Gas Gangrene

Gas gangrene, also known as clostridial myonecrosis, is a life-threatening muscle and soft tissue infection that usually develops after traumatic inoculation with Clostridium perfringens (C. perfringens), but can also develop spontaneously in association with other Clostridium species. Sudden, severe muscle pain classically develops shortly after the injury. Skin color changes (red/purple to black), tenderness, bullae formation, and crepitus are also present and progress rapidly. Most of the time, diagnosis is established clinically. Once the diagnosis is suspected, intravenous (IV) antibiotic therapy should be started and emergent surgical debridement should be performed.

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Overview

Definition

Gas gangrene (clostridial myonecrosis) is a rapidly progressing infection of muscle and soft tissue most commonly caused by Clostridium species.

Epidemiology

  • Cultivated land has Clostridium species widely distributed in the soil.
  • U.S. incidence of gas gangrene: about 1,000 cases/year
  • Worldwide cases are suspected to be much higher than the United States but underreported due to lack of healthcare.

Etiology

  • Clostridium perfringens (C. perfringens) makes up > 80% of gas gangrene infections.
  • C. perfringens is an anaerobic gram-positive bacillus.
  • Other pathogens include C. septicum and C. histolyticum.
  • 2 major presentations:
    • Traumatic (70%; major pathogen C. perfringens): 
      • Gunshot or stab wounds
      • Compound fractures or crush injuries
      • Bowel and biliary surgery
      • Abortion/retained placenta/prolonged rupture of the membranes
      • Intrauterine fetal demise
      • Intramuscular injection
      • Black tar heroin injection
    • Spontaneous: major pathogen C. septicum
  • Immunocompromised state (e.g., diabetes mellitus) is an important risk factor.

Pathophysiology and Clinical Presentation

Traumatic gas gangrene

  • Organisms get introduced into the tissues (through open wounds, during surgery).
  • Not every contamination results in infection.
  • Infection usually happens when there is compromised blood supply or devitalized tissue.
  • Conditions needed for C. perfringens to propagate:
    • Anaerobic environment
    • Acidic pH
  • Severe progressive tissue necrosis develops due to exotoxins produced by C. perfringens:
    • Alpha-toxin:
      • Hemolytic toxin; essential for disease manifestations and mortality
      • Has phospholipase C and sphingomyelinase activity
      • Degrades tissue and cell membranes
      • Causes small vessel thrombosis and tissue ischemia
      • Ischemia creates anaerobic environment → further propagation of C. perfringens
      • Also depresses cardiac output and contributes to systemic shock
    • Theta-toxin (perfringolysin O):
      • Pore-forming cytolysin
      • Cytotoxic to vascular and immune cells 
      • Not essential for mortality
  • Important feature: lack of polymorphonuclear leukocytes in affected tissues

Spontaneous gas gangrene

  • Hematogenous seeding of muscle with bacteria
  • Points of entry:
    • Gastrointestinal tract (commonly from colonic adenocarcinomas)
    • Musculoskeletal allografts
  • C. septicum does not need anaerobic conditions and can grow in normal tissues.
  • Disease progression is caused by production of multiple exotoxins.

Clinical presentation

Localized signs and symptoms:

  • Typical incubation period < 24 hours
  • Sudden onset of severe pain
  • Skin color changes: paleness → bronze appearance → purple-to-purple red → black discoloration
  • Tense, tender skin
  • Blistering and bullae development: may be clear fluid or blood filled 
  • Foul-smelling discharge 
  • Crepitus (gas in tissues): very sensitive and specific 

Systemic symptoms:

  • Tachycardia 
  • Hypotension 
  • Fever 
  • Multiorgan failure 
  • Acute renal failure: ↑ creatinine 
  • Liver damage: jaundice and liver necrosis
  • Intravascular hemolysis

Diagnosis

Physical exam

  • Most of the time, an exam is sufficient to establish the diagnosis.
  • Severe pain at the affected site
  • Skin discoloration and blistering
  • Crepitus
  • Systemic toxicity: 
    • Fever
    • Tachycardia/hypotension
    • Change in mental status 

Laboratory studies

  • Histopathology: Gram staining reveals gram-positive or gram-variable rods at the site of the injury (definitive diagnosis).
  • Wound cultures: double zone of hemolysis on blood agar with C. perfringens growth
  • Blood cultures: < 1% of blood cultures in patients with gas gangrene grow clostridial species.
  • Additional laboratory studies can detect: 
    • Hemolysis (anemia, ↑ lactate dehydrogenase, ↑ indirect bilirubin)
    • Leukocytosis
    • Lactic acidosis
    • Elevated creatinine (renal failure)

Imaging

  • X-ray: 
    • Gas in deep tissues
    • Quick and easy to obtain
  • Computed tomography (CT) or magnetic resonance imaging (MRI):
    • More detailed imaging than plain X-ray
    • Takes longer to obtain and may delay management

X-ray reveals soft-tissue gas consistent with gas gangrene.

Image: “Figure 3” by Cooney and Cooney. License: CC BY 2.0

Management

Medical

  • Supportive therapy: 
    • Intravenous (IV) fluid resuscitation
    • Correct electrolytes
    • Blood transfusion 
    • Hyperbaric oxygen therapy: largely experimental 
    • Tetanus toxoid if indicated (in case of traumatic gas gangrene)
  • Antibiotics:
    • Broad-spectrum IV antibiotics should be initiated. 
    • IV antibiotic therapy: 
      • Penicillin 10–24 million U/day plus clindamycin 600 mg, or  
      • Clindamycin and metronidazole for penicillin-allergic patients

Surgical

  • Aggressive surgical debridement needs to be performed as soon as possible.
  • Multiple debridements are typically required.
  • Amputation may be required in case of extremity involvement.
  • Extremities must be monitored for compartment syndrome and may require fasciotomy.

Prognosis

  • The mortality rate can reach 20%–30% with the best care.
  • 100% mortality rate if untreated 
  • Spontaneous infections can have mortality rates as high as 67%.
  • Infections involving the abdominal soft tissue or chest wall have higher mortality than extremity infections.
  • Predictors of mortality:
    • Shock at the time of presentation
    • Presence of malignancy
    • Immunocompromised state

Differential Diagnosis

  • Necrotizing fasciitis (NF): a life-threatening infection involving the fascia and the subcutaneous tissue that results in tissue necrosis and destruction. Patients present with pain out of proportion to the presenting symptoms and a rapidly progressing erythema after an injury. Quickly progresses into septic shock. Thus, aggressive surgical debridement, parenteral antibiotics, and continuous monitoring should be done.
  • Staphylococcal scalded skin syndrome: a blistering skin disorder caused by a local infection usually due to Staphylococcus aureus (S. aureus). Presents with fever and diffuse, tender erythema, intraepidermal blisters, and sloughing off of the superficial layer of skin, leaving a red “scalded” appearance. Management is with admission and IV antibiotics.
  • Cellulitis: a common and painful bacterial skin infection that affects the deeper layers of dermis and subcutaneous tissue. Presents with erythematous, edematous areas that are tender to touch. Caused most commonly by S. aureus and Streptococcus pyogenes (S. pyogenes). Diagnosis is usually clinical and management is antibiotics based on suspected organisms.
  • Bullous pemphigoid and pemphigus vulgaris: autoimmune disorders that cause fluid-filled blisters with rounded skin elevation. Patients with bullous pemphigoid usually present with cutaneous, tense blisters and bullae while patients with pemphigus vulgaris present with cutaneous, flaccid bullae and mucosal erosions. Both conditions require steroid management.

References

  1. Qureshi, S. (2019). Clostridial Gas Gangrene. Emedicine. Retrieved on January 29th, 2021, from https://emedicine.medscape.com/article/214992-overview
  2. Méndez MB, Goñi A, Ramirez W, & Grau RR. (2012). Sugar inhibits the production of the toxins that trigger clostridial gas gangrene. Microb Pathog 52(1):85-91. 
  3. Mandell, D., & Bennett. Gas Gangrene and Other Clostridium-Associated Diseases. Principles and Practice of Infectious Diseases. Eighth edition.
  4. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. (2014). Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of america. Clin Infect Dis 59(2):e10-52. 
  5. Stevens, D., & Bryant, A. (2019). Clostridial myonecrosis. UptoDate. Retrieved on January 28, 2021, from https://www.uptodate.com/contents/clostridial-myonecrosis

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