Gas gangrene

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Gas gangrene
Other namesMyonecrosis,[ clarification needed ] clostridial myonecrosis
Gas gangrene.jpg
Photograph before right leg amputation (hemipelvectomy) of a patient with gas gangrene. The right thigh is edematous (swollen) and discoloured with necrotic bullae (large blisters). Crepitation is detected on deep palpation. At this juncture, the patient is in shock, and died less than eight hours later.
Specialty Infectious disease

Gas gangrene (also known as clostridial myonecrosis [1] ) is a bacterial infection that produces tissue gas in gangrene. This deadly form of gangrene usually is caused by Clostridium perfringens bacteria. About 1,000 cases of gas gangrene are reported yearly in the United States. [2]

Contents

Myonecrosis is a condition of necrotic damage, specific to muscle tissue. It is often seen in infections with C. perfringens or any of myriad soil-borne anaerobic bacteria. Bacteria cause myonecrosis by specific exotoxins. These microorganisms are opportunistic and, in general, enter the body through significant skin breakage. Gangrenous infection by soil-borne bacteria was common in the combat injuries of soldiers well into the 20th century, because of non-sterile field surgery and the basic nature of care for severe projectile wounds. [3]

Other causes of myonecrosis include envenomation by snakes of the genus Bothrops (family Viperidae), ischemic necrosis, caused by vascular blockage (e.g., diabetes type II), tumours that block or hoard blood supply, and disseminated intravascular coagulation or other thromboses.

Presentation

Macroscopic and microscopic findings from a patient who died from intestinal (bowel) gas gangrene (a) Macroscopic picture of the edematous intestinal wall with multiple submucosal and subserosal cysts (b) Histological picture of the intestinal mucosa with nonreactive necrosis (c) Gram stain of cysts with large, rod-shaped bacteria (d) Electron microscopic picture of a bacterium found in a submucosal cyst Pneumatosis coli gas gangrene.jpg
Macroscopic and microscopic findings from a patient who died from intestinal (bowel) gas gangrene
(a) Macroscopic picture of the edematous intestinal wall with multiple submucosal and subserosal cysts
(b) Histological picture of the intestinal mucosa with nonreactive necrosis
(c) Gram stain of cysts with large, rod-shaped bacteria
(d) Electron microscopic picture of a bacterium found in a submucosal cyst
Plain X-Ray of a patient with gas gangrene of left leg Gas Gangrene in XRay.jpg
Plain X-Ray of a patient with gas gangrene of left leg

Gas gangrene can cause myonecrosis (muscle tissue death), gas production, and sepsis. Progression to toxemia and shock is often very rapid. It can easily be noticed by the large, blackened sores that form, as well as a degree of loud and distinctive crepitus caused by gas escaping the necrotic tissue.[ citation needed ]

Symptoms

A multitude of symptoms is associated with gas gangrene. Distinctively, black lesions on the skin appear in a bubble form which allows visualization of gas-producing bacteria. Symptoms include: [4]

Etiology

Clostridium species produce more toxins and exhibit higher degrees of virulence than any other bacterial taxon. [5] Clostridium infections are usually opportunistic, and occur in individuals with serious preexisting medical conditions. However, Clostridium infections are also known to occur in healthy individuals. Four species of Clostridium ( Clostridium botulinum , Clostridium perfringens , Clostridium tetani , and Clostridium sordelli ) are responsible for most human infections. Since Clostridium is an obligate anaerobe taxon, the bacterium infects hypoxic tissues, which have become anaerobic due to restricted blood flow, degradation of blood vessels, or atherosclerosis. Immunocompromised individuals exhibit higher susceptibility for infection and higher mortality rates.[ citation needed ]

Virulence factors

Members of the Clostridium genus exhibit a plethora of virulence factors. Common virulence factors associated with gas gangrene include alpha toxin and theta toxin. C. perfringens causes 80–90% of infections and produces both these toxins.[ citation needed ]

Alpha toxin (α-toxin)

C. perfringens alpha toxin is widely associated with gas gangrene as it is its main virulence factor whilst invading its host. Alpha toxin is associated with hemolysis, thus restricting blood flow towards the area of infection. As the surrounding circulatory system collapses, neutrophils and monocytes, eosinophils and basophils cannot reach target areas of infection. The hemolytic activity of alpha toxin produces an anaerobic environment essential for the proliferation of the bacteria. Alpha toxin also exhibits the ability to infiltrate surrounding cellular tissue and cause a cascade of aberrant biochemical activity.[ citation needed ]

Theta toxin (Θ-toxin)

Theta toxin is also employed by C. perfringens as a virulence factor. Theta toxin also promotes vascular degradation as does its counterpart alpha toxin. A platelet-activation factor is employed which triggers an acute inflammatory response in nearby tissues. [6] This inflammatory response leads to constriction of surrounding arteries and promotes an anaerobic environment for C. perfringens growth and pathophysiology.[ citation needed ]

Beta toxin (β-toxin)

Beta toxin is an integral virulence factor in promoting enterocolitis and enterotoxemia. [7] This toxin uses pores in the cellular biolipid membrane to import a pathogenic factor into organisms.[ citation needed ]

Pathophysiology

Gas gangrene is caused by exotoxin-producing Clostridium species (most often C. perfringens , and C. novyi , [8] [9] but less commonly C. septicum [10] or C. ramnosum ), [11] which are mostly found in soil, but also found as normal gut flora, and other anaerobes (e.g., Bacteroides and anaerobic streptococci).[ citation needed ]

Bacterium of the Clostridial species produce two toxins: alpha and theta toxins, which cause necrotizing damage to tissues. [12]

Other organisms may occasionally cause gas gangrene (for example, Klebsiella pneumoniae in the context of diabetes). [13]

A gas composition of 5.9% hydrogen, 3.4% carbon dioxide, 74.5% nitrogen, and 16.1% oxygen was reported in one clinical case. [14]

Myonecrosis differs slightly from other types of necrosis. While the underlying causes are almost identical, the type of affected tissue (in particular, muscle tissue) is significantly more important for the patient's general health. Superficial necrosis is unsightly and can lead to unattractive scarring, but otherwise does not affect the patient's likelihood of survival or physical capability to the same extent. However, massive myonecrosis will likely result in the loss of movement of the entire region. If the necrotic damage is allowed to continue throughout an affected limb, then often that entire limb is lost permanently.[ citation needed ]

It is often difficult to identify the extent of muscle damage, as C. perfringens may be at work in deeper fascial layers below the skin. Unlike other anaerobic infections, discharge in these infections is often not purulent (filled with pus). Instead, the discharge is often described as "sweetly putrid" or "dishwater pus" because it is much thinner than normal pus. This is due to the lysis of neutrophils, a type of white blood cell, caused by the lecithinases and other toxins released by Clostridium species. [15]

Soil-borne anaerobes are particularly well-adapted to surviving harsh conditions. Often, a scarcity of nutrition and competition for resources from numerous other species occurs. Changes in pH and temperature are often significant, also. Bacteria often possess the ability to create exotoxins to assist them in competing with other microbes in their natural environments. When such bacteria are able to enter a living host, they encounter a vast supply of nutrients, warm conditions, and an abundance of water. This enables the microbes to rapidly proliferate, far in excess of the immune system's capability to defend, as prokaryotic bacteria possess a far greater capacity for multiplication than the host's immune system. The combination of bacterial load and ability to multiply is the basis for the microbes' ability to cause massive infection. Alongside such rapid proliferation is a corresponding mass-production of exotoxin that causes severe damage to local tissue in the host. One such exotoxin is alpha toxin, which is produced by C. perfringens and is the key virulence factor in its pathogenesis. [16]

Massive infection, gross injury, and depletion of the host's immune capability result in system-wide sepsis. This is partly due to the burden on the immune system, its corresponding release of inflammatory cytokines, and the distribution of bacterial toxins. Massive infection is likely to result in death from a combination of system-wide septic shock and the unintentionally damaging effects of the immune response. In animals, disability and distress caused by all of these factors markedly increase the chance of predation.[ citation needed ]

Diagnosis

Various diagnostic methods can be employed in the diagnosis of Gas gangrene. Due to low incidence of myonecrosis it is an easy-to-overlook diagnosis. As bacterial infections mostly exhibit the same symptoms, early diagnosis of gas gangrene rarely occurs. The ambiguous symptoms only contribute to a poorer prognosis. Diagnostic methods include: [15]

Treatment

Treatment is usually debridement and excision, with amputation necessary in many cases. Water-soluble antibiotics (such as penicillin) alone are not effective because they do not penetrate ischaemic muscles sufficiently to be effective. Penicillin is effective against C. perfringens. When gas gangrene occurs in such regions as the abdominal cavity, the patient can be treated in a hyperbaric chamber, which contains a pressurized oxygen-rich atmosphere. The oxygen saturates the infected tissues and thereby prevents the growth of the obligately anaerobic clostridia. [17] The growth of C. perfringens is inhibited when the availability of oxygen is equivalent to a partial pressure of around 9–10 kPa (compare to 4–5 kPa in venous blood under normal conditions, with 11–13 kPa in arteries and 21 kPa in air at sea level), so if the treatment is started early, this condition can mostly be cured. [18]

Prognosis

Gas gangrene left untreated is a potentially fatal infection. Early diagnosis of the type of infection and species causing the infection will improve prognosis tremendously. Preventive measures are employed universally through medical facilities to stymie bacterial infections in patients. Reducing the susceptibility of infection will promote a better prognosis by practicing good hygiene and preventing the contraction of diseases which produce hypoxia or an immunocompromised state.[ citation needed ]

Following resolution of myonecrosis, patients will often require further care following the deleterious effects caused by the infection. Skin grafts are often required following removal of necrotic tissues. Former patients will still require hyperbaric oxygen therapy to prevent a recurring infection. [19]

Epidemiology

Clostridium species are found in abundance in soil, especially soil used for animal husbandry. [5] In medical facilities, it thrives when unhygienic circumstances prevail. In the United States, the incidence of myonecrosis is only about 1,000 cases per year. [20]

During World War I and World War II, Clostridial myonecrosis was found in 5% of wounds, but with improvement in wound care, antisepsis and the use of antibiotics, the incidence had fallen to 0.1% of war-related wound infections by the Vietnam War. [20]

With the best of care—including early recognition, surgical care, antibiotic treatment, and hyperbaric oxygen therapy—the mortality rate is 20-30% and can be as low as 5-10%. If untreated, the disease has a 100% fatality rate. [20]

Additional images

See also

Related Research Articles

<span class="mw-page-title-main">Necrosis</span> Unprogrammed cell death caused by external cell injury

Necrosis is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who is often regarded as one of the founders of modern pathology. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated digestion of cell components. In contrast, apoptosis is a naturally occurring programmed and targeted cause of cellular death. While apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental and can be fatal.

<span class="mw-page-title-main">Gangrene</span> Type of tissue death by a lack of blood supply

Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the gangrene is caused by an infectious agent, it may present with a fever or sepsis.

<span class="mw-page-title-main">Necrotizing fasciitis</span> Infection that results in the death of the bodys soft tissue

Necrotizing fasciitis (NF), also known as flesh-eating disease, is a bacterial infection that results in the death of parts of the body's soft tissue. It is a severe disease of sudden onset that spreads rapidly. Symptoms usually include red or purple skin in the affected area, severe pain, fever, and vomiting. The most commonly affected areas are the limbs and perineum.

<i>Clostridium</i> Genus of Gram-positive bacteria, which includes several significant human pathogens

Clostridium is a genus of anaerobic, Gram-positive bacteria. Species of Clostridium inhabit soils and the intestinal tract of animals, including humans. This genus includes several significant human pathogens, including the causative agents of botulism and tetanus. It also formerly included an important cause of diarrhea, Clostridioides difficile, which was reclassified into the Clostridioides genus in 2016.

<i>Clostridium perfringens</i> Species of bacterium

Clostridium perfringens is a Gram-positive, bacillus (rod-shaped), anaerobic, spore-forming pathogenic bacterium of the genus Clostridium. C. perfringens is ever-present in nature and can be found as a normal component of decaying vegetation, marine sediment, the intestinal tract of humans and other vertebrates, insects, and soil. It has the shortest reported generation time of any organism at 6.3 minutes in thioglycolate medium.

<span class="mw-page-title-main">Exotoxin</span> Toxin from bacteria that destroys or disrupts cells

An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface.

<span class="mw-page-title-main">Clostridia</span> Class of bacteria

The Clostridia are a highly polyphyletic class of Bacillota, including Clostridium and other similar genera. They are distinguished from the Bacilli by lacking aerobic respiration. They are obligate anaerobes and oxygen is toxic to them. Species of the class Clostridia are often but not always Gram-positive and have the ability to form spores. Studies show they are not a monophyletic group, and their relationships are not entirely certain. Currently, most are placed in a single order called Clostridiales, but this is not a natural group and is likely to be redefined in the future.

<span class="mw-page-title-main">Blackleg (disease)</span> Bacterial disease of animals

Blackleg, black quarter, quarter evil, or quarter ill is an infectious bacterial disease most commonly caused by Clostridium chauvoei, a Gram-positive bacterial species. It is seen in livestock all over the world, usually affecting cattle, sheep, and goats. It has been seen occasionally in farmed bison and deer. The acute nature of the disease makes successful treatment difficult, and the efficacy of the commonly used vaccine is disputed.

Virulence factors are cellular structures, molecules and regulatory systems that enable microbial pathogens to achieve the following:

<span class="mw-page-title-main">Fournier gangrene</span> Medical condition

Fournier gangrene is a type of necrotizing fasciitis or gangrene affecting the external genitalia or perineum. It commonly occurs in older men, but it can also occur in women and children. It is more likely to occur in people with diabetes or alcoholism or those who are immunocompromised.

<i>Clostridium perfringens</i> alpha toxin Toxin produced by the bacterium Clostridium perfringens

Clostridium perfringens alpha toxin is a toxin produced by the bacterium Clostridium perfringens and is responsible for gas gangrene and myonecrosis in infected tissues. The toxin also possesses hemolytic activity.

<i>Clostridium septicum</i> Species of bacterium

Clostridium septicum is a gram positive, spore forming, obligate anaerobic bacterium.

<span class="mw-page-title-main">Clostridium enterotoxin</span>

Clostridium enterotoxins are toxins produced by Clostridium species. Clostridial species are one of the major causes of food poisoning/gastrointestinal illnesses. They are anaerobic, gram-positive, spore-forming rods that occur naturally in the soil. Among the family are: Clostridium botulinum, which produces one of the most potent toxins in existence; Clostridium tetani, causative agent of tetanus; and Clostridium perfringens, commonly found in wound infections and diarrhea cases.

<span class="mw-page-title-main">AB toxin</span>

The AB toxins are two-component protein complexes secreted by a number of pathogenic bacteria, though there is a pore-forming AB toxin found in the eggs of a snail. They can be classified as Type III toxins because they interfere with internal cell function. They are named AB toxins due to their components: the "A" component is usually the "active" portion, and the "B" component is usually the "binding" portion. The "A" subunit possesses enzyme activity, and is transferred to the host cell following a conformational change in the membrane-bound transport "B" subunit. These proteins consist of two independent polypeptides, which correspond to the A/B subunit moieties. The enzyme component (A) enters the cell through endosomes produced by the oligomeric binding/translocation protein (B), and prevents actin polymerisation through ADP-ribosylation of monomeric G-actin.

Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by Clostridium botulinum and less frequently by other Clostridium species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxins. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.

Clostridium novyi (oedematiens) a Gram-positive, endospore- forming, obligate anaerobic bacteria of the class Clostridia. It is ubiquitous, being found in the soil and faeces. It is pathogenic, causing a wide variety of diseases in man and animals.

Hathewaya histolytica is a species of bacteria found in feces and the soil. It is a motile, gram-positive, aerotolerant anaerobe. H. histolytica is pathogenic in many species, including guinea pigs, mice, and rabbits, and humans. H. histolytica has been shown to cause gas gangrene, often in association with other bacteria species.

Clostridium cadaveris is an enteric, gas-forming, motile, strictly anaerobic gram-positive bacterium of the genus Clostridium. First described by Klein in 1899, it was noted to be the most prominent bacteria during human decomposition; historically it was described as "putrefying flora".

Anaerobic infections are caused by anaerobic bacteria. Obligately anaerobic bacteria do not grow on solid media in room air ; facultatively anaerobic bacteria can grow in the presence or absence of air. Microaerophilic bacteria do not grow at all aerobically or grow poorly, but grow better under 10% carbon dioxide or anaerobically. Anaerobic bacteria can be divided into strict anaerobes that can not grow in the presence of more than 0.5% oxygen and moderate anaerobic bacteria that are able of growing between 2 and 8% oxygen. Anaerobic bacteria usually do not possess catalase, but some can generate superoxide dismutase which protects them from oxygen.

The thiol-activated Cholesterol-dependent Cytolysin(CDC) family is a member of the MACPF superfamily. Cholesterol dependent cytolysins are a family of β-barrel pore-forming exotoxins that are secreted by gram-positive bacteria. CDCs are secreted as water-soluble monomers of 50-70 kDa, that when bound to the target cell, form a circular homo-oligomeric complex containing as many as 40 monomers. Through multiple conformational changes, the β-barrel transmembrane structure is formed and inserted into the target cell membrane. The presence of cholesterol in the target membrane is required for pore formation, though the presence of cholesterol is not required by all CDCs for binding. For example, intermedilysin secreted by Streptococcus intermedius will bind only to target membranes containing a specific protein receptor, independent of the presence of cholesterol, but cholesterol is required by intermedilysin for pore formation. While the lipid environment of cholesterol in the membrane can affect toxin binding, the exact molecular mechanism that cholesterol regulates the cytolytic activity of the CDC is not fully understood.

References

  1. ↑ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology . Saunders Elsevier. p.  269. ISBN   978-0-7216-2921-6.
  2. ↑ Jerrold B. Leikin; Frank P. Paloucek, eds. (2008), "Clostridium perfringens Poisoning", Poisoning and Toxicology Handbook (4th ed.), Informa, pp. 892–893, ISBN   978-1-4200-4479-9
  3. ↑ Pailler JL, Labeeu F (1986). "La gangrène gazeuse: une affection militaire?" [Gas gangrene: a military disease?]. Acta Chir. Belg. (in French). 86 (2): 63–71. PMID   3716723.
  4. ↑ "Gas gangrene". www.amboss.com. Retrieved 2021-03-25.
  5. 1 2 Bryant, Amy E.; Stevens, Dennis L. "179: Gas Gangrene and Other Clostridial Infections". Harrison's Principles of Internal Medicine (19th ed.). Retrieved 1 May 2020.
  6. ↑ Stevens DL, Bryant AE (June 1993). "Role of theta toxin, a sulfhydryl-activated cytolysin, in the pathogenesis of clostridial gas gangrene". Clin. Infect. Dis. 16 (Suppl 4): S195–S199. doi:10.1093/clinids/16.supplement_4.s195. PMID   8324118.
  7. ↑ Masahiro, Nagahama; Sadayuki, Ochi; Masataka, Oda; Kazuaki, Miyamoto; Keiko, Kobayashi (February 3, 2015). "Recent Insights into Clostridium perfringens Beta-Toxin". Toxins (Basel). 7 (2): 396–406. doi: 10.3390/toxins7020396 . PMC   4344631 . PMID   25654787.
  8. ↑ Hatheway CL (January 1990). "Toxigenic clostridia". Clin. Microbiol. Rev. 3 (1): 66–98. doi:10.1128/CMR.3.1.66. PMC   358141 . PMID   2404569.
  9. ↑ Busch, Christian; Schömig, Kathrin; Hofmann, Fred; Aktories, Klaus (November 2000). "Characterization of the Catalytic Domain of Clostridium novyi Alpha-Toxin". Infection and Immunity . 68 (11): 6378–6383. doi:10.1128/iai.68.11.6378-6383.2000. PMC   97722 . PMID   11035748.
  10. ↑ Bratton SL, Krane EJ, Park JR, Burchette S (1992). "Clostridium septicum infections in children". Pediatr Infect Dis J. 11 (7): 569–75. doi:10.1097/00006454-199207000-00011. PMID   1528648. S2CID   40705266.
  11. ↑ van der Vorm ER, von Rosenstiel IA, Spanjaard L, Dankert J (April 1999). "Gas gangrene in an immunocompromised girl due to a Clostridium ramosum infection". Clin. Infect. Dis. 28 (4): 923–4. doi: 10.1086/517249 . PMID   10825071.
  12. ↑ Buboltz, Jerome B.; Murphy-Lavoie, Heather M. (October 13, 2019). Gas Gangrene. PMID   30725715 . Retrieved 1 May 2020.
  13. ↑ Chang CW, Wang TE, Shih SC, Chang WH, Chen MJ (2008). "Shortness of breath, fever—and pain in both legs". Lancet. 372 (9648): 1518. doi:10.1016/S0140-6736(08)61621-9. PMID   18970978. S2CID   12559431.
  14. ↑ ^ Chi CH, Chen KW, Huang JJ, Chuang YC, Wu MH (1995). "Gas composition in Clostridium septicum gas gangrene". J Formos Med Assoc. 94 (12): 757–9. PMID   8541740.
  15. 1 2 "Gas Gangrene". The Lecturio Medical Concept Library. Retrieved 22 July 2021.
  16. ↑ Awad MM, Bryant AE, Stevens DL, Rood JI (January 1995). "Virulence studies on chromosomal alpha-toxin and theta-toxin mutants constructed by allelic exchange provide genetic evidence for the essential role of alpha-toxin in Clostridium perfringens-mediated gas gangrene". Mol. Microbiol. 15 (2): 191–202. doi:10.1111/j.1365-2958.1995.tb02234.x. PMID   7746141. S2CID   12440686.
  17. ↑ Gerard J. Tortora; Berdell R. Funke; Christine L. Case (2010), Microbiology: An Introduction (10th ed.), Benjamin Cummings, p. 646, ISBN   978-0-321-55007-1
  18. ↑ Guyton and Hall. Textbook of Medical Physiology, 12th edition, chapter 44, "Physiological issues in deep-sea diving and other high-pressure conditions"
  19. ↑ Buboltz JB, Murphy-Lavoie HM (October 13, 2019). "Gas Gangrene". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID   30725715 . Retrieved 1 May 2020.
  20. 1 2 3 Buboltz, J. B.; Murphy-Lavoie, H. M. (2021). "Gas Gangrene". StatPearls. StatPearls. PMID   30725715.
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