Clostridium difficile
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Clostridium difficile (Template:Audio) is a species of bacteria of the genus Clostridium which are gram-positive, anaerobic spore-forming rods. They cause pseudomembranous colitis, a severe infection of the colon, often after normal gut flora is eradicated by the use of antibiotics. Treatment is by stopping putative antibiotics and commencing specific anticlostridial antibiotics, e.g. metronidazole.
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Bacteriology
Characteristics
Clostridia are motile bacteria that are ubiquitous in nature and are especially prevalent in soil. Under the microscope after Gram staining, they appear as long drumsticks with a bulge located at their terminal ends. Clostridium difficile cells are gram positive, while its spores are gram negative. Clostridium shows optimimum growth when plated on blood agar at human body temperatures. When the environment becomes stressed, however, the bacteria produce spores that tolerate the extreme conditions that the active bacteria cannot. First described by Hall and O'Toole in 1935, "the difficult clostridium" was resistant to early attempts at isolation and grew very slowly in culture.
C. difficile is an inhabitant of the human intestine, but normally behaves as a commensal without causing disease of any significance. Antibiotics, especially those with a broad spectrum of activity, cause disruption on normal intestinal flora. C. difficile is resistant to most antibiotics. It flourishes under these conditions. It is transmitted from person to person by the fecal-oral route. Because the organism forms heat-resistant spores, it can remain in the hospital or nursing home environment for long periods of time. It can be cultured from almost any surface in the hospital. Once spores are ingested, they pass through the stomach unscathed because of their acid-resistance. They change to their active form in the colon and multiply.
Toxins
Pathogenic strains elaborate one of two toxins, toxin A or B. These toxins are responsible for the diarrhea and inflammation seen in patients so infected.
Role in disease
With the introduction of broad-spectrum antibiotics in the latter half of the twentieth century, antibiotic-associated diarrhea became more common. Pseudomembranous colitis was first described as a complication of C. difficile infection in 1978 (Larson et al), when a toxin was isolated from patients suffering from pseudomembranous colitis and Koch's postulates were met.
Infection can range in severity from asymptomatic to severe and life threatening. People are most often infected in hospitals, nursing homes or institutions, although C. difficile infection in the community, outpatient setting is increasing.
Pharmacology
Two antibiotics are effective against C. difficile. Metronidazole is first choice because of superior tolerability, lower price and comparable efficacy. Oral vancomycin can be used as well.
Notable outbreaks
On June 4, 2004, two outbreaks of a highly virulent strain of this bacterium were reported in Montreal, Quebec and Calgary, Alberta, in Canada. Sources put the death count as low as 36 and as high as 89, with approximately 1,400 cases in 2003 and within the first few months of 2004. C. difficile infections continued to be a problem in the Quebec health care system in late 2004. As of March 2005, it has spread into the Toronto, Ontario area, hospitalizing 10 people. One has died while the others have been released.
A similar outbreak has happened in Stoke Mandeville Hospital in the United Kingdom between 2003 and 2005.
References
- Hall I, O'Toole E. Intestinal flora in newborn infants with a description of a new pathogenic anaerobe, Bacillus difficilis. Am J Dis Child 1935;49:390.
- Larson HE, Price AB, Honour P, Borriello SP. Clostridium difficile and the aetiology of pseudomembranous colitis. Lancet 1978;1(8073):1063-6. PMID 77366.de:Clostridium difficile