What causes necrotizing fasciitis, particularly in individuals with compromised immune systems, such as those with diabetes, cancer, or HIV/AIDS?

Causes of Necrotizing Fasciitis

Necrotizing fasciitis is caused by bacterial invasion of the subcutaneous tissues and fascia, classified into two main types: polymicrobial infections (Type I, accounting for approximately 53.9% of cases) involving mixed aerobic and anaerobic organisms from bowel or skin flora, and monomicrobial infections (Type II) predominantly caused by Streptococcus pyogenes (Group A Streptococcus), with both types occurring more frequently in immunocompromised patients including those with diabetes, HIV/AIDS, cancer, alcoholism, and other conditions causing impaired cellular immunity. 1, 2, 3

Bacterial Pathogens by Type

Type I: Polymicrobial Necrotizing Fasciitis

• Involves an average of 5 pathogens per wound, with up to 15 different organisms identified, predominantly originating from bowel flora including coliforms (such as Escherichia coli) and anaerobic bacteria 1, 2
• Most commonly associated with four specific clinical settings: perianal abscesses, penetrating abdominal trauma or bowel surgery, decubitus ulcers, injection sites in illicit drug users, and spread from genital sites such as Bartholin abscess or episiotomy wounds 2
• Streptococci, Staphylococci, and E. coli are the most frequently isolated organisms in polymicrobial infections 1, 3

Type II: Monomicrobial Necrotizing Fasciitis

• Streptococcus pyogenes (Group A Streptococcus) is the predominant pathogen, particularly in cases arising after varicella or trivial injuries such as minor scratches and insect bites 1, 2, 3
• This organism carries mortality rates of 30-70% when accompanied by hypotension and organ failure 2
• Staphylococcus aureus (including MRSA) occurs less frequently as a primary organism but can occur simultaneously with streptococci 1, 2
• Other monomicrobial causes include Vibrio vulnificus (in specific exposure contexts such as seawater or raw seafood), Aeromonas hydrophila (water-related exposures), and anaerobic streptococci (Peptostreptococcus species) 1, 2

Type III: Gram-Negative Monomicrobial

• Caused by Gram-negative strains such as Clostridium difficile or Vibrio species 4

Predisposing Conditions and Risk Factors

Immunocompromised States

• Diabetes mellitus is the most frequently associated comorbidity, present in 70.8% of cases, representing the single most important risk factor 1, 3, 4
• All conditions resulting in impaired host resistance from reduced cellular immunity increase risk, including alcoholism, HIV/AIDS, leukemia, and other malignancies 1, 5, 6
• Immunosuppressed patients on chronic corticosteroids or chemotherapy are at elevated risk 5, 6

Other High-Risk Conditions

• Obesity is frequently associated with necrotizing fasciitis, particularly Fournier's gangrene 1
• Peripheral vascular disease and venous insufficiency with edema predispose to infection 1, 6
• Intravenous drug abuse creates injection site portals of entry 2, 5, 6

Pathophysiology and Portal of Entry

Mechanism of Tissue Invasion

• The pathophysiology begins with localized infection allowing entrance of normally commensal bacteria into the subcutaneous tissues 1
• The subsequent inflammatory response results in obliterative endarteritis with thrombosis of surrounding vessels and critical reduction in blood flow 1
• Tissue ischemia promotes further anaerobic bacteria proliferation, fascial necrosis, and tissue digestion 1

Routes of Bacterial Entry

• Extension from a skin lesion occurs in 80% of cases, with the initial lesion often being trivial—such as a minor abrasion, insect bite, injection site, or boil 1
• The remaining 20% of patients have no visible skin lesion, suggesting hematogenous spread from a distant site of infection 1, 6
• Specific anatomic sites of origin in Fournier's gangrene include perineal skin (24%), colorectal region (21%), and genitourinary tract (19%), with unknown origin in 36% of cases 1

Critical Diagnostic Pitfall

Surface cultures of wounds are not valuable as they represent colonizing microbes rather than the underlying etiologic agent; tissue biopsies from deep tissues after thorough debridement or specimens obtained during operation provide definitive bacteriologic diagnosis 2. Gram stain of deep tissue exudate provides early clues to the causative pathogen, with gram-positive cocci in chains suggesting Streptococcus organisms 2.