Necrotizing Soft Tissue Infections - Complicated Skin Infections

Aggressive, necrotizing soft tissue infections can cause extensive local tissue damage as well as systemic toxicity. These infections require prompt recognition to prevent severe morbidity and mortality. Laboratory testing includes gram stain of aspirates or tissue biopsies for simple infections; complicated infections may require CBC, culture, and surgical exploration of the site.


Indications for Testing

Redness, warmth, tenderness, crepitus, and induration or purulent drainage indicating infection in underlying structures, including skin, dermis, muscle, and bone

Laboratory Testing

  • Simple infections – abscesses, furuncles, carbuncles
    • Culture
      • Tissue
      • Wound
    • Gram stain of aspirates or tissue biopsies – may not be as helpful as culture, depending on organism involved and quality of specimen
  • Complicated infections – fever, tachycardia, immunocompromised state
    • CBC
    • Culture
      • Tissue
      • Wound
      • Blood – infrequently positive
    • C-reactive protein (CRP)
    • Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score
      • Use to differentiate cellulitis from more serious infection and need for surgical referral
      • ≥6 points has positive predictive value of 92% and negative predictive value of 96% for diagnosis of necrotizing fasciitis
      • Laboratory Risk Indicator for Necrotizing Fasciitis
        Variable, Units Scorea

        C-reactive protein, mg/L





        Total white cell count, per mm3







        Hemoglobin, g/dL







        Sodium, mmol/L





        Creatinine, µmol/L





        Glucose, mmol/L





        aMaximum score is 13. A score of ≥6 should raise the suspicion of necrotizing fasciitis. A score of ≥8 is strongly predictive of this disease.

        Source: Wong, 2004

      • If above studies do not confirm necrotizing fasciitis, surgical exploration of the site may confirm the disease

Imaging Studies

  • X-ray – subcutaneous air in tissue noted in about 25% of patients with complicated infections
    • May reveal foreign body in infected wounds
  • Ultrasound (US)/computed tomography (CT)/magnetic resonance imaging (MRI)
    • Choose imaging study based on suspected location of infection and usefulness for site infected
    • Imaging frequently used for localized drainage of identified site

Differential Diagnosis

  • Local infections (furuncles, cellulitis, abscesses, etc.)
  • Insect and spider bites
  • Fungal (Candida) septicemia
  • Allergic reaction
  • Crystalline arthritis
  • Tenosynovitis (associated with inflammatory arthropathy)



  • Incidence – 500-1,500 cases per year in the U.S. (Anaya, 2007)
  • Age – increased frequency in older patients
  • Sex – M:F, equal
    • Exception in Vibrio vulnificus, M>F
  • Transmission – skin entry via break in dermis


  • Type I – polymicrobial infection with aerobes, anaerobes, and facultative bacterial species
  • Type II – monomicrobial, generally, with gram-positive streptococci or staphylococci, especially
    • Group A beta-hemolytic streptococci, or
    • Methicillin-resistant Staphylococcus aureus (MRSA)
  • Type III – infection with gram-negative rods, especially Clostridium perfringens
  • Other generally recognized types outside of this Type I-III classification system are caused by V. vulnificus or fungal infection
  • Additional subclassifications formerly known by other terms are now described using general term “necrotizing soft tissue infections” (NSTIs)
    • Necrotizing fasciitis – necrotizing infection of the deep fascia
    • Fournier’s gangrene – necrotizing soft tissue infection of the perineum
    • Clostridial myonecrosis/gangrene/gas gangrene – necrotizing infection of muscle due to C. perfringens or related gas-producing organisms


  • Monomicrobial infection – one third of infections
  • Polymicrobial infection more common – about two thirds of infections
  • Most common organisms
    • Staphylococcus spp (including MRSA)
    • Streptococcus spp
  • Other common organisms
    • Enterococci
    • Pseudomonas aeruginosa
    • Enterobacteriaceae
    • Bacteroides spp
    • Proteus spp
    • Clostridium spp

Risk Factors

  • Approximately 30% of NSTIs occur in healthy individuals with no risk factors (Mishra, 2013)
  • Risk factors include (Anaya, 2007; Mishra, 2013)
    • Diabetes mellitus
    • Intravenous drug use
    • Alcohol abuse
    • Cancer or other immunocompromised state
    • Peripheral vascular disease
    • Obesity or malnutrition
    • Trauma
    • Postoperative infection
    • Burns

Clinical Presentation

  • General symptoms
    • Cutaneous – erythema, tense edema, vesicles or bullae, necrosis ulcers, crepitus, gray or discolored wound drainage, pain extending past margin of skin infection
    • Constitutional – fever, diaphoresis, delirium, tachycardia, tachypnea
    • Most common locations – extremities (50-55%), perineum/buttocks (20%), trunk (18-20%), head and neck (8-10%)
  • Clinical markers that may help differentiate necrotizing infection from localized infection include
    • Pain disproportionate to appearance of infection
    • Crepitus
    • High fever
    • Rapidly spreading erythema
    • Organisms and Clinical Scenarios/Presentations
      Organism Common Clinical Scenario Common Comorbid Conditions Clinical Presentation Prevalence

      Streptococcus species (Group A)

      Skin abrasion, trauma, recent skin infection (herpes zoster, varicella-zoster, herpes simplex), human bite, intravenous/subcutaneous drug abuse

      Diabetes, cancer, alcohol abuse, stasis dermatitis, eczema (commonly occur in individuals with no risk factors)

      Intense erythema, edema and pain, lymphadenopathy, hemorrhagic and necrotic bullae, muscle myositis, erysipelas, impetigo, type II necrotizing fasciitis

      One of the 2 most common monomicrobial infectious agents

      Peptostreptococcus and gram-negative organisms

      Colorectal or genitourinary disease; orofacial surgery, dental work

      Older patients

      Scrotal edema and perineal gangrene (Fournier gangrene), submandibular space (Ludwig angina)

      Usually found in association with other organisms

      Staphylococcus aureus

      Skin trauma, recent hospitalization or surgery, intravenous/subcutaneous drug abuse

      Obesity, diabetes, immunocompromised state, eczema, rheumatologic disease

      Furuncles, local abscesses, diffuse macular erythroderma, pyomyositis, toxic shock syndrome, staphylococcal scalded skin syndrome

      One of the most common agents of soft tissue skin infections

      Polymicrobial (eg, beta-hemolytic streptococci with S. aureus [including MRSA], S. epidermidis, or gram-negative bacteria such as E. coli, Proteus mirabilis, Klebsiella pneumoniae)

      Diabetic foot ulcer, recent surgery with purulent wound

      Diabetes, immunocompromised state, vascular disease (particularly lower extremity disease)

      Moist gangrene with a foul odor, suppurative-necrotic ulcer surrounded by concentric zones of red cellulitis (Meleney gangrene), deeper abscess, type I necrotizing fasciitis

      Most common presentation for necrotizing infections (>50% )

      Pseudomonas species

      Bacteremia, moist skin infection, severe burn, recent hospitalization

      Immunocompromised state, diabetes

      Hemorrhagic and necrotic bullae


      Vibrio vulnificus

      Exposure to raw or undercooked seafood or exposure to seawater

      Chronic liver disease, immunocompromised state

      Hemorrhagic and necrotic bullae, ecchymoses

      Unusual in immunocompetent patients

      Clostridium perfringens

      Severe trauma with wound contamination, recent surgery, intravenous drug abuse


      Pale skin, edema, hemorrhagic and necrotic bullae, foul-smelling discharge, gas formation

      Usually found in association with local tissue injury

      Pasteurella multocida

      Cat or dog bite


      Erythema, edema, serosanguineous discharge, lymphadenitis, tenosynovitis

      Typically associated with animal bite

      Aspergillus, Mucor, Rhizopus species

      Traumatic wounds or burns

      Immunocompromised state

      Erythema, severe pain, hemorrhagic bullae

      Rare in immunocompetent patients

      Aeromonas hydrophila

      Exposure to fresh water, skin abrasion

      Usually none; occasionally immunocompromised state

      Erythema, bullae, necrosis, possible gas formation

      Unusual in immunocompetent patients

      MRSA, methicillin-resistant Staphylococcus aureus; n/a, not available


  • Vibrio – do not eat raw seafood; avoid exposing open wounds to seawater
  • Pasteurella – begin prophylaxis at time of bite for serious bite wounds

ARUP Laboratory Tests

Help differentiate aggressive (systemic) infection from local infection

May not be elevated in spite of aggressive disease

Identify bacteria in tissues

Anaerobe culture is recommended for body fluids, tissue, and deep wound/surgical cultures; refer to anaerobe culture and gram stain

Anaerobe culture is NOT included with this order

Important informationLimited to the University of Utah Health Sciences Center only

Identify bacteria in wounds

Anaerobe culture is recommended for body fluids, tissue, and deep wound/surgical cultures; refer to anaerobe culture and gram stain

Anaerobe culture is NOT included with this order

Detect presence of bacteria in blood

Important informationTesting is limited to the University of Utah Health Sciences Center only

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

Component of Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score

Component of LRINEC score

Related Tests

ARUP recommends contacting your local or state health department in suspected botulism cases

If local and state officials are not available, the Centers for Disease Control and Prevention (CDC) can be contacted

Clostridium botulinum culture

Medical Experts



Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories


Mark A. Fisher, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Bacteriology, Special Microbiology, and Antimicrobial Susceptibility Testing, ARUP Laboratories


Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®