Chapter 135. Gas Gangrene and Other Clostridial Infections (Part 1)

Harrisons Internal Medicine Chapter 135. Gas Gangrene and Other Clostridial InfectionsDefinition Bacteria of the genus Clostridium are gram-positive, spore-forming, obligate anaerobes that are ubiquitous in nature. There are 60 recognized species of clostridia, many of which are generally considered saprophytic. Some of these species are pathogenic for humans and animals, particularly under conditions of lowered oxidation-reduction potential. Infections associated with these organisms range from localized wound contamination to overwhelming systemic disease. The four major disease categories for which clostridia are responsible are intestinal disorders, suppurative deep-tissue infections, skin and soft tissue infections, andbacteremia. Toxins play a major role...
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Chapter 135. Gas Gangrene and Other Clostridial Infections (Part 1) Chapter 135. Gas Gangrene and Other Clostridial Infections (Part 1) Harrisons Internal Medicine > Chapter 135. Gas Gangrene and OtherClostridial Infections Definition Bacteria of the genus Clostridium are gram-positive, spore-forming,obligate anaerobes that are ubiquitous in nature. There are >60 recognized speciesof clostridia, many of which are generally considered saprophytic. Some of thesespecies are pathogenic for humans and animals, particularly under conditions oflowered oxidation-reduction potential. Infections associated with these organismsrange from localized wound contamination to overwhelming systemic disease. Thefour major disease categories for which clostridia are responsible are intestinaldisorders, suppurative deep-tissue infections, skin and soft tissue infections, andbacteremia. Toxins play a major role in some of these syndromes. Colitis causedby C. difficile is discussed in Chap. 123. Etiology In humans, clostridia normally reside in the gastrointestinal tract and in thefemale genital tract, although they occasionally are isolated from the skin or themouth. Of the known clostridial species, at least 30 have been isolated fromhuman infections. Like several other pathogenic anaerobic bacterial species,clostridia are quite aerotolerant, but they do not grow on artificial media in thepresence of oxygen. Clostridia characteristically produce abundant gas in artificialmedia and form subterminal endospores. C. perfringens, one of the most clinicallyimportant species, is encapsulated and nonmotile and rarely sporulates in artificialmedia; the spores can usually be destroyed by boiling. C. tetani and C. botulinumare discussed in detail in Chaps. 133 and 134, respectively. Clostridia are present in the normal colonic flora at concentrations of 109–1010/g. Of the ≥30 species that normally colonize humans, C. ramosum is the mostabundant and is followed in frequency by C. perfringens. These organisms areuniversally present in soil at concentrations of up to 10 4/g. C. perfringens strainsare classified (on the basis of their production of several lethal toxins) into fivetypes, designated A through E. Type A predominates in fecal flora of humans aswell as in soil, whereas the habitats of types B through E are thought to be theintestinal tracts of other animals. Although clostridia are gram-positive organisms,many species may appear to be gram-negative in clinical specimens or stationary-phase cultures. Therefore, the results of Grams staining of cultures or clinicalmaterial should be interpreted with great care. C. perfringens is the most common of the clostridial species isolated fromtissue infections and bacteremias; next in frequency are C. novyi and C. septicum.In the category of enteric infections, C. difficile is an important cause of antibiotic-associated colitis, and C. perfringens is associated with food poisoning (type A)and enteritis necroticans (type C). Pathogenesis Despite the isolation of clostridial species from many serious traumaticwounds, the prevalence of severe infections due to these organisms is low. Twofactors that appear to be essential to the development of severe disease are tissuenecrosis and a low oxidation-reduction potential. C. perfringens requires ~14amino acids and at least 6 additional growth factors for optimal growth. Thesenutrients are not found in appreciable concentrations in normal body fluids but arepresent in necrotic tissue. When C. perfringens grows in necrotic tissue, a zone oftissue damage due to the toxins elaborated by the organism allows progressivegrowth. In contrast, when only a few bacteria leak into the bloodstream from asmall defect in the intestinal wall, the organisms do not have the opportunity tomultiply rapidly because blood as a medium for growth is relatively deficient incertain amino acids and growth factors. Therefore, in a patient without tissuenecrosis, bacteremia is usually benign. C. perfringens possesses at least 17 possible virulence factors, including 12active tissue toxins and enterotoxins. The enterotoxins include four major lethaltoxins: α, β, ε, and 1. The α toxin is a phospholipase C (lecithinase) that splitslecithin into phosphorylcholine and diglyceride. It has been associated with gasgangrene and is known to be hemolytic, to destroy platelets andpolymorphonuclear leukocytes (PMNs), and to cause widespread capillarydamage. When injected IV, it causes massive intravascular hemolysis anddamages liver mitochondria. The α toxin may be important in the initiation ofmuscle infections that can progress to gas gangrene. Experimenta ...