Necrotizing Soft Tissue Infection

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

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II. 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

III. Epidemiology

  1. Necrotizing Fasciitis Incidence: 0.4 per 100,000 persons in U.S.
    1. Incidence as high in some world regions as 1 in 100,000

IV. 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. Patients with severe Neuropathy (e.g. Diabetes Mellitus) may have occult presentations with fever (perform a careful skin exam)
  4. Do not delay surgical exploration when Necrotizing Fasciitis is suspected
  5. Physical exam, labs and imaging are unreliable alone in excluding Necrotizing Fasciitis

V. Pathophysiology

  1. Typically starts with break in skin (e.g. Trauma or recent surgery)
    1. Initial Skin Injury is often unrecognized by the patient (often a minor skin break)
  2. Infection spreads between fascia and subcutaneous tissue
    1. Skin tissue is typically compromised at baseline allowing for rapid spread (see risk factors above)
  3. Fibrous bands typically prevent infectious spread
    1. Fibrous bands are present in head and distal extremities
    2. Fibrous bands are lacking in the trunk and proximal extremities

VI. 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

VII. 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 (hemorrhagic Bullae)
  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

VIII. 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]

IX. Exam

  1. Assess systemic toxicity
    1. Toxic appearance
    2. SIRS Criteria (fever, Tachycardia)
    3. Hypotension
  2. Serial exams are critical
    1. Initial symptoms (Fever Without Source, pain out of proportion) may have few localized physical findings
  3. Skin Exam
    1. Perform a complete skin examination with clothes removed
    2. Careful exam for wounds, ulcerations, injection sites
    3. Mark the erythematous border of infection (time of each consecutive margin re-evaluation)
      1. Mark poorly demarcated margins
      2. Identify islands of erythema with skipped areas of normal skin (seen with deeper soft tissue spread)

X. Types

  1. See Clostridial Myonecrosis (Gas Gangrene)
  2. Polymicrobial (Type 1) - Mixed aerobic and Anaerobic Bacteria
    1. Break in Gastrointestinal or Genitourinary mucosa or on trunk and extremities
    2. Includes regional syndromes
      1. Necrotizing Infection of the Head and Neck (e.g. Fusobacterium Pharyngitis, Ludwig's Angina)
      2. Fournier's Gangrene (Gram Negative Bacteria and Anaerobes)
    3. Comorbid conditions associated with mixed infection
      1. Elderly patients
      2. Diabetes Mellitus
      3. Peripheral Vascular Disease
      4. 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
    5. Findings
      1. Gas in tissue (also seen in clostridal myonecrosis)
  3. Monomicrobial (Type 2)
    1. Causes
      1. Group A Streptococcus (Streptococcus Pyogenes) or other Beta-hemolytic Streptococcus
      2. Less common causes
        1. Staphylococcus aureus
        2. Vibrio vulnificus (see Vibrio Cellulitis, saltwater Gram Negative Rod)
        3. Aeromonas (fresh water Gram Negative Rod)
    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. Soft tissue Contusion seeded by transient bacteremia (often from nasopharyngeal source)
    3. Findings
      1. Gas production only if mixed infection (gas is typically absent)
      2. Soft tissue swelling is prominent
      3. Severe toxicity, renal Impairment may precede shock
      4. Associated Diarrhea, Anorexia, fever with Group A Streptococcus
      5. Necrotizing Myositis in 20-40% cases
      6. Creatine Phosphokinase (CPK) is markedly elevated
      7. Mortality: 20-50% despite Penicillin

XI. Causes: Bacteria

  1. Group A Streptococcus (Streptococcus Pyogenes)
  2. Staphylococcus aureus
  3. Clostridium perfringens
    1. See Clostridial Myonecrosis (Gas Gangrene)
    2. 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

XII. Diagnosis: Findings Suggestive of Necrotizing Fasciitis

  1. Altered Mental Status
  2. Soft tissue edema (70-80% of cases)
  3. Soft tissue erythema (72%)
  4. Severe Pain out of proportion to the exam (72%)
    1. Tenderness outside the erythematous borders
  5. 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)
  6. Fever (40-60%)
    1. Temperature over 99.5 F (37.5 C)
  7. Tachycardia
    1. Unresponsive to Intravenous FluidResuscitation and antipyretics
  8. Hypotension (21%)
    1. Systolic Blood Pressure <90 mmHg
  9. Tissue Crepitation (20%)
    1. In Fournier's Gangrene, may not be readily evident (e.g. inguinal region or buttocks)

XIII. 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

XIV. 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 to 60% of cases)
      1. Neeki (2017) West J Emerg Med 18(4): 684-9 [PubMed]
  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

XV. Imaging

  1. Background
    1. Liquefaction necrosis and gas formation lead to many of the findings on imaging
    2. Necrotizing Fasciitis is a surgical diagnosis, and imaging should not delay definitive management
  2. XRay
    1. Negative xray does NOT exclude Necrotizing Fasciitis
    2. Subcutaneous gas finding efficacy in Necrotizing Fasciitis diagnosis
      1. Gas along fascial planes is pathognomonic for Necrotizing Fasciitis (but a late finding)
      2. Test Sensitivity: 25-50%
      3. Test Specificity: 94%
  3. Ultrasound
    1. Consider in children, or in Ultrasound-guided fluid aspiration
    2. General findings of Cellulitis may be seen (subcutaneous cobblestoning)
    3. Fascial planes are thickened and distorted with fluid (may be swirling) 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%
    4. Limited visualization if soft-tissue gas is present
      1. Gas-related shadowing appears as scattered clouds within tissue ("dirty shadowing")
      2. Air bubbling in subcutaneous tissue ("champagne sign")
  4. CT Imaging
    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
    8. Efficacy (CT does not exclude Necrotizing Fasciitis)
      1. Test Sensitivity: 89%
      2. Test Specificity: 93%
  5. MRI
    1. Preferred imaging if no delay, and patient stable enough to withstand the lengthy study in the radiology department
      1. In most emergency departments, MRI is not practical or safe to perform in these clinically Unstable Patients
      2. CT imaging (as above) is often used emergently instead of MRI
    2. Efficacy
      1. Test Sensitivity: 93 to 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

XVI. Differential Diagnosis

  1. Superficial Skin Infections (no significant systemic signs or Necrotizing Fasciitis critieria)
    1. See Skin Infection (Pyoderma)
    2. Cellulitis
    3. Erysipelas
    4. Skin Abscess
  2. Clostridial Myonecrosis (Gas Gangrene)
    1. Clostridium perfringens (Traumatic source)
    2. Clositridium septicum (spontaneous source without skin break)
    3. Clostridium sordellii (gynecologic source)
  3. Pyomyositis (skeletal Muscle abscess)
  4. Toxic Shock Syndrome
  5. Necrotizing Insect Bite (e.g. Brown Recluse Spider)
  6. Septic Superficial Thrombophlebitis
  7. Anaphylaxis

XVII. 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
      1. Serial Debridement surgeries are common
      2. Amputation may be required to prevent further spread of infection
    3. Reduce Compartment Pressure
    4. Send material for Gram Stain and Culture

XVIII. Management: Empiric

  1. Background
    1. Clindamycin is added to most regimens for toxin suppression (inhibits ribosomal production of toxins)
    2. Expect Cellulitis to improve with Antibiotics
      1. Necrotizing Fasciitis will worsen with Antibiotic management alone (requires surgical management)
      2. Monitor closely for signs of deep space infection in unclear cases
  2. MRSA Coverage (use with below regimens)
    1. Vancomycin 15 mg/kg IV every 12 hours OR
    2. Linezolid 600 mg IV every 12 hours
  3. 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. Piperacillin-tazobactam (Zosyn) 3.375 IV q6-8 hours (preferred) OR
      2. Ampicillin-sulbactam (Unasyn) 1.5 to 3 g IV every 6-8 hours
    3. Gram Negative coverage (typically zosyn is sufficient without adding this additional coverage)
      1. Ciprofloxacin 400 mg IV every 12 hours
  4. 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)
  5. 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
  6. Other Antibiotics
    1. Add Doxycycline if hemorrhagic bullae are seen (cover for Vibrio vulnificus)
  7. Other measures
    1. Maximize nutritional status
    2. Hyperbaric oxygen is unlikely to benefit most Necrotizing Fasciitis
      1. However, may be useful Clostridial Myonecrosis (Gas Gangrene) and other select cases
      2. Levett (2015) Cochrane Database Syst Rev 1(1): CD007937 [PubMed]
    3. Poly-specific IV Immune globulin (IVIG)
      1. Toxin-specific neutralizing Antibody indicated in Type 2 Necrotizing Fasciitis (esp. Group A Streptococcus)
      2. Norrby-Teglund (2005) Scand J Infect Dis 37(3): 166-72 [PubMed]

XIX. Management: Post-exposure Prophylaxis

  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]

XX. Complications

  1. Very high mortality (see below)
  2. Complex wounds, Chronic Pain and debility from extensive Debridement
  3. Intensive Care related complications (e.g. Ventilator Associated Pneumonia, catheter associated infections)
  4. Toxic Shock Syndrome
  5. Acute Kidney Injury
  6. Cardiomyopathy (associated with Toxic Shock Syndrome)
  7. Severe Anemia (Bacterial hemolysin related)

XXI. 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

XXII. 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. Khidir and Eyre (2021) Crit Dec Emerg Med 34(10): 12-3
  8. Riekena, Naganathan and Mehkri (2022) Crit Dec Emerg Med 36(6): 4-11
  9. Elliott (2000) Am J Surg 179:361-6 [PubMed]
  10. Headley (2003) Am Fam Physician 68(2):323-8 [PubMed]
  11. Ramakrishnan (2015) Am Fam Physician 92(6): 474-83 [PubMed]
  12. Stevens (2014) Clin INfect Dis 59(2): 147-59 +PMID:24947530 [PubMed]
  13. Stevens (2017) N Engl J Med 377(23):2253-65 +PMID:29211672 [PubMed]
  14. Usatine (2010) Am Fam Physician 82(7): 773-80 [PubMed]
  15. Wall (2000) J Am Coll Surg 191:227-31 [PubMed]

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