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Necrotizing Soft Tissue Infection

(Necrotizing Cellulitis; Necrotizing Fasciitis; Necrotizing Subcutaneous Infection)


Wingfield E. Rehmus

, MD, MPH, University of British Columbia

Last full review/revision Feb 2021| Content last modified Feb 2021
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Necrotizing soft tissue infection is typically caused by a mixture of aerobic and anaerobic organisms that cause necrosis of subcutaneous tissue, usually including the fascia. This infection most commonly affects the extremities and perineum. Affected tissues become red, hot, and swollen, resembling severe cellulitis, and pain develops out of proportion to clinical findings. During surgical exploration, there is a gray exudate, friable superficial fascia, and absence of pus. Without timely treatment, the area becomes gangrenous. Patients are acutely ill. Diagnosis is by history and examination and is supported by evidence of overwhelming infection. Treatment involves antibiotics and surgical debridement. Prognosis is poor without early, aggressive treatment.

Etiology of Necrotizing Soft Tissue Infection

There are three subtypes of necrotizing soft tissue infection (NSTI): 

  • Type I

  • Type II

  • Type III

Type I NSTI, typically involving the torso and perineum, results from a polymicrobial infection usually including group A streptococci (eg, Streptococcus pyogenes) and a mixture of aerobic and anaerobic bacteria (eg, Bacteroides species). These organisms typically extend to subcutaneous tissue from a contiguous ulcer or infection, or after trauma. Streptococci can arrive from a remote site of infection via the bloodstream. Perineal involvement (also called Fournier gangrene) is usually a complication of recent surgery, perirectal abscess, periurethral gland infection, or retroperitoneal infection resulting from perforated abdominal viscera. Patients with diabetes are at particular risk of type I NSTI. Type I infections often produce gas in the soft tissue, making its manifestation similar to that of gas gangrene (clostridial myonecrosis), which is a monomicrobial infection (1).

Manifestations of Necrotizing Soft Tissue Infection (NSTI)

Type II NSTI is monomicrobial and is most commonly caused by group A beta-hemolytic streptococci; Staphylococcus aureus is the second most common pathogen. Patients tend to be younger with few documented health problems but may have a history of IV drug use, trauma, or recent surgery. The infection has the potential for rapid local spread and systemic complications such as toxic shock.

Type III NSTI is usually associated with aquatic injuries sustained in warmer coastal areas. Vibrio vulnificus is the usual pathogen. Type III infections share clinical similarities to type II infections and may spread rapidly.

Etiology reference

  • 1. Stevens DL, Bryant AE: Necrotizing soft-tissue infections. N Engl J Med 377(23):2253–2265, 2017. doi: 10.1056/NEJMra1600673

Pathophysiology of Necrotizing Soft Tissue Infection

Necrotizing soft tissue infection causes tissue ischemia by widespread occlusion of small subcutaneous vessels. Vessel occlusion results in skin infarction and necrosis, which facilitates the growth of obligate anaerobes (eg, Bacteroides) while promoting anaerobic metabolism by facultative organisms (eg, Escherichia coli), resulting in gangrene. Anaerobic metabolism produces hydrogen and nitrogen, relatively insoluble gases that may accumulate in subcutaneous tissues.

Symptoms and Signs of Necrotizing Soft Tissue Infection

The primary symptom of necrotizing soft tissue infection is intense pain. In patients with normal sensation, pain out of proportion to clinical findings may be an early clue. However, in areas denervated by peripheral neuropathy, pain may be minimal or absent. Affected tissue is red, hot, and swollen and rapidly becomes discolored. Bullae, crepitus (resulting from soft-tissue gas), and gangrene may develop. Subcutaneous tissues (including adjacent fascia) necrose, with widespread undermining of surrounding tissue. Muscles may be spared initially but can be involved as the disorder progresses. Patients are acutely ill, with high fever, tachycardia, altered mental status ranging from confusion to obtundation, and hypotension. Patients may be bacteremic or septic and may require aggressive hemodynamic support. Streptococcal toxic shock syndrome may develop.

Diagnosis of Necrotizing Soft Tissue Infection

  • Clinical examination

  • Blood and wound cultures

Diagnosis of NSTI, made by history and examination, is supported by leukocytosis, elevated C-reactive protein, soft-tissue gas on x-ray, positive blood cultures, and deteriorating metabolic and hemodynamic status.

CT and MRI can be used to delineate disease, but treatment should not be delayed while awaiting imaging results.

During surgical exploration, there is a gray exudate, friable superficial fascia, and absence of pus.

Prognosis for Necrotizing Soft Tissue Infection

Mortality rate is about 30% for all causes. Old age, underlying medical problems, delayed diagnosis and therapy, and insufficient surgical debridement worsen prognosis.

Treatment of Necrotizing Soft Tissue Infection

  • Surgical debridement

  • Antibiotics

  • Amputation if necessary

Treatment of early necrotizing soft tissue infection is primarily surgical, which should not be delayed by diagnostic studies.

Evidence of bullae, ecchymosis, fluctuance, crepitus, and systemic spread of infection requires immediate surgical exploration and debridement. The initial incision should be extended until an instrument or finger can no longer separate the skin and subcutaneous tissue from the deep fascia. The most common error is insufficient surgical intervention; repeat operation every 1 to 2 days, with further incision and debridement as needed, should be carried out routinely. Negative-pressure wound therapy (NPWT, also called vacuum-assisted closure, or VAC), which applies suction to the wound, has been used as an adjunct for care between debridements.

Amputation of an extremity may be necessary.

IV antibiotics are adjuncts, usually including 2 or more drugs. An empiric regimen should include drugs effective against aerobic and anaerobic organisms. Current recommendations from the Infectious Diseases Society of America (IDSA) suggest vancomycin, linezolid, or daptomycin combined with piperacillin/tazobactam, a carbapenem, ceftriaxone plus metronidazole, or a fluoroquinolone plus metronidazole. Antibiotic coverage should be narrowed based on blood and tissue culture results once they become available. (See the IDSA's practice guidelines for the diagnosis and management of skin and soft-tissue infections.)

IV fluids may be needed in large volumes before and after surgery. Adjuvant hyperbaric oxygen therapy may also be of benefit; however, evidence of its effectiveness is inconclusive. IV immune globulin has been suggested for streptococcal toxic shock syndrome with NSTI.

Pearls & Pitfalls

  • If findings suggest necrotizing soft tissue infection, arrange for surgical treatment without delay for testing, and institute IV fluid and antibiotic therapy. The most common error is insufficient surgical intervention.

Key Points

  • Necrotizing soft tissue infection (NSTI) can develop from a contiguous ulcer or infection, hematogenous spread, or after trauma.

  • Consider NSTI in patients with characteristic findings or pain out of proportion to clinical findings, particularly patients with diabetes or other risk factors.

  • Arrange surgical therapy while instituting IV fluid and antibiotic therapy and without delaying for testing.

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