Clostridium difficile may refer to:

Clostridium difficile (etymology and pronunciation), also known as C. difficile, C. diff (/siː/ /dɪf/), or sometimes CDF/cdf, is a species of Gram-positive spore-forming bacteria.

Clostridia (members of the genus Clostridium) 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 become established in the human colon; it is present in 2–5% of the adult population. Sometimes antibiotic therapy for various infections has the adverse effect of disrupting the normal balance of the gut flora, in which case C. difficile may opportunistically dominate, causing Clostridium difficile colitis.

Clostridium difficile colitis or pseudomembranous colitis is colitis (inflammation of the large intestine) resulting from infection with Clostridium difficile, a spore-forming bacterium. It causes an infectious diarrhea called C. difficile associated diarrhea (CDAD). Latent symptoms of Clostridium difficile infection (CDI) often mimic some flu-like symptoms and may mimic disease flare-ups in people with inflammatory bowel disease–associated colitis.C. difficile releases toxins that may cause bloating and diarrhea, with abdominal pain, which may become severe.

The colitis is thought to occur when this bacterium replaces normal gut flora that has been compromised, usually following antibiotic treatment for an unrelated infection. The disturbance of normal healthy bacteria may provide C. difficile an opportunity to overrun the intestinal microbiome. It is a type of antibiotic-associated diarrhea.

Often, mild cases of CDI may be treated by discontinuing the offending antibiotics. More serious cases require targeted antibiotic treatment. Relapses of CDI have been reported in up to 20% of cases.C. difficile infection is a growing problem in health care facilities, killing approximately 29,000 people in the United States in 2011.