page_title: Clostridioides difficile infection
section_title: C. difficile
hierarchical_section_title: Clostridioides difficile infection / Cause / C. difficile
caption_attribution_description: English: This photograph depicts Clostridium difficile colonies after 48hrs growth on a blood agar plate; Magnified 4.8X. C. difficile, an anaerobic gram-positive rod, is the most frequently identified cause of antibiotic-associated diarrhea (AAD). It accounts for approximately 15-25% of all episodes of AAD.
context_page_description: Clostridioides difficile infection, also known as Clostridium difficile infection, is a symptomatic infection due to the spore-forming bacterium Clostridioides difficile. Symptoms include watery diarrhea, fever, nausea, and abdominal pain. It makes up about 20% of cases of antibiotic-associated diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.
  Clostridioides difficile infection is spread by bacterial spores found within feces. Surfaces may become contaminated with the spores with further spread occurring via the hands of healthcare workers. Risk factors for infection include antibiotic or proton pump inhibitor use, hospitalization, other health problems, and older age. Diagnosis is by stool culture or testing for the bacteria's DNA or toxins. If a person tests positive but has no symptoms, the condition is known as C. difficile colonization rather than an infection.
  Prevention efforts include terminal room cleaning in hospitals, limiting antibiotic use, and handwashing campaigns in hospitals. Alcohol based hand sanitizer does not appear effective.
context_section_description: Clostridia are anaerobic motile bacteria, ubiquitous in nature, and especially prevalent in soil. Under the microscope, they appear as long, irregular (often drumstick- or spindle-shaped) cells with a bulge at their terminal ends. Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. When stressed, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.
  C. difficile may colonize the human colon without symptom; approximately 2–5% of the adult population are carriers, although it varies considerably with demographics. The risk of colonization has been linked to a history of unrelated diarrheal illnesses (e.g. laxative abuse and food poisoning due to Salmonellosis or Vibrio cholerae infection).
  Pathogenic C. difficile strains produce multiple toxins. The most well-characterized are enterotoxin (Clostridium difficile toxin A) and cytotoxin (Clostridium difficile toxin B), both of which may produce diarrhea and inflammation in infected patients, although their relative contributions have been debated. Toxins A and B are glucosyltransferases that target and inactivate the Rho family of GTPases. Toxin B (cytotoxin) induces actin depolymerization by a mechanism correlated with a decrease in the ADP-ribosylation of the low molecular mass GTP-binding Rho proteins. Another toxin, binary toxin, also has been described, but its role in disease is not fully understood.
  Antibiotic treatment of CDIs may be difficult, due both to antibiotic resistance and physiological factors of the bacteria (spore formation, protective effects of the pseudomembrane). The emergence of a new and highly toxic strain of C. difficile that is resistant to fluoroquinolone antibiotics such as ciprofloxacin and levofloxacin, said to be causing geographically dispersed outbreaks in North America, was reported in 2005. The U.S. Centers for Disease Control and Prevention  in Atlanta warned of the emergence of an epidemic strain with increased virulence, antibiotic resistance, or both.
  C. difficile is transmitted from person to person by the fecal-oral route. The organism forms heat-resistant spores that are not killed by alcohol-based hand cleansers or routine surface cleaning. Thus, these spores survive in clinical environments for long periods. Because of this, the bacteria may be cultured from almost any surface. Once spores are ingested, their acid-resistance allows them to pass through the stomach unscathed. Upon exposure to bile acids, they germinate and multiply into vegetative cells in the colon. People without a history of gastrointestinal disturbances due to antibiotic use or diarrheal illness less likely to become colonized by C. difficile.
  In 2005, molecular analysis led to the identification of the C. difficile strain type characterized as group BI by restriction endonuclease analysis, as North American pulse-field-type NAP1 by pulsed-field gel electrophoresis  and as ribotype 027; the differing terminology reflects the predominant techniques used for epidemiological typing. This strain is referred to as C. difficile BI/NAP1/027.
caption: C. difficile colonies on a blood agar plate
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