Clostridial Gas Gangrene

Updated: Feb 01, 2023
Author: Shahab Qureshi, MD, FACP; Chief Editor: John Geibel, MD, MSc, DSc, AGAF 



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]


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]



United States

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


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.


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.


No race predilection exists.


No sex predilection exists.


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.


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

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




Obtaining a thorough medical history is important. It helps the physician identify risk factors that may affect the progression of the disease and the prognosis, and the history should include questions about the following[1] :

  • Pain

    • Increasing pain after surgery or trauma

    • Out of proportion to physical findings

    • Sudden onset

    • May be severe

  • Prior trauma

  • Prior surgery, including abortions

  • Diabetes mellitus

  • Peripheral vascular disease

  • Alcoholism

  • Drug abuse

  • Advanced age

  • Chronic debilitating disease(s)

  • Immunocompromised state

    • Steroid use

    • Malnutrition

    • Malignancy

    • Acquired immunodeficiency syndrome (AIDS)


Perform a thorough physical examination before focusing on the involved body part, as follows:

  • Vital signs - May indicate systemic toxicity and include no or low-grade fever, tachycardia (relative tachycardia), tachypnea, hypotension, or hypoxia

  • Edema bullae

  • Erythema with purplish black discoloration

  • Extreme tenderness

  • Brownish skin discoloration (bronzing, brawny) with bullae

  • Profuse, "dish-watery," serous drainage from ruptured bullae

  • Discharge - May have a peculiar, "mousy," sweet odor

  • Minimal crepitant bullae

  • Crepitant tissue - May extend well beyond any skin discoloration, edema, or bleb formation

  • Mental status - Paradoxically, may be depressed early during the disease course; sensorium then may clear as the disease progresses and the patient is near death


The disease process must include tissue inoculation and a low oxygen tension environment. More than 50% of cases are preceded by trauma.[6, 7] Other cases occur spontaneously or in patients after operative procedures.

  • Trauma

    • Compound fractures

    • Foreign bodies

    • Frostbite

    • Thermal or electrical burns

    • Subcutaneous or intravenous injection of medications or illicit drugs

    • Pressure sores

    • Motor vehicle crashes

  • Postoperative

    • Gastrointestinal tract surgery

    • Genitourinary tract surgery

    • Abortion

    • Amputation

    • Tourniquets, casts, bandages, or dressings applied too tightly

  • Spontaneous

    • This also is known as nontraumatic, idiopathic, or metastatic gas gangrene.

    • It most often is mixed infection caused by C septicum, C perfringens, and C novyi. Several series report a mortality rate that approaches 100%.

    • The gastrointestinal tract is the source of organisms. The organisms escape the bowel by translocation, enter the bloodstream, and seed distant sites where they can cause gas gangrene. This process may also result in a more localized infection that involves the viscera or intra-abdominal compartment.

    • Approximately 80% of patients without trauma have an overt or occult malignancy. Of these, approximately 40% are hematologic malignancies and an additional 34% are colorectal.[8] Survival from this process should initiate a search for an occult malignancy if none has been documented previously in patients without trauma.


Potential complications include the following:

  • Death

  • Amputation

  • Permanent deformity or disability



Laboratory Studies

The white blood cell count may be normal or elevated. Immature forms usually are increased.

Elevated liver function test results may indicate progressive hepatic dysfunction.

Elevated blood urea nitrogen and creatinine may indicate azotemia, renal insufficiency, or renal failure.

Myonecrosis may elevate serum aldolase, potassium, lactate dehydrogenase, and creatine phosphokinase levels.

Profound anemia may result from severe intravascular hemolysis.

Arterial blood gas determinations and chemistry panel analysis may reveal metabolic acidosis.

Disseminated intravascular coagulation may result from exotoxin release.

A Gram stain of the wound discharge reveals gram-positive rods and an absence of polymorphonuclear cells. Other organisms are present in up to 75% of cases. This test is essential for rapid diagnosis.

An assay for sialidases (neuraminidase) produced by clostridia also may be performed on serum and wound discharge. These tests provide rapid (< 2 h) confirmation of Gram stain results.

Most clinical microbiology laboratories use a combination of fermentation reactions and detection of short-chain fatty acid end-products for definitive identification of Clostridium species.

Imaging Studies

Radiographs reveal fine gas bubbles within the soft tissues, dissecting into the intramuscular fascial planes and muscles. Other necrotizing soft tissue infections produce abundant gas, in contrast to the paucity of gas of clostridial gas gangrene.

Intra-abdominal clostridial gas gangrene is evaluated most readily with CT scanning, which demonstrates extraluminal gas.

Other Tests

Blood and bullous fluid cultures reveal clostridia but take at least 48 hours to perform. They are not useful because the delay almost certainly results in death.

Although not widely used by clinical microbiology laboratories, rapid polymerase chain reaction methods for identification of C perfringens are available.[9]

In the future, methods such as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry likely will be used for rapid identification of organisms, including Clostridium species.[10, 11, 12, 13]

Histologic Findings

Histologic analysis reveals necrotic muscle, clostridia, and a minimal inflammatory infiltrate.



Medical Care

Successful therapy requires rapid diagnosis and aggressive early treatment.[7] The physician must maintain a high index of suspicion for this uncommon but potentially fatal process. Clinical distinction in early stages between necrotizing fasciitis and necrotizing soft tissue infection is undetectable.[14]  Any patient in whom clostridial gas gangrene is suspected should be considered critically ill.

Obtain early consultation with a surgeon for debridement.

Administer supplemental oxygen.

Restore intravenous fluid volume and monitor urine output with an indwelling bladder catheter.

Transfer to an intensive care unit that has telemetry and pulse oximetry.

Ensure that tetanus immunity is adequate.

Antibiotic therapy

Broad-spectrum empiric antibiotic treatment is warranted to cover group A Streptococcus, Clostridium species, and mixed aerobes and anaerobes.

Definitive antibiotic therapy should consist of the combination of penicillin plus clindamycin or tetracycline. Optimal duration of therapy has not been defined, and it should be continued until no further debridement is planned and hemodynamic stability has been achieved.

Antibiotics against C septicum in animal models demonstrated higher susceptibility to penicillin, clindamycin, and tetracycline, but considerably lower susceptibility to vancomycin.[15]

Hyperbaric oxygen therapy

The role of hyperbaric oxygen (HBO) treatment as adjunctive therapy remains controversial. Some nonrandomized studies have reported good results with HBO therapy when combined with antibiotics and surgical debridement.[16]

Clostridia lack superoxide dismutase, making them incapable of surviving in the oxygen-rich environment created within a hyperbaric chamber. This inhibits clostridial growth, exotoxin production, and exotoxin binding to host tissues.

Hyperbaric oxygen also therapy may promote host polymorphonuclear cell function.

Animal studies have clearly demonstrated a survival advantage when this therapy is combined with antibiotics and debridement. However, no randomized controlled studies of humans exist to support this finding.

Hyperbaric oxygen should be used at the discretion of the treating physician but should never cause a delay in surgical debridement. Transporting a patient from one facility to another merely to administer hyperbaric oxygen probably is not warranted and may be detrimental.

Administer therapy 3 times a day for 2 days, then twice a day for several more days, until the disease process is well under control.

The dose is usually 2.5 atmospheres absolute (ATA) oxygen for 120 minutes or 3 ATA oxygen for 90 minutes. The pressure at sea level equals 1 ATA.

Complications include fire, seizures, decompression sickness, middle ear barotrauma, and claustrophobia.

Future management

Future treatment strategies may include attenuation of toxin-induced vascular leukostasis and resultant tissue injury by targeting endogenous proadhesive molecules and reducing duration and severity of shock via anti-cytokine molecules.

Treatment guidelines

The reader is also referred to the 2014 guidelines published by the Infectious Diseases Society of America (IDSA) for the treatment of clostridial gas gangrene (see Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America).[17]

Surgical Care

Clostridial gas gangrene represents a true surgical emergency.

It requires prompt aggressive debridement of all involved tissues.

Extensive extremity involvement may require amputation.

Because the disease process may continue to involve additional tissue, daily exploration and further debridement may be necessary.

Wound exploration reveals gas, watery discharge, and necrotic muscle. Muscle tissue may be pale, edematous, and may not bleed when cut or contract when stimulated with electricity.

If the patient survives, the wound may be closed at a later date or allowed to heal secondarily (by wound contraction and spontaneous re-epithelialization).


Consultations are as follows:

  • Infectious disease specialists

  • General, trauma, or burn surgeon

  • Plastic surgeon


Ensure that the patient receives adequate nutritional support during this period of increased energy requirements.

During the period of critical illness, administration of enteral or parenteral nutrition may be required.

Consultation with a nutritionist ensures optimal nutritional replacement.

Frequently monitor nutritional status through serum markers and nitrogen balance determination.


Once patients have survived the critical period of illness, they may benefit from occupational or physical therapy to restore preinjury function.

Further Inpatient Care

If patients survive, they typically are hospitalized for several weeks.


Transfer is required infrequently and may be detrimental to the patient.

As long as the treating facility has the capability and experience to provide adequate surgical and intensive care, no transfer is necessary.

Transfer merely to obtain access to hyperbaric oxygen therapy is not indicated.



Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.


Class Summary

Penicillin is the preferred drug for clostridial infections. Patients allergic to penicillin may be treated with clindamycin or chloramphenicol.

Penicillin G (Pfizerpen)

Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Piperacillin/tazobactam (Zosyn)

Beta-lactamase inhibitor indicated in gynecologic infections, intra-abdominal infections, and skin and skin structure infections, including diabetic foot infections.

Metronidazole (Flagyl, Metro)

Exact mechanism of action not fully elucidated. Disrupts DNA and inhibits nucleic acid synthesis.

FDA approved for the treatment of anaerobic infections: intra-abdominal infections, skin and skin-structure infections, and bone and joint infections.


Inhibits bacterial protein synthesis. May also cause alterations in the cytoplasmic membrane. Bacteriostatic antibiotic.

Alternative in PCN-allergic patients. 


Inhibits protein synthesis by binding to 50S ribosomal subunits, preventing amino acids from being transferred to the growing peptide chains, which in turn inhibits protein synthesis.

Use in serious infections for which less potentially dangerous drugs are ineffective or contraindicated.