By: Nabil A. Ebraheim, M.D. and James Hofmann, M.D.
Clostridium are gram-positive rod shaped bacteria (bacilli). Clostridium are spore forming and toxin producing obligate anaerobes. Clostridium form endospores under adverse environmental conditions. Spores are a survival mechanism for the bacteria. The main species of clostridium causing disease in humans are:
· Clostridium difficile: a condition associated with antibiotics causing diarrhea
· Clostridium perfringens: soft tissue infections (gas gangrene)
· Clostridium botulinum: botulism (food poisoning)
· Clostridium tetani: tetanus
Clostridium difficile (Figure 1) is a part of the normal bacteria living in the intestine (colonic flora). It is also present in the environment in places such as soil, water, and animal feces. Their spores survive well in hospital environments and are resistant to environmental factors and many disinfectants. Hand washing is prophylactic against infection. C. Difficle is transmitted by fecal-oral route. Ingested bacterial spores survive gastric acidity. In the intestine, spores germinate into vegetative form. In severe cases, Clostridium difficile toxins can cause pseudomembranous colitis, which is a severe inflammation of the colon. Healthy people don’t usually get sick from Clostridium difficile. It most commonly affects older patients in hospitals or nursing homes. This condition typically occurs after antibiotic therapy and is referred to as “antibiotic diarrhea”. This usually occurs after the patient takes broad-spectrum antibiotics such as: Clindamycin, Penicillins, Cephalosporins, and Fluoroquinolones. The intestine has hundreds of bacteria. Some have useful functions such as the stimulation of the immune system and the production of vitamins. Antibiotics will kill the bacteria in the intestines that are competing with the C. difficle, but the antibiotics do not kill the C. Difficle, making it easier for the C. Difficle to overgrow and secrete its toxins causing pseudomembranous colitis (Figure 2).
Sometimes, the bacteria change their structure through mutation. The new gene expression is called a “strain.” New genes are frequently more resistant to antibiotics, making it harder to control the infection. Hospitalized people are more prone to infection due to low immunity and the likelihood of antibiotic therapy. Clostridium difficile causes antibiotic associated diarrhea. In mild to moderate cases, there is a watery diarrhea, mild abdominal tenderness and distension. In severe cases it causes pseudomembranous colitis, which is the formation of whitish yellow plaques (Figure 3). This causes severe watery diarrhea and may progress to a life-threatening toxic Mega colon.
In regards to a diagnosis, a stool culture will show the bacteria. Enzyme immunuo assay EIA will show the toxins and a CT scan may be helpful in diagnosis as well.
Treatment for Clostridium difficile will consist of a different type of antibiotic, typically oral metronidazole (flagyl) or oral vancomycin. Probiotics such as bacteria and yeast that help restore the normal balance of the bacterial flora are beneficial. In some cases a fecal transplant may be necessary. With a fecal transplant, fecal matter from a healthy donor is place into the colon by colonoscopy. This is not a commonly used method, however it is gaining popularity.
Clostridium perfringens (Figure 4) is an anerobic gram positive spore forming rod shaped bacterium. Clostridium perfringens is found in soil and is a member of the normal gut flora. This strand of Clostridium produces harmful toxins that cause Gas Gangrene (Clostridium myonecrosis - which is caused by Clostridium perfringens’ alpha toxin) and Clostridium food poisoning (enterotoxin).
Gas gangrene (Figure 5) occurs due to wound infection of limbs (open fractures and extensive soft tissue injuries). Clostridium perfringens grow rapidly in ischemic tissues and anerobic conditions. These toxins cause tissue necrosis and produce gas gangrene. The gases form bubbles in the muscles (crepitus) and cause a characteristic foul smell due to the decomposing tissues. These toxins can enter the blood stream, causing damage to the organs and even death. This is a rapidly spreading infection that may require amputation. Gas gangrene is treated with surgery, antibiotics—intravenous penicillin and clindamycin. Hyperbaric oxygen could be useful.
Clostridium botulinum (Figure 6) produces a potent neurotoxin that causes flaccid muscular paralysis due to failure of neuromuscular transmission. In severe cases, extensive respiratory muscle paralysis leads to ventilatory failure and death, unless supportive care is provided. There are different types of Clostridium botulinum:
· Foodborne botulism—caused by eating foods that contain the botulinum toxin as in home canned food (canned fish or meat).
· Infant Botulism—intestinal botulism which is caused by ingesting spores of the bacteria which germinate and produce toxins in the intestines of young children. This is often associated with the ingestion of honey.
Treatment for Clostridium botulinum consists of antitoxin administration, supportive care such as mechanical ventilation or parenteral nutrition, and elimination which could be by induced vomiting and/or high enemas.
However, there is a therapeutic element to the botulinum toxin. It is the main paralytic agent in Botox, which is used in many clinical applications. These applications include: spasticity— as in Cerebral palsy, strabismus, localized muscle spasms and pain. Botulinum is also used in cosmetics and sweating disorders.
Clostridium tetani is an anaerobic spore forming bacterium that is found in animal manure and contaminated soil. Clostridium tetani spores can live for years in the soil, and enter the body through puncture wounds or other deep cuts. Once in the body the bacteria grows and produces toxins which cause the disease tetanus. Tetanus is characterized by severe muscle spasms and pain. The muscle spasms may be severe enough to break bones. Because of intense spasm of the jaw muscles the disease is sometimes called lockjaw. Treatment for tetanus is with antibiotics and drugs to relieve the muscle spasms. Even with treatment tetanus may be fatal in a significant number of cases. Fortunately there is an effective vaccine to prevent Clostridium Tetani infections. The current recommendations from the CDC call for vaccination of all children as part of their scheduled childhood vaccinations and for all adults to receive booster vaccinations at least every 10 years.
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