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
      • 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


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

ARUP Lab 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®