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Last updated:
May 07, 2018
Years published: 2018
NORD gratefully acknowledges Michael Mallozzi, PhD, Animal and Comparative Biomedical Sciences, University of Arizona, and the Gut Check Foundation, for assistance in the preparation of this report.
Clostridial myonecrosis is a serious, life-threatening bacterial infection caused by a small number of Clostridium species of bacteria. Clostridial myonecrosis is broken down into two main forms – traumatic and spontaneous – and the two species most commonly associated with this infection are Clostridium perfringens, which is the primary cause of the traumatic form, and Clostridium septicum, which is the primary cause of the spontaneous form. The traumatic form most often arises in individuals who have suffered an injury or trauma that hinders or limits blood supply to the area (vascular compromise). The spontaneous form is often associated with individuals whose immune system are weakened or suppressed usually due to an underlying medical condition, most often cancer of the colon or rectum. Other underlying conditions that can be associated with the spontaneous form include blood (hematological) cancers like leukemia, diabetes mellitus, cyclic neutropenia, or individuals whose immune system is suppressed for other reasons. Clostridium septicum is not part of the normal human gut microbiota. It is thought that the associated illnesses cause maladaptation and imbalance (dysbiosis) allows Clostridium septicum to populate the gut. The bacteria can exist within the gastrointestinal system, but are kept under control by the immune system. In some immune-suppressed individuals, the infection can become dangerous.
Clostridial myonecrosis is the term used when these clostridial infections spread to affect deep muscle tissue. A variety of complications can develop including pain, gas gangrene (a condition in which gas production and build up within muscle tissue leads to tissue death [necrosis]), and sepsis, a severe blood infection. These infections eventually progress to cause toxic shock and multiple organ failure. Clostridial myonecrosis is a rapidly progressive, medical emergency that can be fatal despite treatment. Prompt diagnosis and aggressive treatment are essential.
Pain is often the presenting symptom and may be severe and may develop rapidly. In individuals with Clostridium perfringens infection following surgery, pain may arise shortly after the surgical procedure and be disproportionately strong. In Clostridium septicum infection, there is often sudden, severe onset of muscle pain. Sometimes, there is a sensation of heaviness, pressure, or numbness. Some individuals with the spontaneous form may initially show signs of confusion or exhibit a general feeling of poor health (malaise).
In addition to pain, general early signs and symptoms can include fever, fatigue, and dehydration.
Clostridial myonecrosis can cause a specific condition called gas gangrene. Clostridial infection produces toxins in the body. These toxins produce a gas. This gas becomes trapped within deep muscle tissue, specifically the soft tissues. This contributes to tissue death and decay called necrosis.
Because clostridial myonecrosis affects deep muscle tissue initially, the skin near the infection site may be unaffected at first. Eventually, the skin may become pale, and over time usually darkens to reddish or brownish color. Eventually, bullae may form. Bullae are air- or fluid-filled sacs that form under a thin layer of skin. Sometimes, air- or blood-filled blisters called blebs form. Ultimately, the skin may turn a black or dark green color. The affected area may be extremely painful or tender, and there may be a grating or crackling sound (crepitation) from underneath the skin.
Other signs and symptoms can include a foul-smelling discharge from the infection site, localized hardening of affected soft tissue (induration), and swelling due to fluid accumulation (edema). Eventually, the skin may break down and liquify before shedding off (sloughing).
Sometimes, an infection can spread to the aorta, the main artery of the body. This is called aortitis. The wall of the artery may balloon or bulge outward (aneurysm) and there is a risk of the aorta rupturing.
As the infection progresses, sepsis may occur. Sepsis is a widespread blood infection, in which the infections spreads to other areas of the body. The body responds by releasing chemicals to fight off the infection. These chemicals bring about an inflammatory response in the body. Individuals with sepsis can develop a rapid heartbeat (tachycardia), abnormally rapid breathing (tachypnea), low blood pressure (hypotension), and changes in their mental status including greatly dulled awareness or consciousness (stupor). Sepsis can lead to toxic shock, a life-threatening condition characterized by a sudden, high fever, sore throat, vomiting, diarrhea, muscle aches, headaches, confusion, disorientation, a rash, and seizures. Ultimately, multiorgan failure can occur.
Clostridial myonecrosis is caused by infection with species of the Clostridium genera of bacteria. Clostridia are found throughout nature. They are found in soil and marine sediments and can be found in animal and human gastrointestinal tracts. Two specific species, Clostridium perfringens and Clostridium septicum account for most of the people who develop clostridial myonecrosis. These two species produce toxins that cause certain cells to breakdown prematurely and damage blood vessels. They may promote the formation of blood clots and decrease or depress heart muscle contractions. These toxins also produce a gas that becomes trapped within deep muscle tissue causing tissue death and decay (myonecrosis or gas gangrene).
Clostridium infection can occur in individuals who have recently experienced trauma or surgery. This is known as the trauma and or wound-related form. It is most often caused by Clostridium perfringens. An individual is exposed to the bacteria through the open wound. However, the bacteria will not grow and spread unless the environment around the wound will support its growth and spread. These bacteria do not need oxygen to survive and, if the injury or wound limits or hinders blood supply to the affected area, this can create an environment that promotes the growth and spread of the bacteria. The bacteria will spread to surrounding tissue including deep muscle tissue. The traumatic form of clostridial myonecrosis is associated with a variety of traumatic conditions including gunshot or deep knife wounds, compound fractures, and intramuscular injections. It may also be associated with bowel and biliary tract surgery or abortions. Pregnant women who have a retained placenta or prolonged rupture of fetal membranes or experience the death of a fetus (intrauterine fetal demise) may also be at risk.
The spontaneous form of infection occurs when there is no obvious route of infection. It is also called the nontraumatic or idiopathic form. It is usually caused by Clostridium septicum and usually develops in individuals with a suppressed immune system and cancer of the colon or rectum. It also occurs in individuals with blood cancers like leukemia, inflammatory bowel disease, diverticulitis, lymphoproliferative disorders, cyclic neutropenia, or acquired immune deficiency syndrome (AIDS). Individuals who have undergone radiation therapy or gastrointestinal surgery may also be at risk. It is thought, the infection enters the bloodstream through an injury or lesion within the gastrointestinal system where it is carried to other tissues of the body including deep muscle tissue (hematogenous muscle seeding). Clostridium septicum does not need a low oxygen environment to grow and spread in the body and it is more aerotolerant than Clostridium perfringens.
Clostridial myonecrosis is a rare infection. Approximately, one in 1,000-3,000 people are reported each year in the United States. Most affected individuals are adults, but these infections can occur in individuals of any age including children. About 80% of these infections are traumatic clostridial myonecrosis. Of these, about 70% are caused by Clostridium perfringens.
A diagnosis of clostridial myonecrosis is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests including a culture positive patient sample.
Certain physical signs may support a diagnosis of traumatic clostridial myonecrosis. These include pain at the site of a wound or surgery, and signs of systemic toxicity or gas in the soft tissues such as a grating or crackling sound (crepitation) from underneath the skin. Spontaneous clostridial myonecrosis may be suspected in individuals with rapid onset of pain and fever, particularly in the arms and legs, in the absence of trauma or injury. The traumatic form easier to diagnose.
Clinical Testing and Workup
Blood tests can reveal findings that are indicative of clostridial myonecrosis. Muscle damage and loss can lead to elevated levels of aldolase, potassium, lactate dehydrogenase, and creatine phosphokinase levels. White blood cell levels may be low. Sometimes, anemia (low levels of red blood cells) is seen.
X-rays may reveal fine gas bubbles in affected soft tissue and skin tissue. Specialized imaging techniques called computerized tomography (CT) scanning and magnetic resonance imaging (MRI) can reveal gas outside of the gastrointestinal tract (extraluminal gas). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily issues. CT scanning and MRIs can also be used to determine whether an infection is localized to one site of the body or has spread to other areas.
Laboratory technicians will also run a test called a Gram stain. Bacteria may be classified as “Gram negative” or “Gram positive”, depending upon the results of the staining test. This method involves staining bacteria with various solutions and dyes that help to identify and classify the bacteria based on the composition of their cellular components. This rapid staining technique when combined with microscopy gives physicians early clues about the underlying cause of their patient’s conditions. In individuals with clostridial myonecrosis, a Gram stain of discharge from the wound may reveal “Gram positive” rods (rod-shaped bacteria) and the absence of polymorphonuclear cells. These cells are inflammatory cells that are normally found at the sites of injury within the body, but are not found when this clostridial infection is involved. Researchers believe that toxins produced by some members of the infectious Clostridia prevent polymorphonuclear cells from reaching infected tissue.
Blood cultures, which are tests that can detect and classify bacteria found in the blood, may be useful for diagnosing spontaneous clostridial myonecrosis and Clostridial septicum infection. Bacteria in the blood usually precedes skin signs by several hours.
Exploratory surgery of the wound may reveal characteristic findings including muscles that do not bleed or contract upon stimulation, swelling, and discoloration. A tissue sample may be removed and studied under a microscope (biopsy sample) to other characteristic changes in muscle tissue.
Clostridial myonecrosis is a medical emergency. Early diagnosis and prompt therapy are essential for the best outcome. Treatment may require a team of specialists including a specialist in diagnosing and treating infectious diseases (infectious disease specialist); a specialist in diagnosing and treating skin disorders (dermatologists); general, trauma, or burn surgeons; plastic surgeons; social workers; and other healthcare professionals may need to systematically and comprehensively plan treatment. Psychosocial support for the entire family is essential as well.
The initial treatment for infection includes urgent surgical removal of all affected dead (necrotic), damaged or infected skin and subcutaneously tissue involved. This allows the remaining healthy tissue to heal more effectively. This is called debridement or surgical debridement and may require repeated sessions to maintain the wound margins as necessary over time. In severe instances, debridement can lead to the removal of a large portion of skin or tissue, or, when there is a severe infection of an arm or leg, amputation of the affected limb in order to stop the spread of infection.
Along with debridement affected individuals are prescribed broad-spectrum intravenous antibiotics as quickly as possible. Antibiotics are medications that inhibit the growth of and destroy bacteria and are essential in controlling sepsis and preventing the spread of the infection. Broad spectrum antibiotics works against both gram-positive and gram-negative bacteria (see Diagnosis above) and are recommended until a definitive diagnosis is reached.
Large clinical trials to test the effectiveness of different antibiotic medication for the treatment of clostridial myonecrosis have not been conducted. In 2014, the Infectious Disease Society published practice guidelines for the diagnosis and management of skin and soft tissue infections (Stevens, et al 2014). Penicillin plus clindamycin or tetracycline, are the recommended antibiotic regimen for clostridial myonecrosis.
Supportive therapies are also essential and can include intravenous fluids and supplemental oxygen. If affected individuals have not received immunization against tetanus within 10 years, then a booster vaccination against tetanus may be recommended.
Hyperbaric oxygen (HBO) therapy has been studied for clostridial myonecrosis, but its use is controversial. There have not been clinical trials on a large group of patients, but some small, nonrandomized trials have reported good results when HBO is combined with antibiotic therapy and surgical debridement. HBO involves exposing the patient to pure oxygen in a pressure room or medical tube and has been effective in treating other types of serious infection. There is some research that shows that hyperbaric conditions inhibit infection and the production of toxins by clostridia. However, there are risks with HBO therapy including the need to move a patient out of intensive care where emergency intervention can be provided. More research is necessary to determine the long-term safety and effective of hyperbaric oxygen therapy and whether the therapy has a role in treating individuals with clostridial myonecrosis.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Mallozzi, Michael JG, et al. Trusting Your Gut: Diagnosis and Management of Clostridium septicum Infections.
Clinical Microbiology Newsletter, Volume 38, Issue 23, 187 – 191
Srivastava I, Aldape MJ, Bryant AE, Stevens DL. Spontaneous C. septicum gas gangrene: A literature review. Anaerobe. 2017;48:165-71.
Burnham JP, Kollef MH. Treatment of severe skin and soft tissue infections: a review. Curr Opin Infect Dis. 2018;31:113-119. https://www.ncbi.nlm.nih.gov/pubmed/29278528
Jessamy K, Ojevwe FO, Ubagharaji E, et al. Clostridium septicum: an unusual link to a lower gastrointestinal bleed. Case Rep Gastroenterol. 2016;10:489-493. https://www.karger.com/Article/FullText/448881
Shah A, Yousuf T, Rachid M, et al. Clostridium septicum aortitis of the infrarenal abdominal aorta. J Clin Med. 20016;8:168-174. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701074/
Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infectious: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59:e10-52. https://academic.oup.com/cid/article/59/2/e10/2895845
El Sayad M, Chikate A, Ramesh B. Gas gangrene presenting with back pain. BMJ Case Rep. 2014;2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025197/
Stevens DL, Aldape M, Bryant AE. Life-threatening clostridial infections. Anaerobe. 2012;18:254-259. https://www.ncbi.nlm.nih.gov/pubmed/22120198
Khalid M, Lazarus R, Bowler ICJW, Darby C. Clostridium septicum and its implications. BMJ Case Rep. 2012;2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4543009/
Bryant AE, Stevens DL. Clostridial myonecrosis: new insights in pathogenesis and management. Curr Infect Dis Rep. 2010;12:383-391. https://www.ncbi.nlm.nih.gov/pubmed/21308521
Smith-Slatas CL, Bourque M, Salazar JC. Clostridium septicum infections in children: a case report and review of the literature. Pediatrics. 2006;117:e796-805. https://www.ncbi.nlm.nih.gov/pubmed/16567392
INTERNET
Stevens DL, Bryant A. Clostridial Myonecrosis. UpToDate, Inc. 2017 Oct 3. Available at: https://www.uptodate.com/contents/clostridial-myonecrosis Accessed April 5, 2018.
Qureshi S. Clostridial Gas Gangrene. Emedicine Journal, January 18, 2017. Available at: Accessed April 10, 2018.
https://emedicine.medscape.com/article/214992-overview Accessed April 10, 2018.
Tidy C. Patient website. Gas Gangrene. Mar 12, 2014. Available at: https://patient.info/doctor/gas-gangrene Accessed April 10, 2018.
Mayo Clinic for Medical Education and Research. Hyperbaric Oxygen Therapy. January 12, 2018. Available at: https://www.mayoclinic.org/tests-procedures/hyperbaric-oxygen-therapy/about/pac-20394380 Accessed April 10, 2018.
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