Skin Infections in Diabetes Mellitus

Aka: Skin Infections in Diabetes Mellitus, Diabetic Foot Infection, Cellulitis in Diabetes Mellitus, Cellulitis in Diabetic Foot, Infection of Foot Associated with Diabetes

II. Pathophysiology

  1. Most common organisms are still aerobic Gram Positive Cocci
    1. Staphylococcus aureus is most common cause
    2. Methicillin-Resistant Staphylococcus aureus (MRSA) is present in 10-32% of diabetic infections
  2. Risk factors for polymicrobial infections and especially Gram Negative infections (30-40%)
    1. More common in Chronic Wounds or recent antibiotics
    2. Requires broader spectrum antibiotic use
  3. Risk factors for anaerobic infections
    1. Necrotic wounds
    2. Ischemic foot infections

III. Examination

  1. Evaluate severity of infection
    1. Distribution of infection
    2. Depth of infection
      1. See Probe-to-Bone Test (evaluation for Osteomyelitis)
    3. Associated systemic signs and symptoms
  2. Neurovascular examination
    1. Evaluate for limb ischemia (Peripheral Arterial Disease)
      1. Consider Ankle-Brachial Index
      2. Evaluate distal pulses
      3. Evaluate for pale or cold extremeties
    2. Evaluate for Diabetic Neuropathy
  3. Diabetic control
    1. Metabolic abnormalities

IV. Differential Diagnosis

  1. Local Trauma
  2. Gouty Arthritis
  3. Acute Charcot Neuroarthropathy
  4. Fracture
  5. Deep Venous Thrombosis
  6. Limb Ischemia
  7. Venous Stasis

V. Diagnosis: Local Infection (requires 2 classic findings of inflammation or purulence)

  1. Local redness, warmth, induration, swelling, pain or tenderness
  2. Erythema >0.5 cm around an ulcer in any direction
  3. Purulent drainage
  4. Other findings suggestive of infection
    1. Local wound refractory to standard therapy
    2. Non-purulence persistent drainage
    3. Malodor or friable tissue

VI. Grading: Diabetic Wound Severity (IWGDF Grade or IDSA classification)

  1. Grade 1: Not infected
    1. See diagnostic criteria above
  2. Grade 2: Mild infection
    1. Local infection of skin or subcutaneous tissue or
    2. Erythema around wound site measuring 0.5 to 2 cm
  3. Grade 3: Moderate infection
    1. Local infection extending deeper than subcutaneous tissue (Abscess, Osteomyelitis, Septic Arthritis or fasciitis) or
    2. Erythema around wound site measuring >2 cm
  4. Grade 4: Severe infection
    1. Local infection AND
    2. Systemic Inflammatory Response Syndrome (SIRS)
  5. References
    1. Lipsky (2012) Diabetes Metab Res Rev 28(suppl 1): 163-78 [PubMed]

VII. Labs

  1. Complete Blood Count
    1. Leukocytosis is absent in 50% of cases of Diabetic Foot Infection
    2. Neutrophil Count is normal in over 80% of Diabetic Foot Infections
  2. Erythrocyte Sedimentation Rate or C-Reactive Protein
    1. Erythrocyte Sedimentation Rate >70 mm/hour correlates with Diabetic Foot Infection
  3. Wound culture
    1. Avoid superficial culture swabs due to inaccuracy from contamination
    2. Currettage from debrided ulcer base or obtain deep specimen tissue biopsy

VIII. Imaging: Suspected Osteomyelitis

  1. See Diabetic Foot Osteomyelitis
  2. XRay extremity
    1. See Osteomyelitis XRay
    2. Baseline study observing for local bone destruction, gas formation or foreign body
    3. Poor Test Sensitivity (as low as 25%), especially in early diabetic ulcers or mild infections (under a few weeks in duration)
  3. Bone Scan
    1. See Osteomyelitis Bone Scan
    2. Triple Phase Bone Scan Test Sensitivity for Osteomyelitis 90%, but Specificity is only 46%
    3. White Blood Cell scans increase sensitivity
  4. MRI (preferred)
    1. See Osteomyelitis MRI
    2. Characterizes deep infection involvement
    3. Detects Osteomyelitis (Test Sensitivity 90%)

IX. Management: Cellulitis in comorbid Diabetes Mellitus

  1. Coverage
    1. Streptococcus
    2. Staphylococcus aureus (assume MRSA)
    3. Enterobacteriaceae
    4. Anaerobic Bacteria
  2. Early or Mild disease (2 agent protocol)
    1. Course: 1-2 weeks
    2. Agent 1: MRSA Coverage (choose one)
      1. Trimethoprim-Sulfamethoxazole (Septra, Bactrim) DS one to two tabs orally twice daily (preferred)
      2. Alternative agents in Sulfa Allergy
        1. Minocycline 100 mg orally twice daily
        2. Doxycycline 100 mg orally twice daily
        3. Clindamycin (risk of induced resistance)
    3. Agent 2: Streptococcus coverage (choose one)
      1. Dicloxacillin 50 mg orally four times daily or
      2. Cephalexin 500 mg orally four times daily or
      3. Penicillin VK 500 mg orally four times daily
  3. Severe disease (e.g. fever, systemic symptoms or signs)
    1. Course: 2-3 weeks with initial inpatient parenteral antibiotics
    2. Agent 1: Streptococcus and Enterobacteriaceae (choose one)
      1. Carbapenem (preferred)
        1. Imipenem/Cilastin (Primaxin) 500 mg IV every 6 hours (preferred) or
        2. Ertapenem (Invanz) 1 gram IV q24 hours or
        3. Doripenem 500 mg IV q8 hours or
        4. Meropenem 1 gram IV q8 hours
      2. Alternative agents
        1. Levofloxacin (not recommended due to growing resistance)
        2. Piperacillin-Tazobactam (Zosyn)
        3. Ticarcillin-Clavulanate (Timentin)
    3. Agent 2: MRSA coverage (choose one)
      1. Vancomycin 30 mg/kg IV every 12 hours (first-line for MRSA)
      2. Daptomycin 4 mg/kg IV q24 hours or
      3. Linezolid 600 mg IV or PO every 12 hours or
      4. Tigecycline (Tygacil) 100 mg IV load and then 50 mg IV every 12 hours

X. Management: Diabetic Foot Ulcer

  1. See Suspected Osteomyelitis in Diabetes Mellitus
  2. Wound care
    1. Clense and debride wounds
    2. Probe-to-Bone Test
  3. Antibiotic Course: 7-14 days for mild infections (longer course may be needed in more severe infections)
  4. Isolated Skin Ulcer without inflammation
    1. No antibiotics required
    2. See Diabetic Foot Ulcer for wound management
  5. Ulcer with superficial inflammation (2 agent protocol to cover for Streptococcus and Staphylococcus aureus)
    1. Agent 1: MRSA Coverage (choose one)
      1. Trimethoprim-Sulfamethoxazole (Septra, Bactrim) DS one to two tabs orally twice daily (preferred) or
      2. Doxycyline 100 mg orally twice daily
    2. Agent 2: Streptococcus coverage (choose one)
      1. Augmentin XR 2000/125 orally twice daily or
      2. Cephalexin 500 mg orally every 6 hours or
      3. Cefprozil 500 mg orally every 12 hours or
      4. Cefpodoxime 200 mg every 12 hours or
      5. Cefuroxime 500 mg orally every 12 hours or
      6. Levofloxacin 750 mg orally daily
  6. Ulcer with >2 cm inflammation and fascia extension (to additionally cover for Gram Negative Bacteria; risk of Osteomyelitis)
    1. Oral Protocol 1
      1. Trimethoprim-Sulfamethoxazole (Septra, Bactrim) DS one to two tabs orally twice daily AND
      2. Amoxicillin-Clavulanate (Augmentin) XR 2000/125 orally twice daily
    2. Oral Protocol 2
      1. Linezolid 600 mg orally twice daily AND
      2. Fluoroquinolone (Ciprofloxacin 750 mg twice daily or Levofloxacin 750 mg daily)
    3. Parenteral Protocol (2 agents)
      1. Agent 1: MRSA Coverage (choose 1)
        1. Vancomycin 30 mg/kg IV every 12 hours (first-line for MRSA) or
        2. Linezolid 600 mg orally twice daily or
        3. Daptomycin 6 mg/kg IV q24 hours
      2. Agent 2: Based on local susceptibilities (choose 1)
        1. Unasyn 3 g IV every 6 hours or
        2. Imipenem 0.5 g IV every 6 hours or
        3. Ertapenem 1 g IV every 24 hours or
  7. Ulcer with extensive inflammation, deep space invasion and systemic toxicity (cover for Anaerobes, pseudomonas)
    1. Agent 1: MRSA Coverage (choose 1)
      1. Vancomycin 30 mg/kg IV every 12 hours (first-line for MRSA) or
      2. Linezolid 600 mg orally twice daily or
      3. Daptomycin 6 mg/kg IV q24 hours
    2. Agent 2: Streptococcus, Anaerobe, Pseudomonas coverage
      1. Zosyn 3.375 g IV every 6 hours or
      2. Imipenem/Cilastin (Primaxin) 500 mg IV every 6 hours or
      3. Meropenem 1 g IV every 8 hours or
      4. Metronidazole 500 mg orally every 6-8 hours AND (Ciprofloxacin or Levofloxacin or Aztreonam)
  8. Other adjunctive antibiotic options
    1. Rifampin
      1. Consider as adjunctive in Diabetic Foot Osteomyelitis
      2. Wilson (2019) JAMA Netw Open 2(11):e1916003 +PMID:31755948 [PubMed]

XI. Management: Intensive Management Indications

  1. Hospitalization Indications
    1. Moderate infection hospitalization indications
      1. Comorbid Peripheral Arterial Disease
      2. Poor glycemic control
      3. Unreliable patient for maintaining antibiotic regimen, wound care, off-loading and close-interval follow-up
    2. Severe infection or systemic infection with signs of toxicity
    3. Metabolic instability
    4. Rapidly progressive or deep infection
    5. Significant wound necrosis
    6. Gangrene
    7. Limb-critical ischemia
    8. Urgent or emergent intervention required
  2. Surgery Indications
    1. Deep abscess
    2. Bone or joint extensively involved
    3. Crepitation
    4. Significant wound necrosis
    5. Gangrene
    6. Necrotizing Fasciitis

XII. Complications: Diabetic Foot Osteomyelitis

  1. See Diabetic Foot Osteomyelitis
  2. Epidemiology
    1. Present in 20% of mild to moderate Diabetic Foot Infections
    2. Present in up to 60% of severe Diabetic Foot Infections
  3. Indications to evaluate for Osteomyelitis
    1. Foot Ulcers >2 cm in diameter
    2. Foot Ulcers >3mm deep
    3. Foot Ulcers overlying a bony prominence
    4. Chronic Diabetic Foot Ulcers refractory to healing
    5. Probe-to-Bone Test positive (or bone visible)

XIII. Prevention

  1. See Diabetic Foot Care
  2. Avoid foot injuries
  3. Daily foot care and examination to catch Foot Wounds early (cuts, Blisters)
  4. Foot exam at each clinic visit (socks and shoes off!)
    1. Assess for Diabetic Neuropathy with monofilament test (at least once yearly)
  5. Careful wound care
  6. Unload extremity of local pressure sources
    1. Examples: non-weight bearing, well-fitting shoes
    2. Keeping pressure off wound is far more important than any particular Wound Dressing choice
  7. Optimize glycemic control

XIV. References

  1. (2019) Sanford Guide, accessed on IOS 2/12/2020
  2. Hellekson (2005) Am Fam Physician 71:1429-33 [PubMed]
  3. Gemechu (2013) Am Fam Physician 88(3):177-84 [PubMed]
  4. Lipsky (2012) Clin Infect Dis 54(12): e132-73 [PubMed]

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Related Studies

Ontology: Cellulitis in diabetic foot (C0406132)

Concepts Disease or Syndrome (T047)
SnomedCT 200687002
English diabetes mellitus with complication cellulitis in foot, Cellulitis in diabetic foot (diagnosis), Cellulitis in diabetic foot, Cellulitis in diabetic foot (disorder)
Spanish celulitis en el pie diabético (trastorno), celulitis en el pie diabético
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Infection of foot associated with diabetes (C1642836)

Concepts Pathologic Function (T046)
SnomedCT 419100001
Spanish infección del pie asociada con diabetes (trastorno), infección del pie asociada con diabetes
English disorder of lower extremity foot infection associated with diabetes, Infection of foot associated with diabetes (diagnosis), Infection of foot associated with diabetes (disorder), Infection of foot associated with diabetes
Derived from the NIH UMLS (Unified Medical Language System)

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