Elsevier LogoDiabetes

    ThisiscontentfromClinicalKey

    Diabetic foot infection

    Sign up for your free ClinicalKey trial today!  Your first step in getting the right answers when you need them.

    Start Free Trial
    Feb.12.2024

    Diabetic Foot Infection

    Synopsis

    Key Points

    • Diabetic foot infection is an infection, often originating from an ulcer, that occurs in a patient with diabetes
      • 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, and calor
      • May be accompanied by systemic indicators of infection such as fever or hypothermia, tachycardia, or tachypnea
    • Diagnosis is clinical, based on the presence of local and systemic signs and symptoms of inflammation
      • Obtain a CBC, serum chemistry study, and erythrocyte sedimentation rate, C-reactive protein level, or procalcitonin level for all patients whose clinical examination findings suggest infection
      • Obtain deep cultures after thorough cleansing and preliminary debridement
      • Assess vascular status in all patients (eg, symptoms of claudication, pedal pulses), including ankle-brachial index when indicated
      • For suspected osteomyelitis or Charcot arthropathy, begin with plain radiographs and utilize MRI or other forms of imaging if radiographs are nondiagnostic
    • Infection may be classified as follows according to the Infectious Diseases Society of America and the International Working Group on the Diabetic Foot:
      • Uninfected (grade 1): no symptoms or signs of infection
      • Mild (grade 2): infection confined to skin and subcutaneous tissue; erythema, if present, extends no further than 2 cm around the ulcer
      • Moderate (grade 3): infection extending beneath subcutaneous tissue or erythema exceeding a 2-cm rim around the ulcer
      • Severe (grade 4): local infection 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 infection
      • 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; approximately 20% of moderate to severe infections require amputation; in the remainder, healing is often very slow and/or incomplete r1
    • 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 caregivers 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
    • Differentiating between soft tissue infection, osteomyelitis, and Charcot osteoarthropathy may be difficult and require multimodal imaging r2

    Terminology

    Clinical Clarification

    • Diabetic foot infection is an infection, often originating from an ulcer, that occurs in a patient with diabetes
      • 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 approximately 20% of diabetic foot infections r3

    Classification

    • Many diabetic foot ulcer classifications exist r4r5
    • IDSA (Infectious Diseases Society of America) and IWGDF (International Working Group on the Diabetic Foot) classification consists of 4 grades of severity for diabetic foot infection, ranging from uninfected to severe infection; these correspond to the IWGDF PEDIS (perfusion, extent, depth, infection, and sensation) grades 1 through 4 r6
      • Scores for both scales are based on signs, symptoms, and extent of local infection and on the presence or absence of signs of systemic infection
        • Used to determine which patients require hospital admission for IV administration of antibiotics
      • Uninfected (grade 1): no symptoms or signs of infection
        • No purulence or inflammation
      • Mild (grade 2): infection confined to skin and subcutaneous tissue
        • 2 or more of the following manifestations of inflammation:
          • Purulence
          • Erythema (between 0.5 and 2 cm around an ulcer)
          • Tenderness
          • Warmth
          • Induration
        • No other local complications or systemic illness
      • Moderate (grade 3): infection extending beneath subcutaneous tissue or erythema exceeding a 2-cm rim around the ulcer
        • 1 or more of the following:
          • Cellulitis extending more than 2 cm
          • Lymphangitic streaking
          • Spread beneath the superficial fascia
          • Deep tissue abscess
          • Gangrene
          • Involvement of muscle, tendon, joint, or bone
        • Patient is systemically well and metabolically stable
      • Severe (grade 4): local infection with signs of systemic involvement
        • Patient has signs of systemic toxicity or metabolic instability with 2 or more of the following: r6
          • Fever or chills (temperature higher than 38 °C or lower than 36 °C)
          • Tachycardia (more than 90 beats per minute)
          • Hypotension
          • Confusion
          • Vomiting
          • Leukocytosis (WBC count greater than 12,000/mm³ or less than 4000/mm³, or more than 10% immature [band] forms)
          • Acidosis
          • Severe hyperglycemia
          • Azotemia
          • Tachypnea (more than 20 breaths per minute) or partial pressure of carbon dioxide less than 32 mm Hg
    • Another classification schema is the Wound, Ischemia, and Foot Infection system, recommended as an alternative to IDSA/IWGDF classification where resources permit r6
      • Assesses 1-year risk for amputation and 1-year benefit for revascularization based on combination of scores for the following:
        • Wound (based on depth of ulcer or extent of gangrene)
        • Ischemia (based on ankle pressure, toe pressure, or transcutaneous oxygen pressure)
        • Foot infection (based on the IDSA/IWGDF criteria)

    Diagnosis

    Clinical Presentation

    History

    • Clinical presentation varies, depending on extent and duration of infection and patient's degree of sensory impairment
      • Patients with advanced diabetic neuropathy may not experience pain, even in the presence of a severe infection; those with impaired vision (eg, severe retinopathy) may not be able to see signs of infection to report them
    • Pain may be a presenting symptom in patients who can perceive it
    • Fever or chills may occur, as may other systemic symptoms such as nausea or vomiting
    • Because 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 symptoms reported on presentation, 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 have hypothermia, tachycardia, tachypnea, and/or hypotension
    • Foot examination
      • Assess for infection, defined by the 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 red 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
          • Size of the ulcer
        • 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; a handheld Doppler device may aid in identifying the 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, which causes structural changes and results in weight-bearing shifts, callus formation, and friction
    • Other breaks in skin integrity, including traumatic wounds and tinea pedis, may also 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 r7
      • Staphylococci (including MRSA) and streptococci are most common
      • Aerobic gram-negative bacilli (eg, Escherichia coli) are frequently involved, especially in patients who have previously received antibiotics
      • Anaerobes may play a role in ischemic or necrotic tissue

    Risk factors and/or associations

    Other risk factors/associations
    • Limb ischemia due to peripheral artery disease increases the risk of a diabetic foot ulcer becoming infected r5
    • Risk factors for more severe infection include: r7
      • Wound extending to bone or subcutaneous tissues
      • Extensive or rapidly progressive cellulitis
      • Severe inflammation, induration, crepitus, bullae, discoloration, necrosis, gangrene, ecchymoses, or petechiae
      • New anesthesia or localized pain
      • Foreign body
      • Immunosuppression
      • Systemic signs or symptoms (eg, fever, confusion, hypotension, volume depletion)
      • Rapid progression, or progression despite adequate treatment
    • Risk factors for foot ulcers, a common precursor to diabetic foot infection, include the following: r5r8
      • Foot deformity
      • Peripheral neuropathy with loss of protective sensation
      • Peripheral vascular disease
      • Poor glycemic control
      • Diabetic nephropathy
      • Visual impairment
      • Previous foot ulcer
      • Previous amputation
      • Cigarette smoking
      • Calluses or corns
      • Chronic kidney disease

    Diagnostic Procedures

    Primary diagnostic tools

    • Clinical diagnosis is based on the presence of local signs and symptoms of inflammation, with or without systemic signs
    • 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 r7
          • Gently insert a blunt sterile metal probe through the wound to determine if the wound is through to the bone (detected by hard, gritty feel)
          • This test can help diagnose (when likelihood is high) or rule out (when likelihood is low) osteomyelitis
    • Obtain specimens from infected wounds for culture after cleaning and debridement r7
      • Do not obtain specimens for culture from clinically uninfected wounds
      • Collect tissue specimens for culture by aspiration of the abscess, curettage from the ulcer, or biopsy of deep tissue during surgical procedure; do not use superficial swab r7r9
      • For patients with suspected osteomyelitis, arrange for bone biopsy to obtain specimens for culture and histopathology
    • Inflammatory markers (eg, erythrocyte sedimentation rate, C-reactive protein, or procalcitonin) can be a useful adjunctive measure for establishing the diagnosis when examination findings are equivocal r7
      • Obtain CBC and serum chemistry studies to help determine risk for severe infection or need for hospitalization r7
    • Assess severity of infection using classification scheme from the Infectious Diseases Society of America/International Working Group on the Diabetic Foot or the WIfI classification (Wound, Ischemia, foot Infection) r6
      • Based on extent and depth of infection and presence of systemic signs of infection
      • Can guide choice of empiric antibiotic regimen and route of administration and help determine need for hospitalization
    • Obtain ankle-brachial index or toe-brachial index to assess vascular supply, particularly for patients with nonpalpable or weak distal pulses r5
      • Further evaluation of vascular supply (eg, angiography) may be indicated for some patients, but usually not immediately
    • Imaging is indicated if an infective complication such as deep abscess, osteomyelitis, or foreign body or an alternative diagnosis of Charcot arthropathy is suspected r2r5
      • Plain radiographs are recommended for all patients as the initial study, but radiographs may be nondiagnostic early in the infection course r7r10r11
      • If plain radiographs are not revealing when Charcot arthropathy is suspected, order MRI or CT scan and/or a radionucleotide scan if MRI is unavailable r5
      • MRI is the most sensitive study for detecting osteomyelitis, especially early in the infection course; can detect soft tissue abscess r7r11
      • If MRI cannot be done, CT, bone scan, or a radionuclide-labeled WBC scan with/without SPECT (single-photon emission computed tomography) or SPECT/CT is recommended when osteomyelitis is suspected r7r12

    Laboratory

    • CBC
      • Elevated WBC count supports the diagnosis of infection, but a value within reference range does not rule it out
        • Criteria for severe infection include the following: r13
          • WBC counts lower than 4000 cells/mm³
          • WBC counts higher than 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 r14
      • 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
      • Rate 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 level of 3.2 mg/dL or higher r15
    • 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 erythrocyte sedimentation rate of 60 mm/hour or higher r15
    • Procalcitonin
      • Elevated procalcitonin level, especially in conjunction with an elevated C-reactive protein level, can help discriminate infection from other conditions (eg, noninfected ulcer) r7r16
    • Cultures
      • Deep cultures of soft tissue, obtained by biopsy or curettage after debridement and lavage, may identify the infecting organism(s) most accurately r7

    Imaging r2r12

    • Plain radiograph of foot
      • Useful in further defining bony deformities (Charcot foot) and may show 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) r3
      • For patients whose imaging study findings are initially negative, serial radiographs during course of treatment are recommended to enable early detection of developing osteomyelitis r10
    • MRI of foot
      • Most sensitive and specific imaging test for diagnosing osteomyelitis and defining extent of disease r17
      • Normal marrow signal essentially excludes diagnosis of osteomyelitis
    • CT of foot r12r17
      • Can be used to assess bone and joint involvement adjacent to diabetic foot ulcers
      • Shows characteristic changes associated with osteomyelitis more clearly than plain radiographs but is less sensitive for infection than MRI r12r17
    • Radionuclide-labeled WBC scan
      • May be done in conjunction with 3-phase bone scan and/or SPECT (single-photon emission computed tomography) or SPECT/CT of foot r12
      • 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, findings on scans may be positive or indeterminant, but a negative finding excludes the diagnosis of osteomyelitis

    Procedures

    Bone biopsy r7r18
    General explanation
    • Sampling of bone for histopathologic examination and microbiologic culture
    • Specimens may be obtained via surgical or percutaneous bone biopsy or during debridement
      • In stable patients, in whom there is minimal soft tissue infection, ideally obtain specimens before initiating antibiotic therapy
      • For patients with significant soft tissue infection, do not delay antimicrobial therapy
      • Ideally, perform percutaneous biopsy through intact skin to reduce culture contamination; however, biopsy is often performed through the ulcer in practice r18
    • Perform both aerobic and anaerobic cultures on biopsy specimens
    Indication
    • Perform for 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 shows necrotic bone and inflammatory exudate
    • Culture results identify causative pathogens and show antimicrobial susceptibility pattern

    Other diagnostic tools

    • Ankle systolic pressure and ankle-brachial index r5
      • Recommended for all patients with diabetic foot infection or ulcer, especially if pulses are diminished or absent
      • Accuracy in predicting peripheral artery disease is variable, especially in the presence of neuropathy or arterial calcification, but the test is noninvasive, easy to do, and requires no special equipment r19
        • Place blood pressure cuff above ankle and measure ankle systolic blood pressure (dorsalis pedis and/or posterior tibial artery) with the aid of a handheld Doppler device r5
          • Also evaluate pedal Doppler arterial waveforms, which should be triphasic r5
        • Divide result by brachial systolic value to calculate the ankle-brachial index r5
          • Traditional ankle-brachial index uses the higher of either dorsalis pedis or posterior tibial pressure (or the average of the two) divided by the higher of left or right brachial pressure, which provides the most optimistic measure of blood flow to the foot r5
          • For patients with diabetes, guidelines recommend using the lower of the dorsalis pedis or posterior tibial pressures divided by the higher of the left or right brachial pressure to diagnose peripheral artery disease, particularly as peripheral arterial disease may only affect one artery r5
          • Reference range is 0.90 to 1.3: peripheral arterial disease is unlikely r20
          • Greater than 1.3 indicates arterial calcification and is an unreliable indicator of perfusion; use toe-brachial index instead r20
    • Toe systolic pressure and toe-brachial index r5
      • Requires toe pressure cuff and handheld Doppler device
      • Wrap toe cuff around great toe and measure systolic pressure using Doppler device placed distal and medial to the cuff
      • Pressure lower than 30 mm Hg indicates significantly impaired perfusion
      • Divide result by brachial systolic value to calculate the toe-brachial index r5
        • Peripheral arterial disease is unlikely with toe-brachial index of 0.75 or greater
    • Skin perfusion pressure and transcutaneous oxygen pressure
      • Require special equipment but help assess prognosis
      • Skin perfusion pressure less than 40 mm Hg or a transcutaneous oxygen pressure of less than 25 mm Hg increases the likelihood of poor healing and amputation r3r20r21

    Differential Diagnosis

    Most common

    • Acute Charcot arthropathy r22
      • 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) 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 for 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 show 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

    Admission is based on a combination of severity according to Infectious Diseases Society of America/International Working Group on the Diabetic Foot criteria and individual patient circumstances

    • Admit patients with severe diabetic foot infection or moderate diabetic foot infection that is complex or associated with significant comorbidities or lack of outpatient support r7
    Criteria for ICU admission
    • Severe infection (eg, gangrene, necrotizing fasciitis) and hemodynamic instability or associated severe metabolic derangements (eg, diabetic ketoacidosis)

    Recommendations for specialist referral

    • Specialist teams, where available, are recommended r23r24
    • 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 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 a podiatrist for proper protective and offloading device to avoid pressure or friction on the affected area

    Treatment Options

    Cleanse and debride wounds or ulcers r5

    • Debridement is usually done surgically, but in some cases, mechanical (eg, wet-to-dry dressings), autolytic, or combination debridement is appropriate r25
      • Serial debridement may be necessary
    • Drain deep collections; decompress compartments under pressure r5

    Treat all patients with empiric antibiotics r5

    • No single regimen has proven superior; select antibiotics based on: r7
      • Severity of infection
      • Likely or proven infectious pathogens and their antibiotic susceptibilities
      • Risk of adverse events and drug interactions
      • Patient factors such as allergies, recent hospitalization, kidney disease
      • Practical considerations such as cost, availability, and experience of the treatment team
    • Parenteral antibiotics are indicated for initial treatment of patients with a severe diabetic foot infection; switch to oral therapy if patient shows clinical improvement and an appropriate oral agent is available
    • Oral antibiotics are appropriate for most mild and some moderate infections at presentation r11
    • For mild to moderate infections in patients who have not recently received antibiotics (for this or other infections), use a regimen aimed at gram-positive cocci r7
      • For patients who have received antibiotics recently, use additional coverage for gram-negative bacilli
    • For severe infections, use antibiotic therapy effective against gram-positive cocci and gram-negative rods r7
      • Add coverage for strict anaerobes in the presence of necrosis, gas formation, or an ischemic limb
    • Empiric coverage of MRSA is recommended in the following circumstances: r7
      • Infection or colonization 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 for which delayed coverage while awaiting culture findings is thought to pose an unacceptable risk to the patient
    • Consider coverage of Pseudomonas aeruginosa for patients with severe infection or macerated wounds and in circumstances that foster its role as a pathogen (eg, warm, moist climate; frequent use of foot soaks) r7
    • The following agents may be used for empiric treatment of diabetic foot infections: r7
      • For mild infection in which MRSA is unlikely to play a role
        • Dicloxacillin or other penicillinase-resistant penicillin
        • Cephalexin or other first-generation cephalosporin
        • For β-lactam allergy or intolerance: clindamycin, levofloxacin or moxifloxacin, trimethoprim-sulfamethoxazole, or doxycycline
        • If recent antibiotic exposure is reported, levofloxacin or moxifloxacin, amoxicillin-clavulanate or ampicillin-sulbactam, or trimethoprim-sulfamethoxazole
      • For mild infection with risk factors for MRSA
        • Linezolid
        • Trimethoprim-sulfamethoxazole
        • Clindamycin
        • Doxycycline
        • Levofloxacin or moxifloxacin
      • For moderate or severe infections without risk factors for MRSA or Pseudomonas aeruginosa infection
        • Amoxicillin-clavulanate
        • Ampicillin-sulbactam
        • Cefuroxime or other second-generation cephalosporin
        • Ceftriaxone, cefotaxime, or other third-generation cephalosporin
      • For moderate or severe infections with recent antibiotic exposure
        • Piperacillin-tazobactam
        • Cefuroxime or other second-generation cephalosporin
        • Ceftriaxone, cefotaxime, or other third-generation cephalosporin
        • Ertapenem
      • For moderate to severe infections in presence of limb ischemia, necrosis, or gas formation
        • Ampicillin-sulbactam or amoxicillin-clavulanate
        • Piperacillin-tazobactam
        • Second- or third-generation cephalosporin plus clindamycin or metronidazole
        • Ertapenem, meropenem, or imipenem-cilastatin
      • For moderate to severe infections with risk for Pseudomonas aeruginosa
        • Piperacillin-tazobactam
        • Penicillinase-resistant penicillin plus ceftazidime or ciprofloxacin
        • Meropenem or imipenem-cilastatin
      • For moderate or severe infections with MRSA risk, add or substitute 1 of the following:
        • Vancomycin or other glycopeptides
        • Linezolid
        • Daptomycin
        • Trimethoprim-sulfamethoxazole
        • Doxycycline
        • Fusidic acid (not available in the United States)
      • For moderate or severe infections with risk for resistant gram-negative rods
        • Ertapenem, meropenem, or imipenem-cilastatin
        • Ciprofloxacin
        • Amikacin
        • Colistin
    • National Institute for Health and Care Excellence provides antibiotic recommendations appropriate for the United Kingdom r24
    • When culture results are available, modify antibiotic regimen accordingly, if indicated
    • 1 to 2 weeks of antibiotics are sufficient for most soft tissue infections; continued treatment for up to 3 to 4 weeks is recommended if the infection is extensive or resolving more slowly than expected or if patient has severe underlying peripheral artery disease r7r11
    • For osteomyelitis, regimens are similar to those for moderate to severe infection, and usual treatment course is 3 to 6 weeks r7d2
      • If infected bone has been completely resected, antibiotic therapy can be given for 2 to 5 days if there is no soft tissue infection
      • If infected bone has been completely resected but soft tissue infection remains, treat for 1 to 2 weeks
      • If the infected bone has been completely resected, but findings on culture or histologic analysis of bone margins are positive, treat for 3 weeks
      • When no surgery is performed or there is necrotic bone, treat for 6 weeks
      • Longer-term suppressive antibiotic therapy is usually not indicated but may be warranted for patients with retained orthopedic hardware or extensive necrotic bone that is not amenable to complete debridement

    Adjunctive therapy

    • Meticulous wound care is an essential part of treatment and involves the following:
      • Application of dressings to protect the wound and maintain a moist environment
      • Offloading of pressure from the wound, particularly when the plantar surface is involved r25
    • Early revascularization may be required to restore adequate blood supply for treatment of infection (delivery of antibiotics and host defenses) r7r20
    • Optimize glycemic control d3
      • Hyperglycemia in hospitalized patients is defined as blood glucose levels higher than 140 mg/dL r23
      • Once insulin therapy is started, a target glucose range of 140 to 180 mg/dL is recommended for most critically ill and noncritically ill patients r23
        • A more stringent goal of 110 to 140 mg/dL may be appropriate for select critically ill patients if achieved without significant hypoglycemia r23
        • In noncritical care settings, a glucose level of 100 to 180 mg/dL is recommended for inpatient management of hyperglycemia r23
    • The following measures are not routinely recommended: r7
      • Granulocyte colony stimulating factor r24r25
      • Topical antiseptics, silver preparations, honey, bacteriophage therapy
      • Negative pressure wound therapy
      • Hyperbaric oxygen therapy or topical oxygen therapy
      • Topical antibiotics (eg, sponge, cream, cement) in addition to systemic antibiotics

    Drug therapy

    • Penicillins
      • Dicloxacillin
        • Dicloxacillin Sodium Oral capsule; Adults: 500 mg PO 4 times daily for 7 to 14 days. Continue treatment for up to 28 days if needed.
      • Amoxicillin-clavulanate
        • Amoxicillin Trihydrate, Clavulanate Potassium Oral tablet; Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
      • 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 every 6 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
      • 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 or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 to 8 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
    • Cephalosporins
      • Cephalexin
        • Cephalexin Monohydrate Oral capsule; Adults: 500 mg PO every 6 hours for 7 to 14 days. Up to 4 g/day may be used. Continue treatment for up to 28 days if needed.
      • Cefuroxime
        • Cefuroxime Sodium Solution for injection; Adults: 1.5 g IV every 6 to 8 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
      • Cefotaxime
        • Cefotaxime Sodium Solution for injection; Adults: 1 to 2 g IV every 8 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
      • Ceftriaxone
        • Ceftriaxone Sodium Solution for injection; Adults: 1 to 2 g IV every 24 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
      • Ceftazidime
        • Ceftazidime Sodium Solution for injection; Adults: 2 g IV every 8 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
    • Carbapenems
      • Ertapenem
        • Ertapenem Solution for injection; Adults: 1 g IV/IM every 24 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
      • 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 for 7 to 14 days. Continue treatment for up to 28 days if needed.
      • Meropenem
        • Meropenem Solution for injection; Adults: 500 mg to 1 g IV every 8 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
    • Fluoroquinolones
      • Levofloxacin
        • Levofloxacin Oral tablet; Adults: 750 mg PO every 24 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
        • Levofloxacin, Dextrose Solution for injection; Adults: 750 mg IV every 24 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
      • Moxifloxacin
        • Moxifloxacin Hydrochloride Oral tablet; Adults: 400 mg PO every 24 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
        • Moxifloxacin Hydrochloride Solution for injection; Adults: 400 mg IV every 24 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
      • Ciprofloxacin
        • Ciprofloxacin Hydrochloride Oral tablet; Adults: 500 to 750 mg PO every 12 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
        • Ciprofloxacin, Dextrose Solution for injection; Adults: 400 mg IV every 8 to 12 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
    • Sulfonamide
      • Trimethoprim-sulfamethoxazole
        • Sulfamethoxazole, Trimethoprim Oral tablet; Adults: 160 to 320 mg trimethoprim/800 to 1,600 mg sulfamethoxazole IV every 12 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
    • Lincosamide
      • Clindamycin
        • Oral dosage
          • Clindamycin Hydrochloride Oral capsule; Adults: 150 to 450 mg PO every 6 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
        • IV/intramuscular dosage
          • Clindamycin Solution for injection; Adults: 600 mg IV/IM every 8 hours to 900 mg IV every 8 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
    • Aminoglycoside
      • Amikacin
        • Amikacin Sulfate Solution for injection; Adults: 15 to 20 mg/kg/dose IV/IM every 24 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
    • Tetracycline
      • Doxycycline
        • Oral dosage
          • Doxycycline Hyclate Oral capsule; Adults: 200 mg PO on day 1, then 100 to 200 mg PO once daily for 7 to 14 days. Continue treatment for up to 28 days if needed.
        • IV dosage
          • Doxycycline Hyclate Solution for injection; Adults: 200 mg IV on day 1, then 100 to 200 mg/day IV with the 200 mg/day dose divided every 12 to 24 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
    • Glycopeptide
      • Vancomycin
        • Vancomycin Hydrochloride Solution for injection; Adults: 15 to 20 mg/kg/dose (Max: 2,000 mg/dose) IV every 8 to 12 hours for 7 to 14 days; adjust dose based on target PK/PD parameter. Continue treatment for up to 28 days if needed.
    • Oxazolidinone
      • Linezolid
        • Oral dosage
          • Linezolid Oral tablet; Adults: 600 mg PO every 12 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
        • IV dosage
          • Linezolid Solution for injection; Adults: 600 mg IV every 12 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
    • Lipopeptide
      • Daptomycin
        • Daptomycin Solution for injection; Adults: 4 mg/kg/dose IV every 24 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
    • Nitroimidazole
      • Metronidazole
        • Oral dosage
          • Metronidazole Oral tablet; Adults: 500 mg PO every 6 to 8 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.
        • IV dosage
          • Metronidazole Solution for injection; Adults: 500 mg IV every 6 to 8 hours for 7 to 14 days. Continue treatment for up to 28 days if needed.

    Nondrug and supportive care

    Wound care

    • Numerous studies have sought to identify the optimal dressing, although most studies have been done with patients with noninfected diabetic foot ulcers; in that setting, no superior dressing has been identified. r27r26
      • In general, dressings are selected for wound protection, moisture management, pain reduction, aesthetics, and compatibility with offloading and immobilization needs r28
        • Wounds that are too dry cause cell death and prevent epithelial migration and matrix deposition; excessive moisture, such as from exudate, will inhibit cell proliferation and break down matrix
    • Offloading (ie, preventing pressure on the affected area) allows progressive healing, but it must be balanced with need for frequent dressing changes and wound inspections r29
      • Nonremovable knee-high offloading devices (eg, total contact casts or nonremovable walkers) are the first choice for offloading treatment of noninfected foot ulcers, neuropathic plantar forefoot or midfoot diabetic foot ulcers, and those with either mild infection or mild ischemia r29
        • Avoid nonremovable offloading devices when heavy exudate is present due to need for frequent wound care r29
      • Consider removable offloading devices (either knee-high or ankle-high) as second line option r29
        • They are acceptable for patients with both mild infection and mild ischemia or those with either moderate infection or moderate ischemia
        • May also be considered for patients with both moderate infection and moderate ischemia or with either severe infection or severe ischemia, depending on patient's functional status and activity level
    • Other treatments that have not shown clear benefit and that are not currently routinely recommended for diabetic foot infections include hyperbaric oxygen; topical oxygen; negative pressure wound therapy; sucrose-octasulfate–impregnated dressings; autologous combined leukocyte, platelet, and fibrin patches; and topical placental-derived products r7r24
      • These treatments have been shown to help heal diabetic foot ulcers and may be considered to help heal certain refractory ulcers once infection is resolved r30
    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) and chemical (eg, dressings that promote autolysis) debridement
    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
    • Many patients with diabetes also have ischemic heart disease, which may increase risk associated with surgical procedures

    Monitoring

    • Inspect infected wounds frequently, daily during hospitalization
      • 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 d4
    • Contiguous spread to bone or joint may lead to osteomyelitis or septic arthritis r31
    • 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 d5

    Prognosis

    • Both short- and long-term prognoses are guarded
      • Approximately 20% of moderate to severe infections require amputation at some level r1
      • At 1-year follow-up in a large series of patients with infected diabetic foot ulcers, 64% of patients (96 of 150) had experienced resolution of infection and complete wound healing r32
        • 19% required amputation, and 12% died in the 12 months following hospital discharge
      • Overall mortality at 5 years after an amputation for diabetic foot infection is 70% r1
      • Osteomyelitis is associated with more surgical procedures and amputations, longer hospitalizations, and higher rates of recurrent infection and readmission for infection compared with moderate and severe diabetic foot infection involving soft tissue only r33
        • More than 80% of patients with diabetic foot osteomyelitis require amputation r18
    • For an individual patient, favorable prognostic markers include the following: r20
      • Toe pressure of 30 mm Hg or higher
      • Skin perfusion pressure of 40 mm Hg or higher
      • Transcutaneous oxygen pressure of 25 mm Hg or higher

    Screening and Prevention

    Prevention

    • A foot ulcer is a common precursor to infection, and all patients with diabetes should have their feet examined regularly to detect ulcers, calluses, skin changes, and deformities that predispose them to ulceration and to assess sensation and perfusion r8
      • 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 r8
      • 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 because 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
        • Temperature
      • Assess perfusion
        • Palpate lower-extremity pulses and check capillary refill time, rubor on dependency, pallor on elevation, and venous filling time r8
        • For patients with history of leg fatigue, claudication, or rest pain relieved with dependency and those who have weak or absent dorsalis pedis or posterior tibial pulses, obtain an ankle-brachial index r8
      • Inspect shoes inside and out for areas of wear, rough interior surfaces, foreign bodies r5
        • 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 any of the 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 r34
      • Risk stratification and guidance developed by American Diabetes Association are 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 the Society for Vascular Surgery/American Podiatric Medical Association/Society for Vascular Medicine,r10National Institute for Health and Care Excellence,r24 and International Working Group on the Diabetic Footr34
    • Elements of patient education should include the following: r5
      • 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 use chemical agents or plasters to remove corns or calluses; consult your health care professional
        • Cut toenails straight across; if unable to do so (eg, inadequate vision, impaired mobility), get help from caregiver or professional
      • Appropriate footwear
        • Do not walk barefoot or wear only socks or thin slippers without protective soles; wear shoes inside and outside home
        • Do not wear shoes that are too tight or 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 socks or knee socks
      • Do not use any kind of heating device to warm feet
      • Be sure that your health care professional examines your feet regularly
    • Tight glycemic control may delay development or slow progression of diabetic neuropathy and diabetic foot ulcers r35
    Armstrong DG et al: Diabetic foot ulcers and their recurrence. N Engl J Med. 376(24):2367-75, 201728614678Lauri C et al: Diabetic foot infections: the diagnostic challenges. J Clin Med. 9(6):1779, 202032521695Fridman R et al: Imaging of diabetic foot infections. Clin Podiatr Med Surg. 31(1):43-56, 201424296017Hamilton EJ et al: Australian guideline on wound classification of diabetes-related foot ulcers: part of the 2021 Australian evidence-based guidelines for diabetes-related foot disease. J Foot Ankle Res. 14(1):60, 202134861898Schaper NC et al: Practical guidelines on the prevention and management of diabetes-related foot disease (IWGDF 2023 update). Diabetes Metab Res Rev. e3657, 202337243927Monteiro-Soares M et al: Guidelines on the classification of foot ulcers in people with diabetes (IWGDF 2023 update). Diabetes Metab Res Rev. e3648, 202337179483Senneville É, et al. Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF/IDSA 2023). IWGDF website. Accessed July 14, 2023. https://iwgdfguidelines.org/infection-guideline-2023/https://iwgdfguidelines.org/infection-guideline-2023/American Diabetes Association Professional Practice Committee: 12. Retinopathy, neuropathy, and foot care: standards of care in diabetes-2024. Diabetes Care. 47(suppl 1):S231-43, 202438078577Doğruel H et al: Management of diabetic foot ulcers and the challenging points: an endocrine view. World J Diabetes. 13(1):27-36, 202235070057Hingorani A et al: The management of diabetic foot: a clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine. J Vasc Surg. 63(2 suppl):3S-21S, 201626804367Matheson EM et al: Diabetes-related foot infections: diagnosis and treatment. Am Fam Physician. 104(4):386-94, 202134652105Expert Panel on Musculoskeletal Imaging et al: ACR Appropriateness Criteria suspected osteomyelitis of the foot in patients with diabetes mellitus. J Am Coll Radiol. 16(11S):S440-50, 201931685111Monteiro-Soares M et al: Guidelines on the classification of diabetic foot ulcers (IWGDF 2019). Diabetes Metab Res Rev. 36 suppl 1:e3273, 202032176445Korytkowski MT et al: Management of hyperglycemia in hospitalized adult patients in non-critical care settings: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. ePub, 202235690958Fleischer AE et al: Combined clinical and laboratory testing improves diagnostic accuracy for osteomyelitis in the diabetic foot. J Foot Ankle Surg. 48(1):39-46, 200919110158Velissaris D et al: Procalcitonin as a diagnostic and prognostic marker in diabetic foot infection. A current literature review. Rom J Intern Med. 56(1):3-8, 201829028632Li S et al: Imaging in chronic wound diagnostics. Adv Wound Care (New Rochelle). 9(5):245-63, 202032226649Schechter MC et al: Percutaneous bone biopsy for diabetic foot osteomyelitis: a systematic review and meta-analysis. Open Forum Infect Dis. 7(10):ofaa393, 202033134407Brownrigg JR et al: Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: a systematic review. Diabetes Metab Res Rev. 32 suppl 1:119-27, 201626342170Fitridge R, et al. The intersocietal IWGDF, ESVS, SVS guidelines on the diagnosis, prognosis and management of peripheral artery disease in patients with diabetes mellitus. IWGDF website. Accessed July 14, 2023. https://iwgdfguidelines.org/pad-guideline-2023/https://iwgdfguidelines.org/pad-guideline-2023/Elraiyah T et al: A systematic review and meta-analysis of off-loading methods for diabetic foot ulcers. J Vasc Surg. 63(2 Suppl):59S-68S.e1-2, 201626804369Wukich DK et al: Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus (IWGDF 2023). Diabetes Metab Res Rev. e3646, 202337218537American Diabetes Association Professional Practice Committee: 16. Diabetes care in the hospital: standards of care in diabetes-2024. Diabetes Care. 47(suppl 1):S295-306, 202438078585National Institute for Health and Care Excellence: Diabetic Foot Problems: Prevention and Management. NICE guideline NG19. NICE website. Published August 26, 2015. Updated October 11, 2019 . Accessed July 14, 2023. https://www.nice.org.uk/guidance/ng19https://www.nice.org.uk/guidance/ng19Pérez-Panero AJ et al: Prevention, assessment, diagnosis and management of diabetic foot based on clinical practice guidelines: a systematic review. Medicine (Baltimore). 98(35):e16877, 201931464916Wu L et al: Dressings for treating foot ulcers in people with diabetes: an overview of systematic reviews. Cochrane Database Syst Rev. 7:CD010471, 201526171906Lipsky BA et al: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 54(12):e132-73, 201222619242Eriksson E et al: Chronic wounds: treatment consensus. Wound Repair Regen. 30(2):156-71, 202235130362Bus SA et al: Guidelines on offloading foot ulcers in persons with diabetes (IWGDF 2023 update). Diabetes Metab Res Rev. e3647, 202337226568Chen P et al: Guidelines on interventions to enhance healing of foot ulcers in people with diabetes (IWGDF 2023 update). Diabetes Metab Res Rev. e3644, 202337232034Johani K et al: Understanding the microbiome of diabetic foot osteomyelitis: insights from molecular and microscopic approaches. Clin Microbiol Infect. 25(3):332-9, 201929787888Richard JL et al: Management of patients hospitalized for diabetic foot infection: results of the French OPIDIA study. Diabetes Metab. 37(3):208-15, 201121169044Lavery LA et al: The infected diabetic foot: re-evaluating the Infectious Diseases Society of America diabetic foot infection classification. Clin Infect Dis. 70(8):1573-9, 202031179491Bus SA et al: Guidelines on the prevention of foot ulcers in persons with diabetes (IWGDF 2023 update). Diabetes Metab Res Rev. e3651, 202337302121Lim JZ et al: Prevention and treatment of diabetic foot ulcers. J R Soc Med. 110(3):104-109, 201728116957
    Small Elsevier Logo

    Cookies are used by this site. To decline or learn more, visit our cookie notice.


    Copyright © 2024 Elsevier, its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

    Small Elsevier Logo
    RELX Group