Over the past century, much has been learned about the pathogenesis of this disease, and novel therapies are on the horizon for patients with this devastating infection. Clostridium perfringens is a gram-positive, spore-forming, nonmotile, rod-shaped organism commonly found in soil and in the intestines of humans and other animals. The species has been divided into 5 distinct types, A—E. Of these subgroups, C. Although classified as an anaerobe, C. Under optimal conditions, its generation time can be as little as 8—10 min, and growth is accompanied by abundant gas production.
Gas gangrene caused by C. PLC's role as the major lethal factor in C. Both active and passive immunization of animals against PLC or its C-terminal fragment are protective in experimental wild-type infections.
Similarly, experimental infections established with genetic mutants of C. The importance of PFO in the pathogenesis of gas gangrene has been largely controversial, despite the early knowledge of its hemolytic nature and its serological and antigenic relationships to the cholesterol-binding cytolysins from Streptococcus pyogenes, Streptococcus pneumoniae , and Listeria monocytogenes. Recently, the amino acid and nucleotide sequences of pneumolysin, streptolysin O, and PFO have been determined [ 3—6 ].
Impressive homology exists among the amino acid sequences of these toxins, particularly in the region that contains the cysteine residue near the amino terminus, where a highly conserved segment of 12 amino acids is identical for all 3 toxins. Some of these toxins, including PFO, have been shown to facilitate the growth of their respective organisms within mammalian phagocytic cells.
Furthermore, experimental animal studies have demonstrated the protective efficacy of several antibody preparations against these toxins [ 1 ]. Thus, these studies support a principal role for thiol-activated cytolysins in the pathogenesis of their respective diseases.
PLC and PFO each contribute to the morbidity and morality of gas gangrene by uniquely different mechanisms, which are detailed in the following sections. PLC is hemolytic, is cytotoxic to platelets and leukocytes, and increases capillary permeability—effects that are likely related to its ability to cleave sphingomyelin and the phosphoglycerides of choline, ethanolamine, and serine present in eukaryotic cell membranes.
PLC requires calcium for optimal activity. Histidine residues have been shown to be essential for the binding of zinc ions. Basak et al. Titball et al. Hemodynamic collapse is a common occurrence in patients with gas gangrene caused by C. For example, a prompt reduction in cardiac index CI occurred in rabbits that received either PLC or a crude toxin preparation [ 9 ] figure 1.
As reflected by the increased mortality in the rabbits that received rPLC and crude toxin, a greater reduction in CI was also measured in these groups compared with those that received recombinant PFO rPFO or normal saline [ 9 ]. Similarly, a marked decline in mean arterial pressure MAP was observed in rabbits treated with rPLC and crude toxin, although these effects were delayed until the later stages of the experiment figure 2 [ 9 ]. Thus, rabbits that received PLC-containing toxin preparations maintained MAP in the face of a falling CI by as-yet-uncharacterized compensatory mechanism for a brief period before hypotension ultimately occurred.
The physiological mechanisms that maintained MAP did not include significant changes in heart rate or central venous pressure until the terminal stages of the experiments, if at all [ 9 ]. Effects of clostridial exotoxins on cardiac index CI. CI was measured over a 3-h period by thermodilution. Data adapted from Asmuth et al. Effects of clostridial exotoxins on mean arterial pressure.
Mean arterial pressure was monitored continuously for 3 h via a catheter placed in the carotid artery. Of interest, rabbits that received crude toxin containing both PLC and PFO activity demonstrated peripheral vascular resistance PVR values intermediary to the other toxin groups. In total, these experiments suggest that PLC initially augments cardiac function, counteracting the vasodilatory effect of rPFO.
Later, decreased cardiac output, hypotension, and death occurred. In addition, PLC may contribute indirectly to shock by stimulating production of endogenous mediators such as TNF [ 11 ] figure 3 and platelet-activating factor [ 12 ]. Samples were collected at 24 h and assayed in duplicate by commercial enzyme-linked immunosorbent assay.
From Stevens and Bryant [ 11 ]. Perhaps PFO-induced synthesis of nitric oxide by host cells such as macrophages or endothelial cells could also play a role in early hypotension. This latter point should be considered when interpreting results from experiments that have used isogenic mutants or single toxins. Thus, shock associated with gas gangrene may be attributable, in part, to direct and indirect effects of toxins. PLC directly suppresses myocardial contractility [ 10 ], thereby contributing to profound hypotension via a sudden reduction in cardiac output [ 9 ].
PFO reduces systemic vascular resistance and markedly increases cardiac output [ 9 , 10 ]. PFO-induced after-load reduction occurs undoubtedly through the induction of endogenous mediators that cause relaxation of blood vessel wall tension [ 15 ]. The edges of the infected area grow so quickly that changes can be seen over minutes.
The area may be completely destroyed. If the condition is not treated, the person can go into shock with decreased blood pressure hypotension , kidney failure , coma, and finally death. Surgical removal amputation of an arm or leg may be needed to control the spread of infection. Amputation sometimes must be done before all test results are available.
Antibiotics are also given. These medicines are given through a vein intravenously. Pain medicines may also be prescribed. Call your provider if you have signs of infection around a skin wound.
Go to the emergency room or call the local emergency number such as , if you have symptoms of gas gangrene. Clean any skin injury thoroughly. Watch for signs of infection such as redness, pain, drainage, or swelling around a wound.
See your provider promptly if these occur. The best way to prevent gas gangrene is to practice proper hygiene. If you have an injury, make sure to clean the skin thoroughly and to cover the wound with a bandage. Contact your doctor at the first signs of infection. Signs of infection include redness, swelling, pain, and discharge. Your doctor will remove any foreign objects and dead tissue from the wound.
This will help lower your risk of developing an infection. Making certain lifestyle changes can also help reduce your risk for gas gangrene. These include:. Gangrene is when part of your body tissue dies. Though it usually affects your extremities, like your toes and fingers, it can also affect your…. Boils are caused by bacteria building up in a hair follicle and pushing up to the surface of the skin.
Recurring boils happen for a number of reasons…. Certain E. Learn about other bacteria and parasites like pinworms and how to prevent…. Shigellosis is a bacterial infection that affects the digestive system. The Shigella bacterium is spread through contact with contaminated feces. As a boil on the skin matures, it typically develops a visible core of pus.
Learn when to see a doctor, how to get the core out of a boil at home, and…. Q fever, also called query fever, is a bacterial infection caused by bacteria commonly found in cattle, sheep, and goats. Humans typically get Q fever…. A doctor typically orders a sputum stain to determine if a person has tuberculosis TB or another type of mycobacterial infection. Symptoms suggest the diagnosis, and imaging tests or culture of a sample taken from infected tissue is usually done.
Gas gangrene is a fast-spreading clostridial infection of muscle tissue that, if untreated, quickly leads to death. Clostridia Overview of Clostridial Infections Clostridia are bacteria that commonly reside in the intestine of healthy adults and newborns.
Clostridia also reside in animals, soil, and decaying vegetation. These bacteria do not require That is, they are anaerobes Overview of Anaerobic Bacteria Bacteria can be classified in several different ways. One way is based on their need for oxygen—whether they need oxygen to live and grow: Aerobes: Those that need oxygen Anaerobes: Those that So they reproduce well in soft tissues that have been severely damaged and in wounds that are very deep.
Such tissues have poor blood flow and thus low oxygen levels. Most clostridial soft-tissue infections, including gangrene, are caused by Clostridium perfringens. Clostridial soft-tissue infections usually develop hours or days after an injury but sometimes take several days to appear.
Shallow skin infections cellulitis Cellulitis Cellulitis is a spreading bacterial infection of the skin and the tissues immediately beneath the skin. This infection is most often caused by streptococci or staphylococci. Redness, pain, and Deeper infections into fibrous tissue around the muscles called fascia fasciitis or muscle myositis , which usually are painful. Sometimes the bacteria in soft tissues produce large amounts of gas as a waste product.
The gas can form bubbles and blisters in tissue. Often, the infection blocks small blood vessels. As a result, the infected tissue dies, leading to gangrene. The dead tissue enables the clostridial infection to spread even faster.
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