What is Clostridium?

Definition

Clostridium is a gram-positive, rod-shaped, spore forming,
chiefly anaerobic bacteria that can produce lethal toxins. There are
approximately 134 species, 25 to 30 of which are infectious to animals and humans.

Natural Habitat and Features

Clostridium is found in soil, water, and sewage. It is also found as normal microbial flora in the gastrointestinal tract and in the vagina. It is saprophytic in nature, playing an important role in the degradation of organic materials. Most Clostridium species are obligate anaerobes, but a few can grow in the air at atmospheric pressure. Because Clostridium cannot use molecular oxygen as a final electron acceptor, it generates energy solely by fermentation. Endospores produced by Clostridium are extremely hearty and can survive adverse environmental conditions such as extreme heat and oxygen deprivation.

Clostridium can be seen microscopically, appearing pink to red
when stained for gram-positive bacteria. They comprise straight or slightly curved
rods that are 0.3 to 1.6 micrometers (m) wide and 1 to 14 m long, and they are
found singly, in pairs, in short or long chains, or in helical coils. Most are
motile with flagella. Clostridium grown on agar will appear as a
series of flat, round colonies and demonstrate hemolysis.
Clinically, Clostridium is detected through enzyme immunoassay,
cytotoxin assay, polymerase chain reaction (PCR), and tissue sampling.

Clostridium is characterized by its potent and often lethal endotoxins. C. botulinin and C. tetani produce the most lethal toxins known to affect humans. Most Clostridium species are benign to humans, and some play an essential biological role in degrading biological molecules.

Pathogenicity and Clinical Significance

Clostridium infections range from mild food
poisoning to life-threatening septic shock.
There are four methods of infection with, for example, C.
botulinum, which leads to botulism: food-borne, wound colonization, intestinal
colonization, and inhalation. All these methods of infection are rare; in general,
only food-borne and intestinal colonization in infants is fatal if not treated
properly. In cases of food poisoning, spores will grow in anaerobic, nonacidic pH,
and in low salt and low sugar environments; contaminated food is usually found in
canned goods in the home or in fermented, uncooked meat. Wound botulism is almost
exclusively found in users of black tar heroin, which is injected under the skin
rather than intravenously. These wounds are usually self-limiting with supportive
treatment.

Infants with botulism have intestinal colonization of C. botulinum because of competition with healthy gut flora; botulism manifests as infant paralysis, also known as floppy infant. An iatrogenic risk also exists for botulism symptoms for persons receiving botulinum toxin injections for either cosmetic or therapeutic purposes.

C. difficile is the most identifiable bacterial cause of
diarrhea. Widespread use of broad-spectrum antibiotics such as the
fluoroquinolones and third generation cephalosporins is the primary cause, but any antibiotic use,
especially long-term use, can cause a C. difficile infection. The
symptoms of C. difficile include watery diarrhea,
pseudomembranous colonitis, fever, fecal leucocytes, cramping, and, if severe,
toxic megacolon. C. difficile infection is also a high-risk
nosocomial (hospital acquired) infectious disease.

C. perfringens can cause a range of illnesses, from food poisoning to toxic shock to gas gangrene. The source of C. perfringens food poisoning is meats; gravies; and dried, processed, and inadequately heated foods. Symptoms include vomiting and diarrhea and are usually self-limiting. Clostridial myonecrosis, or gas gangrene, is characterized by gas bubbles under the skin, a distinctive foul odor, and a blackish discoloration of the skin. It usually occurs with injuries, such as severe crushing traumas and penetrating wounds, or at the site of recent surgery. The onset is sudden and dramatic. Persons with existing blood vessel diseases such as diabetes or atherosclerosis are most at risk. Shock, delirium, and renal failure are followed by death. C. perfringens, in addition to C. sordellii, has also been linked to toxic shock after surgical abortions or spontaneous miscarriages.

C. tetani causes tetanus, or lockjaw, and intermittent spasms of the masseter
muscles, which can move into the lower muscles and eventually cause death. The
C. tetani bacteria can enter the body through a burn, surgical
wound, or puncture wound. It can also enter through the uterus (maternal tetanus)
and the umbilical cord. C. tetani produces an exotoxin called tetanospasmin, which enters the central nervous
system and releases an inhibitory neurotransmitter, causing generalized tonic
spasticity. Symptoms include jaw stiffening, difficulty swallowing, irritability,
tonic spasms, and the characteristic facial expression of a fixed smile with
elevated eyebrows (risus sardonis). The patient may be in extreme pain but will be
unable to speak, although mental capacity remains intact. Death is caused by
asphyxia or cyanosis.

Botulinum toxin has been found to have important therapeutic effects for
persons with a range of illnesses including minor nerve spasticity disorders,
Tourette’s syndrome, cerebral palsy, migraines, and Parkinsonian tremors.
Botulinum toxin type A can be injected intramuscularly and prevent the release of
acetylcholine, resulting in a temporary paralysis of
muscles. Commercially known as Botox, it is also used for cosmetic
purposes to freeze facial muscles to give the appearance of youth.

Drug Susceptibility

Botulism antitoxin is the only treatment for botulism poisoning. Some of the
Clostridium species can be killed with antimicrobials. Both
metronizole and vancomycin are given for C. difficile infections.
Penicillin G is effective against mild cases of C. perfringens;
however, metronizole is also effective. Both antibiotics
can be given as supportive drugs in cases of tetanus, although the primary
treatment is a tetanus antitoxin. A vaccine and regular booster shots can protect
against tetanus.

Bibliography

Abrutyn, E. “Botulism.” In Harrison’s Principles of Internal Medicine, edited by Joan Butterton. 17th ed. New York: McGraw-Hill, 2008. A chapter on botulism in a respected text on internal medicine.

Finsterer, J. “Neuromuscular and Central NervousSystem Manifestation of Clostridium perfringensInfections.” Infection 356 (2007): 396-405. An overview of infectious diseases caused by C. perfringens.

Pickering, Larry K., et al., eds. “Clostridial Infections.” In Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, Ill.: American Academy of Pediatrics, 2009. An overview of clostridial infections and treatments.

Sobel, J. “Botulism.” Food Safety 41 (2005) 1167-1173. Overview of how botulism can be contracted. Includes symptoms, treatments, and prevention.

Ward, A. B. “Clinical Value of Botulinum Toxin in Neurological Indications.” European Journal of Neurology 13 (2006) 20-26. Overview of clinical uses for the botulinum toxin for persons with neurological disorders.