 weeks r3

Screening and Prevention

Prevention

  • Foot ulcers are a common precursor to infection, and all patients with diabetes should have their feet examined regularly to inspect for ulcers, calluses, skin changes, and deformities that predispose them to ulceration and to assess sensation and perfusion r5
    • American Diabetes Association recommends comprehensive foot examination at least annually; for patients who have a history of prior ulceration or amputation or who have evidence of sensory loss, inspect feet at every visit r17
    • Examine skin for color changes, dryness, cracking, maceration, and tinea pedis
    • Check for calluses, blisters, and ulcers
    • Note structural abnormalities (eg, Charcot arthropathy, bunions, hammer toes) that are subject to pressure and friction
    • Check sensation with a 10-g monofilament on plantar aspects of the hallux and on first, third, and fifth metatarsal heads. Also assess 1 or more of the following neurologic parameters, as reduced response may signal onset of neuropathy:
      • Vibration (128-Hz tuning fork) on plantar surface of the hallux
      • Pinprick sensation on the dorsal surface of the hallux just proximal to the nail
      • Ankle (Achilles tendon) reflexes
    • Assess perfusion
      • Palpate pulses
      • In patients who have weak dorsalis pedis or posterior tibial pulses, obtain an ankle-brachial index
        • Place blood pressure cuff above the ankle and measure systolic blood pressure in the dorsalis pedis and/or posterior tibial artery, with the aid of a handheld Doppler, if necessary
        • Divide result by brachial systolic value to calculate ankle-brachial index r3r5
          • Reference range is 0.91 to 1.3
          • 0.6 to 0.89 indicates mild perfusion deficit and may be associated with claudication
          • 0.4 to 0.59 indicates moderate obstruction to perfusion
          • Less than 0.4 indicates severely reduced flow and may be associated with rest pain
          • More than 1.3 indicates arterial calcification and is an unreliable indicator of perfusion
    • Inspect shoes inside and out for areas of wear, rough interior surfaces, foreign bodies r2
      • Assess for proper fit while patient stands wearing shoe
        • Inside shoe length should be 1 to 2 cm longer than foot
        • Inside shoe width should accommodate widest point, usually across metatarsal heads
        • Height of toe box should accommodate without rubbing tops of all toes
      • Assess need for orthotic device or prescription shoe to accommodate deformities
  • Various risk classifications are used to guide recommendations for how to prevent foot ulcers including frequency of follow-up and protective measures r5
    • Risk stratification and guidance developed by American Diabetes Association is as follows:
      • Risk category 0: no loss of protective sensation, no peripheral vascular disease, and no deformity
        • Provide patient education and advice about appropriate footwear
        • Ideally, perform annual assessment
      • Risk category 1: loss of protective sensation with or without structural deformity
        • Consider prescriptive footwear
        • Consider surgical correction of deformity if footwear cannot be designed to accommodate it
        • Reinforce education
        • Reassess every 3 to 6 months
      • Risk category 2: peripheral artery disease with or without loss of protective sensation
        • Consider prescriptive footwear
        • Consider consulting and ongoing follow-up with a vascular specialist
        • Reassess every 2 to 3 months
      • Risk category 3: history of ulcer or amputation
        • Provide patient education and advice about appropriate footwear
        • If peripheral vascular disease is present, consider consultation and ongoing follow-up with a vascular specialist
        • Reassess every 1 to 2 months
    • Similar risk assessments and recommendations are also provided by Society for Vascular Surgery/American Podiatric Medical Association/Society for Vascular Medicine,r8National Institute for Health and Care Excellence,r14 and International Working Group on the Diabetic Footr2
  • Elements of patient education should include the following: r2
    • Daily foot inspection—including web spaces—by patient or caregiver
      • Notify health care provider immediately if there is a new wound of any kind, or if foot appears red or feels unusually warm
    • Foot care/hygiene
      • Wash feet daily, avoiding water that is higher than body temperature; dry carefully, including between toes
      • Lubricate dry skin with emollients, but avoid areas between toes
      • Do not attempt to remove calluses yourself; consult your health care provider
      • Cut toenails straight across; if unable (eg, inadequate vision, impaired mobility), get help from caregiver or professional
    • Appropriate footwear
      • Do not walk barefoot, wear only socks, or wear thin slippers without protective soles; do wear shoes inside and outside of home
      • Do not wear shoes that are too tight or that have irregular inside surfaces that rub the skin
      • Inspect shoes and feel inside with hand to identify roughness or foreign objects before putting on shoe
      • Wear seamless socks and change daily to a clean pair; do not wear tight or knee socks
    • Do not use any kind of heating device to warm feet
    • Be sure that your health care provider examines your feet regularly
  • Tight glycemic control (for most patients, target hemoglobin A1C less than 7%) may delay development or slow progression of diabetic neuropathy and therefore of diabetic foot ulcers r17
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