Bacteria

Necrotizing Soft Tissue Infection

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Necrotizing Soft Tissue Infection, Necrotizing Fasciitis, Fournier's Gangrene, Fournier's Scrotal Gangrene, Necrotizing Streptococcal Fasciitis

  • Definitions
  1. Necrotizing Fasciitis
    1. Rapidly progressive, deep subcutaneous infection resulting in tissue necrosis and systemic toxicity
  2. Fournier's Gangrene
    1. Massive infection and swelling of Scrotum and penis
    2. Extends into perineum or abdominal wall, and legs
    3. Seen in Alcoholic Liver Disease or Cirrhosis, Diabetes Mellitus, IV Drug Abuse
  • Precautions
  1. Necrotizing Fasciitis is a life threatening infection with an insidious, occult presentation
  2. Do not ignore pain out of proportion, Sinus Tachycardia or unexplained fever
  3. Do not delay surgical exploration when Necrotizing Fasciitis is suspected
  4. Physical exam, labs and imaging are unreliable alone at excluding Necrotizing Fasciitis
  • Pathophysiology
  1. Typically starts with break in skin (e.g. Trauma or recent surgery)
  2. Infection spreads between fascia and subcutaneous tissue
  3. Fibrous bands prevent infectious spread
    1. Present in head and distal extremities
    2. Lacking in trunk and proximal extremities
  • Risk factors
  1. Age over 50 years
  2. Malnutrition
    1. Hypoalbuminemia
    2. Alcoholism
    3. Cirrhosis (esp. Vibrio vulnificans from seafood)
      1. Liver disease is associated with higher mortality
  3. Immunocompromised state (esp. Neutropenia)
    1. Cancer
    2. Corticosteroid use
    3. HIV Infection
  4. Poor vascular supply
    1. Cardiovascular disease
    2. Peripheral Vascular Disease
    3. Diabetes Mellitus
      1. Most common comorbidity (present in 45% of cases)
      2. Higher amputation risk
      3. Diabetic Neuropathy may result in less recognition of pain
  5. Skin Trauma within last 90 days
    1. Burn Injury
    2. Trauma
    3. Intravenous Drug Abuse
    4. Recent surgery
    5. Alcohol Abuse
  6. Miscellaneous risk factors
    1. Obesity
  7. Break in Gastrointestinal or Genitourinary mucosa
    1. Colon Cancer
    2. Diverticula
    3. Hemorrhoids or Anal Fissure
    4. Urethral tear
    5. Cirrhosis
  • Findings
  • Symptoms and Signs progression (in order of occurrence)
  1. Pain out of proportion to physical findings (79%)
  2. Unexplained fever (40%)
  3. Tachycardia (60%)
  4. Swelling (80% of cases)
  5. Foul odor
  6. Subcutaneous air with crepitation (pathognomonic, but late finding)
  7. Rapid progression
  8. Brawny Edema and tenderness
  9. Erythema with indistinct margins
  10. Dark red induration
  11. "Dish water" wound drainage
  12. Involved area may parodoxically be without sensation
  13. Bullae filled with blue or purple fluid
  14. Skin friable, bluish, maroon, or black
  15. Extensive thrombosis of dermal blood vessels
  16. Extension to deep fascia leads to brown-gray appearance
  17. Rapid spread along fascial planes, veins and lymph
  18. Toxicity, shock, and multi-organ failure
  • Signs
  • Distribution
  1. Extremities (53%)
  2. Perineum or buttocks (20%, especially in Diabetes Mellitus, Alcoholism)
  3. Trunk (18%)
  4. Head and neck (9%)
  5. References
    1. Bosshardt (1996) Arch Surg 131:846-52 [PubMed]
  • Exam
  1. Mark the erythematous border of infection
    1. Mark the time of each consecutive margin re-evaluation
  • Types
  1. Polymicrobial (Type 1) - Mixed aerobic and Anaerobic Bacteria
    1. Break in Gastrointestinal or Genitourinary mucosa or on trunk and extremities
    2. Includes Fournier's Gangrene
    3. Comorbid conditions associated with mixed infection
      1. Diabetes Mellitus
      2. Peripheral Vascular Disease
      3. Immunocompromised state
    4. Typically a combination of anaerobic and aerobic Bacteria
      1. Anaerobic Bacteria include Bacteroides, Clostridium, peptostreptococcus
      2. Aerobic Bacteria include E. coli, Klebsiella, Enterobacter and Proteus
  2. Monomicrobial (Type 2)
    1. Causes
      1. Group A Streptococcus (Streptococcus Pyogenes)
      2. Staphylococcus aureus
      3. Vibrio vulnificus
    2. Begins deep at non-penetrating minor Trauma in typically healthy patients
      1. Risk Factors include IV Drug Abuse and skin popping
      2. May also be associated with Toxic Shock Syndrome
      3. Contusion seeded by transient bacteremia
    3. Findings
      1. Gas production only if mixed infection
      2. Severe toxicity, renal Impairment may precede shock
      3. Myositis in 20-40% cases
      4. Creatine Phosphokinase (CPK) is markedly elevated
      5. Mortality: 20-50% despite Penicillin
  1. Group A Streptococcus (Streptococcus Pyogenes)
  2. Staphylococcus aureus
  3. Clostridium perfringens
    1. Hyperbaric Oxygen treatment may help in Gas Gangrene
  4. Vibrio haemlyticus or Vibrio vulnificus (sea water exposure, seafood ingestion esp. in Cirrhosis)
  5. Aeromonas (fresh water exposure)
  6. Plesiomonas (fresh water exposure)
  7. Superinfection of varicella in children
  8. Omphalitis (Umbilical Cord stump infection) in newborns
  • Diagnosis
  • Findings Suggestive of Necrotizing Fasciitis
  1. Altered Mental Status
  2. Soft tissue erythema, edema and severe pain (70-80% of cases)
    1. Pain out of proportion to the exam
    2. Tenderness outside the erythematous borders
  3. Vessicles or Bullae (25%)
    1. Bullae become violaceous after 4-5 days
    2. Skin then becomes necrotic
    3. Hemorrhagic bullae are nearly pathognomonic for Necrotizing Fasciitis (esp. Vibrio vulnificus)
  4. Fever (40%)
    1. Temperature over 99.5 F (37.5 C)
  5. Tachycardia
    1. Unresponsive to Intravenous FluidResuscitation and antipyretics
  6. Hypotension (21%)
    1. Systolic Blood Pressure <90 mmHg
  7. Tissue Crepitation (20%)
    1. In Fournier's Gangrene, may not be readily evident (e.g. inguinal region or buttocks)
  • Diagnosis
  1. Definitive diagnosis
    1. Deep tissue biopsy with culture and Gram Stain (performed during surgical source control as below)
  2. Finger Test
    1. Indicated in remote medical care in resource limited regions (lacking imaging, surgical Consultation, delayed transfer)
    2. Local Anesthetic injected within suspected infection region (inject into deep space)
    3. Make 2 cm incision
    4. Expose tissue down to deep fascia
    5. Findings consistent with Necrotizing Fasciitis
      1. Dishwater-like fluid appears from wound site, but no significant bleeding
      2. Gloved finger inserted into deep fascia offers little resistance
  • Labs
  1. LRINEC Score
    1. See Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC Score)
    2. High False Positive and False Negative Rate (misses up to 50% of cases)
  2. Complete Blood Count
    1. White Blood Cell Count over 15,000/mm3 (esp. if >25,000/mm3)
    2. Hemoglobin less than 11 g/dl
    3. Platelet Count <150,000 per mm3
  3. Serum Electrolytes
    1. Serum Sodium under 135 meq/L (SIADH related)
    2. Blood Urea Nitrogen 15 mg/dl
    3. Serum Calcium under 8.4 mg/dl
    4. Serum Creatinine >1.6 mg/dl
  4. Coagulation Studies
    1. Prothrombin Time (PT) prolonged
    2. Partial Thromboplastin Time (aPTT) prolonged
  5. Other markers
    1. C-Reactive Protein >150 mg/L
    2. Arterial or venous pH < 7.35
  • Imaging
  1. Background
    1. Liquefaction necrosis and gas formation lead to many of the findings on imaging
  2. XRay
    1. Test Sensitivity: 25-50% for subcutaneous gas
    2. Test Specificity: 94%
    3. Gas along fascial planes is pathognomonic for Necrotizing Fasciitis (but a late finding)
    4. Negative xray does NOT exclude Necrotizing Fasciitis
  3. Ultrasound
    1. Consider in children, or in Ultrasound-guided fluid aspiration
    2. Fascial planes are thickened and distorted with fluid and subcutaneous edema
      1. Fluid at fascial layer 1 mm with Test Sensitivity 87%, Test Specificity 50%
      2. Fluid at fascial layer 5 mm with Test Specificity 98%
    3. Limited visualization if soft-tissue gas is present
      1. Gas-related shadowing appears as scattered clouds within tissue
  4. CT
    1. Soft tissue gas formation in subcutaneous and deep tissues
    2. Deep fascia contains fluid tracking around its planes (inconsistent)
    3. Superficial and deep fascial layers (as well as subcutaneous fat) with thickening and contrast enhancement
    4. Abscess may variably be present
    5. Reactive Lymphadenopathy
    6. Identitifies other complications (e.g. vascular rupture) as well as conditions in differential diagnosis
    7. CT is a first-line study in fourniers gangrene
      1. Contrast is not required for fourniers diagnosis, but contrast allows for differential diagnosis evaluation
  5. MRI
    1. Preferred imaging if no delay, and patient stable enough to withstand the lengthy study in the radiology department
    2. Efficacy
      1. Test Sensitivity: 100%
      2. Test Specificity: 86%
    3. Findings
      1. Fascial fluid (abnormally increased signal on T2-weighted images)
      2. Gas bubbles (variably present, signal voids on T1 and T2-weighted images)
      3. Reticular increased signal at subcutaneous tissues (similar to Cellulitis) as well as deep fascia involvement
        1. Deep intermuscular fascia involvement
        2. Fascial thickening (>3mm)
        3. Thickened fascia completely lacks signal enhancement post-Gadolinium
      4. Necrotic tissue is over-estimated as normal tissue may have a similar appearace on MRI
      5. Gadolinium is optional for diagnosis but assists in identifying abscesses, joint effusions
  6. References
    1. Malghem (2013) Joint Bone Spine 80(2): 146-54 [PubMed]
    2. Fugitt (2004) Radiographics 24(5): 1472-6 +PMID:15371620 [PubMed]
      1. https://pubs.rsna.org/doi/pdf/10.1148/rg.245035169
  • Management
  • Surgical exploration to fascia and muscle
  1. Early exploration and surgical debridement within 12 hours is critical (delay risks higher mortality)
  2. Observe for
    1. Necrotizing Fasciitis
    2. Myositis
    3. Gangrene
  3. Technique
    1. Visualize deep structures
    2. Remove necrotic materials
    3. Reduce compartment pressure
    4. Send material for Gram Stain and Culture
  • Management
  • Empiric
  1. Expect Cellulitis to improve with antibiotics
    1. Necrotizing Fasciitis will worsen with antibiotic management alone
    2. Monitor closely for signs of deep space infection in unclear cases
  2. Combination Regimen (3 drugs plus MRSA coverage)
    1. Anaerobe and Gram Positive coverage (and inhibits ribosomal production of toxins)
      1. Clindamycin 600 to 900 mg IV every 8 hours (40 mg/kg/day divided every 8 hours in children)
    2. Gram Positive coverage
      1. Ampicillin-sulbactam (Unasyn) 1.5 to 3 g IV every 6-8 hours OR
      2. Piperacillin-tazobactam 3.375 IV q6-8 hours
    3. Gram Negative coverage
      1. Ciprofloxacin 400 mg IV every 12 hours
  3. Combination Regimen (2 drugs plus MRSA coverage)
    1. Cefotaxime 2 grams IV every 6 hours AND
    2. Anaerobic coverage
      1. Metronidazole 50 mg IV every 6 hours OR
      2. Clindamycin 600 mg IV every 8 hours (typically preferred)
  4. Single agent regimens (choose one plus MRSA coverage and often Clindamycin is added)
    1. Imipenem-Cilastin 1 g IV every 6-8 hours
    2. Meropenem 1 g IV every 8 hours
    3. Ertapenem 1 g IV every 24 hours
  5. MRSA Coverage (use with above regimens)
    1. Vancomycin 15 mg/kg IV every 12 hours
    2. Linezolid 600 mg IV every 12 hours
  6. Other antibiotics
    1. Add Doxycycline if hemorrhagic bullae are seen (cover for Vibrio vulnificus)
  7. Other measures
    1. Maximize nutritional status
  1. Indications
    1. Household contact exposure from onset to 48 hours from antibiotic start
  2. Treatment options (choose one)
    1. Penicillin G Benzathine
      1. Weight <60 pounds (<27 kg): 600,000 units IM for 1 dose or
      2. Weight >60 pounds (<>7 kg): 1,200,000 units IM for 1 dose
    2. Rifampin 5 mg/kg/day (up to 300 mg maximum) orally twice daily for 4 days
    3. Clindamycin 20 mg/kg (up to 300 mg maximum) orally three times daily for 10 days
    4. Azithromycin (Zithromax) 12 mg/kg (up to 500 mg) orally daily for 5 days
  3. References
    1. Sablier (2010) Lancet 375(9719): 1052 [PubMed]
  • Prognosis
  1. Mortality: 25-35% (up to 70% in those who develop Sepsis, 100% with delayed diagnosis, management)
  2. Truncal involvement mortality approaches 100%
  3. Hypotension is a strong predictor of multiorgan failure and death
  • References
  1. Binder (2019) Crit Dec Emerg Med 33(9): 28-9
  2. Goldberg (2015) Crit Dec Emerg Med 29(3): 9-19
  3. Mason, Herbert and Swadron in Herbert (2019) EM:Rap C3 3(10): 1-12
  4. Jhun and Raam in Herbert (2016) EM:Rap 16(8): 9-10
  5. Inaba, Swadron, Long and Gottlieb in Herbert (2020) EM:Rap 20(10):10-11
  6. Inaba, Swadron, Long and Gottlieb in Herbert (2020) EM:Rap 20(11):11-2
  7. Elliott (2000) Am J Surg 179:361-6 [PubMed]
  8. Headley (2003) Am Fam Physician 68(2):323-8 [PubMed]
  9. Ramakrishnan (2015) Am Fam Physician 92(6): 474-83 [PubMed]
  10. Usatine (2010) Am Fam Physician 82(7): 773-80 [PubMed]
  11. Wall (2000) J Am Coll Surg 191:227-31 [PubMed]