Emergent Treatment of Gas Gangrene 

Updated: Feb 12, 2019
Author: Rodolfo D Loureiro, MD; Chief Editor: Jeter (Jay) Pritchard Taylor, III, MD 

Overview

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, 3]

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. 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 80-95% of cases of gas gangrene.[4, 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 and patients who have undergone prior radiation therapy to the abdomen 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.[6]

With C perfringens, the local and systemic manifestations of infection are due to the production of potent extracellular protein toxins by the bacteria. 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 from 1975 estimate 900-1000 cases per year, 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 greater than 25%.

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.[11] 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.[12]

 

Presentation

History

History of gas gangrene is discussed below.[1, 2]

Infection usually results from deep trauma or surgery, although minor procedures, such as intramuscular injection, have been associated with gas gangrene.

The incubation period is usually less than 24 hours but has been described to be anywhere from 7 hours to 6 weeks. When symptoms start, clinical deterioration can occur within hours.

Muscle swelling and severe pain are prominent features. The pain is often out of proportion to physical findings, reflective of the hypoxic state of the muscle tissue, and is key to distinguishing gas gangrene from simple or anaerobic cellulitis.

Systemic toxicity may cause altered mental status, and the progression to toxemia and shock can be rapid.

History of wound contamination with freshwater and seawater should prompt consideration for other causative organisms of necrotizing soft tissue infections, such as Vibrio vulnificus and Aeromonas hydrophila, which have different preferred first-line antibiotic coverage.[13, 14]

Physical

Physical findings of gas gangrene are discussed below.[1, 2, 3, 15, 16, 13, 14, 17] :

Vital signs

Unusually, fever is not a prominent feature of infection and may only be low grade throughout the clinical course. The degree of systemic involvement may produce a spectrum of changes from tachycardia through outright septic shock including hypotension and diaphoresis.

Visual inspection

Initially, the skin may be normal or have mild-to-cellulitic–appearing erythema. Overtime, it typically progresses through a yellowing or bronzing to bulla formation to patches of green/blue/grey/black necrosis. However, discoloration and bullae formation are only present in 20-40% of initial examinations and necrosis is much less frequent. Serosanguineous drainage may be present, described classically as either extremely foul smelling, having a mousy or slightly sweet odor.[18, 13, 14]

Palpation and tissue examination

Most notable is extreme pain of the affected area with or without movement and with palpation. The pain may be out of proportion to the extent of the overlying skin changes. Pain out of proportion to examination may be the only early warning sign distinguishing the necrotizing soft tissue infection from a more benign illness and is present in more than 97% of cases.[14]

Crepitus may be present in 12-25% of cases, but a lack of crepitus on examination does not exclude clostridial myonecrosis. The presence of crepitus is also not specific, as a more common and benign clostridial soft tissue infection, anaerobic cellulitis, may also present with crepitus.[14]

Tense edema may occur and is proportional to the extent of underlying necrosis.

Crepitus, significant discoloration, and tissue tenseness are typically signs of later, more advanced infection and should not be relied upon to diagnose gas gangrene.[14]

Vascular examination

Distal pulses may be normal or diminished depending on the extent of local tissue damage or the presence of compartment syndrome.

Neurologic examination

Decreased pain or anesthesia at the site of infection can indicate that cutaneous nerve endings are being destroyed and that the disease is advanced.

Causes

Risk factors for gas gangrene include the following[9, 19, 20, 21, 22, 18, 13, 17] :

  • Atherosclerosis

  • Battlefield Injury

  • Burns

  • Chronic alcoholism (See the image below.)

    Left lower extremity in a 56-year-old patient with 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.
  • Corticosteroid use

  • Diabetes

  • Gastrointestinal malignancy

  • HIV/AIDS

  • Hypoalbuminemia

  • Intravenous drug abuse (See the image below.)

    A patient developed gas gangrene after injecting c A patient developed gas gangrene after injecting cocaine. Clostridium septicum was isolated in both blood and wound cultures.
  • Malnutrition

  • Mass casualty

  • Obesity

  • Open fractures

  • Peripheral vascular disease

  • Surgery

  • Trauma

Complications

Gas gangrene may progress rapidly; patients often become septic.

 

DDx

Differential Diagnoses

 

Workup

Laboratory Studies

No laboratory findings are completely sensitive or specific for the diagnosis of gas gangrene and, as such, should be used synergistically with a high index of suspicion and thorough clinical examination to guide diagnosis. However, clinically supportive laboratory studies are discussed below.[1, 2, 3, 23, 17]

Gram stain and culture of bullae fluid or wound exudate

Clostridia species are known to be large, gram-positive rods (boxcar appearance); however, the organisms may appear gram variable in Gram stains from tissue samples. The presence of gram-positive or gram-variable rods with few white blood cells is indicative of clostridial etiology, whereas the presence of many white cells is more suggestive of a mixed bacterial infection. Although this information can be helpful, simple superficial wound swabs should not be obtained. Microorganisms that colonize the skin surface often do not contribute to the underlying infection.

C-reactive protein

Though not sensitive or specific for gas gangrene, C-reactive protein values greater than 150 has been associated with an increased risk of soft tissue infection.

Complete blood cell count

CBC count may reveal leukocytosis, bandemia, anemia, thrombocytopenia, and evidence of intravascular hemolysis on smear.

Electrolyte level

Hyperkalemia can result from cell breakdown. Hypocalcemia may result from subcutaneous fat necrosis. Hyponatremia has been shown to occur with increased frequency in necrotizing soft tissue infections.

Liver function tests

Hyperbilirubinemia and liver dysfunction may result from release of toxins. Additionally, transaminitis may occur in the setting of muscle inflammation.

Creatine kinase

Serum creatine kinase and creatine kinase myoglobin elevation may occur from muscle breakdown. However, these findings are neither sensitive nor specific.

Myoglobin level

Myoglobinemia and myoglobinuria can result from muscle breakdown.

Renal panel

Kidney dysfunction may occur secondary to hypotension, hemoglobinuria, and myoglobinuria or direct toxin effect.

Coagulation panel

Coagulopathy and thrombocytopenia can result.

Arterial or venous blood gas determination

Gas gangrene can cause metabolic acidosis with significant lactic acidosis secondary to tissue death and ischemia.

Blood cultures

This may help narrow antibiotic coverage.

Imaging Studies

In the correct clinical context, radiographic evidence of gas in soft tissue is highly suggestive of clostridial myonecrosis. However, gas in the soft tissues is neither sensitive nor specific for gas gangrene. Many different bacteria, trauma, and visceral perforation can cause soft tissue gas. Plain radiographs or ultrasonography can be used to look for the presence of gas. The sensitivity of plain radiographs varies wildly in reports from as low as 20% to as high as 80%. See the images below.

Gas feathering in the arm soft tissue of a patient Gas feathering in the arm soft tissue of a patient with gas gangrene.
Extension of gas gangrene to the chest wall despit Extension of gas gangrene to the chest wall despite initial debridement.

CT scan is more sensitive than plain radiographs for the detection of gas, and it offers the advantage of providing alternative diagnoses (eg, pyomyositis). Studies suggest that the sensitivity and negative predictive value of CT scan for necrotizing soft-tissue infection may be as high as 100%, but a higher index of suspicion is required to order CT scan. Even if a diagnosis is made with clinical acumen or plain radiographs, CT or MRI can still help as a means to evaluate the depth of soft tissue inflammation.[13, 14, 24, 17] However, imaging modalities are not a substitute for surgical exploration.[24, 12, 17]

Other Tests

Once Clostridia are isolated from culture, identification of the lecithinase function of alpha toxin may be elicited by inoculating blood agar with the isolated bacteria. A double area of hemolysis will develop around the colonies, demonstrating the presence of lecithinase. Inoculation of the colonies with anti-toxin will halt the hemolysis.

Procedures

Tissue biopsy with culture and Gram stain is the criterion standard in helping make the diagnosis of gas gangrene.

 

Treatment

Prehospital Care

Prehospital care for gas gangrene includes the following:

  • Oxygenation

  • Intravenous (IV) fluids

Emergency Department Care

Gas gangrene is a true emergency, and concurrent evaluation, treatment, and coordination of care should be carried out.[1, 2, 3, 18]

Generally speaking, the treatment is a combination of antibiotics, surgery, and hyperbaric oxygen. See the following:

  • Airway and breathing: Oxygen and airway management as necessitated by the clinical picture.

  • Circulation: Good vascular access and liberal use of intravenous fluids is indicated. Frequent reassessment of the circulatory status is necessary. If pressors are necessitated, vasoconstrictors should only be used if absolutely necessary; they can decrease perfusion to already ischemic tissue.

  • Administer tetanus toxoid if indicated.

  • Administer antibiotics.

  • Correct electrolyte abnormalities.

  • Check compartment pressures if severe pain and evidence of compartment syndrome are present with minimal cutaneous evidence of infection.

  • Wound care is indicated.

Consultations

Obtain immediate surgical consultation. While laboratory studies and imaging studies may help make the diagnosis of gas gangrene, the criterion standard is tissue biopsy. Furthermore, definitive treatment of gas gangrene is wide debridement of necrotic muscle. Antibiotics will not reach the infected devitalized tissue. Necrotic tissue is identifiable because it does not bleed or contract when debrided.

The presence of hemodynamic instability, crepitus, bullae, subcutaneous gas on imaging, clear tissue necrosis, or any combination of the above is an indication for emergent surgery.[17] The possibility of anaerobic cellulitis should not exclude surgical exploration for necrotic tissue.[13] Patients without these signs are appropriate for monitoring and further workup.

Given the rapidly progressive nature of gas gangrene, multiple episodes of debridement may be required to gain source control of the infection. Loss of limb viability and function are frequent consequences of both infection and debridement, and the need for limb amputation is a relatively common morbidity. The need for amputation is more frequent in gas gangrene than other necrotizing soft tissue infections.[18, 11]

Medical Care

Hyperbaric oxygen therapy

The use of hyperbaric oxygen (HBO) in gas gangrene is controversial, largely owing to a lack of randomized control trials, and should not delay surgical debridement and antibiotic therapy. However, some studies, mostly case reports, have demonstrated decreased morbidity and mortality when HBO is used in supplementation to standard treatments. HBO can also help clarify the demarcation between devitalized and viable tissue, allowing for more conservative excision.[25, 26, 27]  

Prevention

Appropriate wound care at time of injury (eg, debridement of crushed or dead tissue, copious irrigation) may deter infection.

Prophylactic antibiotics may prevent subsequent infection in selected circumstances.

Further Inpatient Care

Urgent-to-emergent surgical debridement is indicated for gas gangrene. Gas gangrene is a rapidly progressive illness. Patients who are initially well-appearing frequently develop the sequelae of severe sepsis or septic shock, and delay to debridement significantly increases this risk.[11, 12]  Admit the patient to an ICU with central access and invasive monitoring as necessary.

Inpatient & Outpatient Medications

Inpatient medications for gas gangrene include intravenous antibiotics and analgesics.

Transfer

Transfer the patient if appropriate surgical specialist and ICU setting are unavailable.

 

Medication

Medication Summary

Antibiotics may not penetrate the ischemic muscle but are important adjuncts to surgery.

Antibiotics

Class Summary

Clostridial species are exquisitely sensitive to a combination of penicillin G and clindamycin. However, because it is difficult initially to distinguish gas gangrene from other soft tissue infections, such as necrotizing fasciitis, which is caused by a broad spectrum of pathogens, empiric first-line antibiotic therapy should be broad.[1, 2, 3, 28] Clindamycin, tetracycline, and other inhibitors of bacterial protein synthesis may, however, have some increased utility as they halt the production of bacterial toxin. Low-level clostridial resistance occurs to clindamycin, and, as such, this agent should not be used as monotherapy.

Antibiotic treatment should include gram-positive (penicillin or cephalosporin), gram-negative (aminoglycoside, third-generation cephalosporin, or ciprofloxacin), and anaerobic coverage (clindamycin or metronidazole). Dual antibiotic therapy is recommended for all necrotizing soft-tissue infections, even in the case of agents (eg, broad-spectrum penicillins) that cover all 3 categories of bacteria given observed synergism in animal models.[13, 14]

In addition, vancomycin or linezolid should be considered in those at risk for methicillin-resistant Staphylococcus aureus (MRSA). Traditional risk factors for MRSA infection are a history of hospitalization, surgery, dialysis, residence in a long-term care facility, presence of a permanent indwelling catheter or percutaneous medical device (eg, tracheostomy tube, gastrostomy tube, Foley catheter), or previous isolation of MRSA. However, in some communities, 8-25% of MRSA infections are now being isolated even in those without risk factors.[1, 2, 3, 28]

Antibiotics should be administered IV since absorption by other routes is inconsistent given the hypotension and suboptimally performing gastrointestinal tract of seriously ill patients.

Tetracycline

Semisynthetic antibacterial agent derived from Streptomyces cultures. Treats gram-positive and gram-negative organisms and mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunit(s).

Penicillin G (Pfizerpen)

DOC for use with infections by clostridial species. Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

Clindamycin (Cleocin)

Lincosamide useful as treatment against serious skin and soft tissue infections caused by most staphylococcal strains. Also effective against aerobic and anaerobic streptococci, except enterococci. Inhibits bacterial protein synthesis by inhibiting peptide chain initiation at bacterial ribosome where it preferentially binds to 50S ribosomal subunit, causing bacterial growth inhibition. Will also halt bacterial production of toxin.

Ceftriaxone (Rocephin)

Third-generation cephalosporin that has broad-spectrum activity against gram-negative organisms, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. Arrests bacterial cell wall synthesis and inhibits bacterial growth by binding to one or more penicillin-binding proteins.

Metronidazole (Flagyl)

Active against various anaerobic bacteria and protozoa. Appears to be absorbed into cells; intermediate-metabolized compounds that are formed bind DNA and inhibit protein synthesis, causing cell death.

Linezolid (Zyvox)

Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. Bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. Used as alternative in patients allergic to vancomycin and for treatment of vancomycin-resistant enterococci.

Gentamicin (Gentacidin, Garamycin)

Aminoglycoside antibiotic used for gram-negative bacterial coverage. Commonly used in combination with an agent with activity against gram-positive organisms and one that covers anaerobes.

Not antibiotic of first choice. Consider using when penicillins or other less toxic drugs are contraindicated, when bacterial susceptibility tests and clinical judgment indicate its use and in mixed infections caused by susceptible strains of staphylococci and gram-negative organisms.

Dosing regimens are numerous and are adjusted based on CrCl and changes in volume of distribution. Gentamicin may be administered IV/IM.

Vancomycin (Vancocin)

Potent antibiotic directed against gram-positive organisms and active against enterococci species. Useful to treat septicemia and skin structure infections. Indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or for those who have infections with resistant staphylococci. For abdominal penetrating injuries, combine with an agent active against enteric flora and/or anaerobes.

To avoid toxicity, assay of vancomycin trough levels after the third dose drawn 0.5 h prior to next dosing currently is recommended. May need to adjust dose in patients diagnosed with renal impairment (use CrCl).

Medicinal gas

Class Summary

The use of hyperbaric oxygen (HBO) in gas gangrene is controversial, largely owing to a lack of randomized control trials, and should not delay surgical debridement and antibiotic therapy. However, some studies, mostly case reports, have demonstrated decreased morbidity and mortality when HBO is used in supplementation to standard treatments. HBO can also help clarify the demarcation between devitalized and viable tissue, allowing for more conservative excision.

Hyperbaric oxygen (HBO)

HBO produces a tissue level of 300 mm Hg of oxygen. This is approximately 50 mm Hg greater than the partial pressure necessary to induce bacteriostasis and halt toxin production. Potential benefits include improved neutrophil-mediated killing of bacteria, direct bactericidal effect on anaerobes, improved activity of some antibiotics, and enhanced wound healing. Given its aerotolerance, gas gangrene caused by C septicum may be less amenable to HBO therapy.

Toxoids

Class Summary

Toxoids are used to induce active immunity.

Tetanus toxoid adsorbed or fluid

Used to induce active immunity against tetanus in selected patients. Immunizing agents of choice for most adults and children >7 y are tetanus and diphtheria toxoids. Necessary to administer booster doses to maintain tetanus immunity throughout life.

Pregnant patients should receive only tetanus toxoid not a diphtheria antigen-containing product.

In children and adults, may administer into deltoid or midlateral thigh muscles. In infants, preferred site of administration is mid thigh laterally.

Immunoglobulins

Class Summary

Immunoglobulins are used to induce passive immunity.

Tetanus immune globulin (TIG)

Used for passive immunization of any person with a wound that may be contaminated with tetanus spores.

Analgesics

Class Summary

Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who have sustained trauma or have sustained injuries.

Morphine sulfate (Astramorph, MS Contin, MSIR, Oramorph)

DOC for analgesia due to reliable and predictable effects, safety profile, and ease of reversibility with naloxone.

Various IV doses are used; commonly titrated until desired effect obtained.

Fentanyl citrate (Duragesic, Sublimaze)

A synthetic opioid that is 75-200 times more potent and has a much shorter half-life than morphine sulfate. Has less hypotensive effects and is safer in patients with hyperactive airway disease than morphine because of minimal-to-no associated histamine release. By itself, it causes little cardiovascular compromise, although addition of benzodiazepines or other sedatives may result in decreased cardiac output and blood pressure.

Highly lipophilic and protein-bound. Prolonged exposure leads to accumulation in fat and delays weaning process.

Consider continuous infusion because of the short half-life of fentanyl.

Parenteral form is DOC for conscious sedation analgesia. Ideal for analgesic action of short duration during anesthesia and immediate postoperative period.

Excellent choice for pain management and sedation with short duration (30-60 min) and easy to titrate. Easily and quickly reversed by naloxone.

After initial parenteral dose, subsequent parenteral doses should not be titrated more frequently than q3h or q6h thereafter.

Transdermal form is used only for chronic pain conditions in patients with tolerance to opioids. When using transdermal dosage form, most patients are controlled with 72-h dosing intervals; however, some patients require dosing intervals of 48 h.

Easily and quickly reversed by naloxone.