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Clostridium


ORGANISM:

  • Genus: Clostridium
  • Species: perfringens, tetani, botulinum, difficile


GENERAL CONCEPTS:
  • The clostridia are opportunistic pathogens. Nonetheless, they are responsible for some of the deadliest diseases including gas gangrene, tetanus and botulism. Less life-threatening diseases include pseudomembranous colitis (PC) and food poisoning.
  • Clostridia cause disease primarily through the production of numerous exotoxins.


DISTINCTIVE PROPERTIES:
  • Clostridium species are Gram-positive, rod-shaped, spore-formers. These generally obligate anaerobes are ubiquitous saprophytes or part of our normal flora.
  • Clostridia employ butyric fermentation pathways to generate energy and, as a result, often produce a foul odor.
  • C. perfringens produces large rectangular spores and is non-motile. This species is most often associated with wound infections but these are generally polymicrobic.
  • C. tetani produces terminal spores, giving it the appearance of a squash racket. This species is motile and produces a single antigenic type of exotoxin.
  • C. botulinum produces oval subterminal spores and is motile. Different strains within this species produce one of 8 exotoxin types (A,B,C1,C2,D,E,F,G). Types C and D are encoded by bacteriophage that infect the bacteria.
  • C. difficile produces large oval subterminal spores and two different toxins; toxin A (an enterotoxin causing fluid accumulation in the intestine) and toxin B (a cytopathic agent). Ordinarily, this species can't compete with normal intestinal flora but, when antibiotics eliminate these normal flora, C. difficile can flourish, producing disease.


PATHOGENESIS:
  • C. perfringens: Gas gangrene results from an anaerobic tissue environment caused by poor blood supply due to trauma, surgery, etc. This acute disease is often fatal. One to six days following trauma, a generalized fever and pain is observed in the affected area. This leads to rapid muscle necrosis because of the release of bacterial exotoxins (lecithinases, hemolysins, collagenases, proteases, lipases). A spreading infection ensues. Gas gangrene generally involves muscle extremities where anaerobiosis can occur.
  • C. tetani: Tetanus results from trauma or a puncture wound leading to tissue contamination. Tetanus is a non-invasive disease occurring because of the release of exotoxins. C. tetani produces a spasmogenic toxin that fixes to gangliosides thereby blocking the release of the neurotransmitter glycine. Glycine normally prevents contraction of antagonistic muscles; therefore, muscle spasms and convulsions (lockjaw) may occur. Cardiac failure can lead to death in approximately 55-65% of affected persons.
  • C. botulinum: Botulism results from the ingestion of bacterially produced neurotoxins. Types A, B, E and F are the most toxic for humans. These protein exotoxins are often released in an inactive form; proteolytic cleavage activates them. Type A is the most potent exotoxin known (10 ng can kill a normal adult). These toxins block the release of the neurotransmitter acetylcholine resulting in double vision, slurred speech, decreased saliva, difficult swallowing and general weakness. Paralysis with accompanying respiratory failure can be fatal in about 20% of those affected. Botulism food poisoning can be observed about 18-36 hours following ingestion of preformed toxin, which is heat labile. Infant botulism may occur via germination of spores in the intestinal tract with subsequent toxin production, possibly accounting for some cases of Sudden Infant Death Syndrome (SIDS).
  • C. difficile: Pseudomembranous colitis (PC) results predominantly as a consequence of the elimination of normal intestinal flora through antibiotic therapy. Symptoms include abdominal pain with a watery diarrhea and leukocytosis. "Pseudomembranes" consisting of fibrin, mucus and leukocytes can be observed by colonoscopy. Untreated pseudomembranous colitis can be fatal in about 27-44%.


HOST DEFENSES:
  • Gas gangrene: Host defenses are ineffective.
  • Tetanus: No innate immunity. Disease episodes are ineffective (too little toxin released).
  • Botulism: Toxin is poorly absorbed in intestine. Disease episodes are ineffective (too little toxin released).
  • Pseudomembranous colitis: Normal flora play an important role. Other host defenses are unknown.


EPIDEMIOLOGY:
  • The clostridia are ubiquitous in the soil and some are part of the normal human flora.
  • Heroin addicts are particularly susceptible to tetanus as a consequence of their life style.
  • Poorly canned foods create an anaerobic environment. Unkilled spores germinate and produce toxin.
  • PC patients secrete large numbers of spores in feces. This provides a reservoir.


DIAGNOSIS:

  • Clinical:
    • Gas gangrene: Symptomology and the presence of bacilli in the wound.
    • Tetanus: Cramping and twitching around a wound, auditory hyperacuity and pain in neck and jaw. Tetanus is similar to strychnine ingestion so must exclude the latter.
    • Botulism: Difficult to diagnose. Must demonstrate a normal cerebrospinal fluid (CSF) to exclude other possibilities. The toxin is rarely found.
    • Pseudomembranous colitis: Demonstration of pseudomembranes by colonoscopy is diagnostic.
    • Laboratory: Members of the genus Clostridium can be differentiated from other bacteria by laboratory techniques including enzymatic digestion on egg-yolk agar plates and by using mice treated with or without antitoxin. For PC, the organisms can be isolated from feces.


CONTROL:

  • Sanitary: Early cleansing of any wound, the surgical removal of affected tissues, suture sterilization and proper washing and canning of foods can prevent disease.
  • Immunological: There are no vaccines available for gas gangrene and antitoxins are ineffective. The use of hyperbaric oxygen and chelating agents can help, however. A vaccine for tetanus made from the inactivated tetanus toxin ("toxoid") is available and required. Booster immunizations are recommended every 5 yrs or less to maintain high levels of circulating antitoxin. Botulism may be treated with antitoxin. PC patients should be certain to replace lost fluids and electrolytes to avoid dehydration.
  • Chemotherapeutic: Penicillin or chloramphenicol may be employed but their use is debatable. For PC, vancomycin or metronidazole should be employed.

    Note: Clostridium septicum has been strongly associated with an underlying malignancy. That is, 83% of patients having a C. septicum infection have also been diagnosed with cancer.

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