Background
Gas gangrene, a subset of necrotizing myositis, is an infectious disease emergency associated with extremely high morbidity and mortality. Organisms in the spore-forming clostridial species, including Clostridium perfringens, Clostridium septicum, and Clostridium novyi, cause most of the cases. A nonclostridial form is caused by a mixed infection of aerobic and anaerobic organisms. The hallmarks of this disease are rapid onset of myonecrosis with muscle swelling, severe pain, gas production, and sepsis. [1, 2]
Pathophysiology
Clostridium species are gram-positive, spore-forming, anaerobic rods normally found in soil and the gastrointestinal tract of humans and animals. They most often cause disease in the setting of trauma or surgery but can also occur spontaneously in the absence of definite risk factors or exposures. [3] Not all wounds contaminated with clostridia develop gas gangrene; the myonecrosis seems to only develop when sufficient devitalized tissue is present to support anaerobic metabolism. [2]
Traumatic gas gangrene and surgical gas gangrene occur through direct inoculation of a wound. With a compromised blood supply, the wound has an anaerobic environment that is ideal for C perfringens, the cause of the vast majority of cases of gas gangrene. [4] Additionally, while C perfringens cannot grow in the presence of oxygen, it is relatively resistant to killing by oxygen. This, along with its extremely rapid doubling time make it highly virulant. [4] The degredation of host tissues and rapid transport of nutrients into bacterial cells from the host tissues produces abundant gas from the anaerobic glycolysis pathway resulting in even more improved conditions for growth. [5]
Spontaneous gas gangrene is most often caused by hematogenous spread of C septicum from the gastrointestinal tract in patients with colon cancer or other portals of entry. Neutropenic immunocompromised patients, patients who have undergone prior radiation therapy to the abdomen, and those with vascular compromise are also at risk. The organism enters the blood via a small break in the gastrointestinal mucosa and subsequently seeds muscle tissue. Unlike C perfringens, C septicum is aerotolerant and can infect normal tissues. C perfringens and C histolyticum are more commonly associated with trauma. [6]
With C perfringens, the local and systemic manifestations of infection are due to the production of potent extracellular protein toxins by the bacteria. [36] These are most notably alpha-toxin (a phospholipase C) and theta-toxin (a thiol-activated cytolysin), also known as perfringolysin O (PFO). These toxins often function synergistically. They hydrolyze cell membranes, cause abnormal coagulation leading to microvascular thrombosis (further extending the borders of devascularized and thus anaerobic tissue), and have direct cardiodepressive effects. The pathogenesis of C perfringens tissue necrosis is characterized by a lack of acute inflammatory cells such as polymorphonuclear neutrophils (PMNs) and vascular leukostasis in the tissues, leading to a rapid progression of infection. In contrast, other soft-tissue infection caused by bacteria such as Staphylococcus aureus and Streptococcus pneumoniae has a robust presence of PMNs at the site of infection, leading to minimal tissue destruction. [7] Furthermore, the products of tissue breakdown seen in C perfringens infection, including creatine phosphokinase, myoglobin, and potassium, may cause secondary toxicity and renal impairment. [8]
Significant and refractory anemia may also be present in patients with gas gangrene. This effect is a direct consequence of toxin-mediated hemolysis of RBCs when significant amounts of alpha toxin are released into the bloodstream. Alpha toxin has negative inotropic effects on cardiac myocytes contributing to the severe, refractory hypotension seen in some cases of gas gangrene. Theta toxin causes a cytokine cascade, which results in peripheral vasodilation similar to that seen in septic shock. Vaccination of experimental animals against alpha and theta toxins substantially decreases the severity of infection.
Epidemiology
Frequency
United States
Estimates of incidence of gas gangrene vary; however, with improvements in surgical technique and wound care, cases are relatively rare. Data estimate 1000 cases per year in the United States or 0.03-5.2% of open wounds, depending on type of wound and treatment. Clostridial contamination of wounds may be common, although in the absence of deep injury or significant devitalized tissue, myonecrosis and productive infection do not typically occur.
International
No data are published, but incidence is probably higher internationally than in the United States. Incidence is highest in areas with poor access to proper wound care. The incidence of surgically acquired infection is higher in areas where sterile technique and surgical hygiene may be imperfect.
Mortality/Morbidity
Mortality from traumatic gas gangrene is 20-30% if early and effective care is provided.
Mortality from nontraumatic gas gangrene caused by C septicum ranges from 67-100%.
Age
Occurrence is not age specific.
Diabetic peripheral vascular disease and other chronic immunocompromised states that can predispose individuals to gas gangrene are more prevalent in older populations. [9, 10]
Prognosis
Clostridial infections are more likely to result in limb loss and mortality than other soft-tissue infections. If the infection involves the chest wall, the mortality rate is 2-12 times higher than extremity infections. [6] Early diagnosis and aggressive treatment of gas gangrene are the keys to decreasing mortality. Retrospective analysis of all necrotizing soft-tissue infections indicates that a delay to surgery of greater than 12 hours suggests a 3-fold increased risk of developing septic shock and a 6-fold increased risk of mortality. [11]
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Left lower extremity in a 56-year-old patient with alcoholism who was found comatose after binge drinking. Surgical drainage was performed to treat the pyomyositis-related, large, non–foul-smelling (sweetish) bullae. Gram staining showed the presence of gram-positive rods. Cultures revealed Clostridium perfringens. The diagnosis was clostridial myonecrosis.
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A patient developed gas gangrene after injecting cocaine. Clostridium septicum was isolated in both blood and wound cultures.
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Gas feathering in the arm soft tissue of a patient with gas gangrene.
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Extension of gas gangrene to the chest wall despite initial debridement.
