• Clinical science

Clostridioides difficile infection (Clostridium difficile infection)


Clostridioides difficile (C. difficile; formerly known as Clostridium difficile) is a gram-positive bacillus that may cause antibiotic-associated diarrhea. Rates of C. difficile infection are particularly high among hospitalized patients and residents in long-term care facilities because C. difficile spores are easily transmitted (fecal-oral route) and difficult to eradicate. The bacterium is resistant to multiple antibiotics, so colonization with C. difficile most commonly occurs following antibiotic treatment of other diseases. The resulting damage to the intestinal flora promotes infection, which may be accompanied by high fever, abdominal pain, and foul-smelling diarrhea. The most severe form of C. difficile infection is pseudomembranous colitis, which can lead to ileus, sepsis, and toxic megacolon. In most cases, however, colonization results in asymptomatic carriage. Diagnosis is usually made via detection of the C. difficile toxin, C. difficile glutamate dehydrogenase antigen, and/or corresponding genes in stool samples. C. difficile infection is treated with oral vancomycin or oral fidaxomicin. Following diagnosis, strict adherence to hygiene measures and patient isolation is essential, especially in hospitals and other healthcare settings.


  • ∼ 220,000 cases in hospitalized patients and ∼ 13,000 deaths per year in the US [1]
  • Individuals > 65 years old are at increased risk for hospital-acquired infections. [2]


Epidemiological data refers to the US, unless otherwise specified.


The C. difficile strain must be toxigenic to cause the disease. Intestinal colonization by the non-toxigenic bacteria will result in asymptomatic carriage!References:[5][6][3]


C. difficile possesses a range of virulence factors, the most important of which are toxins A and B. [7][8]

Clinical features

Symptoms of C. difficile-associated diarrhea (CDAD) usually develop during antibiotic treatment or 2–10 days following its initiation; however, 25–40% of cases manifest as late as 10 weeks following treatment.

  • Watery diarrhea, characteristically foul-smelling
    • Mild disease manifests with ≥ 3 stools per day; patients with fulminant colitis may have up to 20 stools per day.
    • May contain traces of mucus or occult blood
    • Hematochezia and melena are both rare.
  • Cramping abdominal pain, nausea, anorexia
  • Fever and dehydration (especially in severe cases)
  • Fulminant colitis: abdominal distention and severe hypovolemia
  • Recurrent disease: symptom reoccurrence 2–8 weeks following the end of treatment (10–40% of cases)



Patient history and clinical presentation are strong indicators for diagnosis of infection, which is then confirmed by identification of the pathogen's genes or corresponding toxins in the stool. Further diagnostics, such as blood tests or imaging, may be used to assess the severity of disease and/or the presence of complications.

History [3]

  • Treatment with antibiotics in the last three months
  • Recent hospitalization

Stool tests [11]

Blood tests



  • Colonoscopy or sigmoidoscopy [9]
    • Not indicated if C. difficile is suspected based on clinical findings, laboratory tests, and/or response to empiric treatment
    • Perform cautiously (increased risk of perforation).
    • Findings

Disease severity [14]



General measures [3][10]

Medical therapy [11]

C. difficile infection is one of the rare indications for oral administration of vancomycin!

Fecal microbiota transplantation (FMT) [11]

  • Indication: recurrent C. difficile infections in a patient who has not responded to at least two appropriate antibiotic regimens




We list the most important complications. The selection is not exhaustive.


  • Detection: C. difficile toxin stool test for at-risk patients with recent onset of diarrhea
  • Isolation
    • Single-bed room with designated bathroom facilities (up to 2 days after symptoms subside)
    • Cohort isolation is possible if control measures are implemented.
  • Control measures
    • Personal protective equipment: Wear gloves and a protective gown (change after each patient); a mask is not necessary.
    • Hand hygiene: Wash thoroughly with soap and water.
    • Consistent disinfection of potentially contaminated surfaces with sporicidal oxidants such as peracetic acid or sodium hypochlorite
      • Autoclaving is also sporicidal and can be used to sterilize equipment.