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Clostridial Gas Gangrene: Background, Pathophysiology, Epidemiology

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Overview

Background

Clostridial gas gangrene is a highly lethal necrotizing soft tissue infection of skeletal muscle caused by toxin- and gas-producing Clostridium species. The synonym clostridial myonecrosis better describes both the causative agent and the target tissue. Prior to the advent of antibiotics and mobile army surgical hospitals, as many as 5% of battlefield injuries were complicated by this condition. However, the incidence rate dropped to less than 0.01% during the Vietnam War. [1] Ninety percent of contaminated wounds demonstrate clostridial organisms, but fewer than 2% develop clostridial myonecrosis. This underscores the importance of host and local wound factors in the development of this process, rather than the mere presence of the organisms in the wound.

Clostridial myonecrosis may occur following surgery, most often of the gastrointestinal or biliary tract, and following septic abortions. [2] Clostridium perfringens, Clostridium septicum, and Clostridium histolyticum are the principal causes of trauma-associated gas gangrene, and their incidence increases dramatically in times of war, hurricanes, earthquakes, and other mass-casualty conditions. [1] There has been an increased incidence of spontaneous gas gangrene caused by C septicum in association with gastrointestinal abnormalities and neutropenia. [3]

Similarly, since the early 2000s, a toxic shock–like syndrome associated with Clostridium sordellii infection has been increasingly recognized in individuals skin-popping black tar heroin and in women undergoing childbirth or other gynecologic procedures, including medically induced abortion. [3]

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Pathophysiology

Clostridia are gram-positive, anaerobic, spore-forming bacilli commonly found throughout nature (with the exception of the North African desert). Cultivated rich soil has the highest density of organisms. In addition, clostridia have been isolated from normal human colonic flora, skin, and the vagina. More than 150 Clostridium species have been identified, but only 6 have been demonstrated to be capable of producing the fulminant condition known as clostridial gas gangrene. Usually, more than 1 species is isolated from clinical specimens. A study by Mendez et al suggests that sugar may inhibit the production of alpha and theta toxins that trigger the gas. [4]

Clostridium perfringens, previously known as Clostridium welchii, is the most common cause of clostridial gas gangrene (80-90% of cases). Other clostridia species responsible for the condition include Clostridium novyi (40%), Clostridium septicum (20%), Clostridium histolyticum (10%), Clostridium bifermentans (10%), and Clostridium fallax (5%).

Infections are characterized by a very low level of host inflammation in response to organism-associated exotoxins. In fact, it is more of a response to the exotoxins than a classic immune response to invading organisms. Purulence often is absent. The process of myonecrosis can spread as fast as 2 cm/h. This results in systemic toxicity and shock that can be fatal within 12 hours. Overwhelming shock with accompanying renal failure usually leads to death.

Infection requires 2 conditions to coexist. First, organisms must be inoculated into the tissues. Second, oxygen tension must be low enough for the organisms to proliferate. These organisms are not strict anaerobes; 30% oxygen tension in the tissues allows for free growth of these bacteria, but 70% oxygen tension restricts their growth. Inoculation of organisms into low oxygen tension tissues is followed by an incubation period that usually ranges from 12 to 24 hours. However, this period can be as brief as 1 hour or as long as several weeks. The organisms then multiply and produce exotoxins that result in myonecrosis.

Although not very well understood, exotoxins appear to be tissue-destructive soluble antigens produced by clostridia. They include lecithinase, collagenase, hyaluronidase, fibrinolysin, hemagglutinin, and hemolysin toxins. C perfringens produces at least 17 identifiable exotoxins that are used for species typing (eg, type A, type B, type C).

Theta toxin causes direct vascular injury, cytolysis, hemolysis, leukocyte degeneration, and polymorphonuclear cell destruction. These effects on leukocytes may explain the relatively minor host inflammatory response that is observed in tissues of patients with clostridial myonecrosis.

Kappa toxin, also produced by C perfringens, is a collagenase that facilitates the rapid spread of necrosis through tissue planes by destroying connective tissue.

Alpha toxin is produced by most clostridia and has phospholipase C activity. This potent lecithinase causes lysis of red blood cells, myocytes, fibroblasts, platelets, and leukocytes. It also may decrease cardiac inotropy and trigger histamine release, platelet aggregation, and thrombus formation. [5]

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Epidemiology

Frequency

United States

Approximately 1000 cases of clostridial gas gangrene are reported per year.

International

Although no published data exist, prevalence is most likely higher in countries other than the United States because of lack of access to health care in other parts of the world.

Mortality/Morbidity

If properly treated, the overall mortality rate is 20% to 30%. If untreated, the process is 100% fatal.

Spontaneous cases carry a mortality rate of 67% to 100%.

With trunk involvement, the mortality rate is higher (60%) than the mortality rate associated with involvement of the extremities, which carries a better prognosis.

A longer incubation period, presence of significant comorbidities, and development of shock increase the risk for mortality.

Race

No race predilection exists.

Sex

No sex predilection exists.

Age

Age does not seem to be an independent risk factor. However, because elderly individuals more often have significant comorbidities, they are at higher risk for mortality than younger patients.

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Prognosis

Most patients do fairly well if they survive the initial critical period.

Shock in patients presenting with clostridial myonecrosis portends a worse prognosis.

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Author

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Charles V Sanders, MD Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine in New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for Physician Leadership, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physicians, American Federation for Medical Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Society of America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, The Scientific Research Honor Society, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, Southwestern Association of Clinical Microbiology, The Foundation for AIDS Research

Disclosure: Receives royalties from Baxter International for: Takeda-receives royalties; UpToDate-receives royalties.

Chief Editor

John Geibel, MD, MSc, DSc, AGAF Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, Professor, Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow; Fellow of the Royal Society of Medicine

John Geibel, MD, MSc, DSc, AGAF is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, Society for Surgery of the Alimentary Tract

Disclosure: Nothing to disclose.

Additional Contributors

Don R Revis, Jr, MD Consulting Staff, Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Florida College of Medicine

Don R Revis, Jr, MD is a member of the following medical societies: American College of Surgeons, American Society for Aesthetic Plastic Surgery, American Society of Plastic Surgeons, American Medical Association

Disclosure: Nothing to disclose.