Clostridioides difficile infection

Last updated: July 6, 2023

Summarytoggle arrow icon

Clostridioides difficile (C. difficile; formerly known as Clostridium difficile) is a gram-positive bacillus that can cause antibiotic-associated diarrhea. Rates of C. difficile infection (CDI) 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, and colonization with C. difficile most commonly occurs following antibiotic treatment for other diseases. The resulting damage to the intestinal flora promotes C. difficile infection, which typically manifests with diarrhea accompanied by fever and abdominal pain. Severe CDI or fulminant CDI may manifest with paralytic ileus or toxic megacolon. In most cases, however, colonization results in asymptomatic carriage. Diagnosis of symptomatic patients is based on stool tests for CDI, which detect toxins or toxigenic strains of C. difficile or the identification of pseudomembranous colitis on imaging or endoscopy. Vancomycin and fidaxomicin are the preferred antibiotic agents for treating CDI. Once the diagnosis is confirmed, measures to prevent transmission (e.g., patient cohorting or isolation, strict adherence to hygiene measures) should be followed, especially in hospitals and other health care settings.

Definitiontoggle arrow icon

  • Hospital-acquired CDI: confirmed CDI in an individual with documented inpatient care in a health care facility in the preceding 12 weeks
  • Community-acquired CDI: confirmed CDI in an individual with no documented inpatient care in a health care facility in the preceding 12 weeks
  • Recurrent CDI: recurrence of symptoms and a positive stool test for CDI (NAAT or EIA) after a confirmed episode in the previous 8 weeks

References: [1][2][3]

Epidemiologytoggle arrow icon

  • Incidence: ∼ 220,000 cases in hospitalized patients and ∼ 13,000 deaths per year in the US [4]
  • Hospital-acquired CDI: more common in individuals aged > 65 years [5]
  • Community-acquired CDI: affected individuals are typically younger (∼ 50 years) [6]

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Causative pathogen: Clostridioides difficile

The C. difficile strain must be toxigenic to cause the disease. Intestinal colonization by nontoxigenic strains will result in asymptomatic carriage.

Risk factors for CDI [1][6]

Pathophysiologytoggle arrow icon

C. difficile possesses a range of virulence factors, the most important of which are toxins A and B. [10][11]

Toxin A (enterotoxin)

Toxin B (cytotoxin)

  • Structure
    • Binding site at C-terminal domain
    • Translocation domain
    • Cysteine protease-containing domain
    • Catalytic domain
  • Mechanism of action: same as in toxin A, but can also cause pore formation within the endosomal membrane via insertion of the translocation domain → release of endosomal content into the cytosol cytopathic effect

Clinical featurestoggle arrow icon

Symptoms typically develop during antibiotic treatment or 2–10 days following its initiation; however, 25–40% of cases manifest as late as 10 weeks following treatment.

Clostridioides difficile Causes Difficult Diarrhea.


Diagnosticstoggle arrow icon

Approach [1][2]

Patient history and clinical presentation can provide strong indicators for infection, which should be confirmed by stool studies, colonoscopy, or histopathology findings. [1]

Routine laboratory studies [1][2][13]

Findings are nonspecific and may include the following. [13]

Stool tests for toxins and toxigenic strains of C. difficile [1][2]


  • Adults: unexplained, new-onset loose stools ≥ 3 times in 24 hours
  • Children : Consider stool tests in children with prolonged or worsening diarrhea, especially those with risk factors for CDI.


Suggested testing strategy [1][2]

Consider a multi-test algorithmic approach guided by the pretest probability (PTP) of CDI.

Repeat testing within 7 days of diarrhea is not recommended, and asymptomatic individuals should not be tested. [1][2]

Additional diagnostics

Imaging [1][13]

Endoscopy [1][13]

  • Indication (not routinely required)
    • Consider if the diagnosis remains unclear after initial tests.
    • Consider if the PTP of CDI remains high in patients with insufficient response to empirical antibiotic therapy for CDI.
  • Modalities: colonoscopy or sigmoidoscopy
  • Findings
    • Mucosa may appear normal or erythematous and friable.
    • Possible signs of pseudomembranous colitis
      • Elevated yellow-white plaques that form pseudomembranes over the colonic mucosa
      • May be solitary; widespread; , confluent lesions are seen in severe disease

Endoscopy may not detect cases of nonsevere CDI, in which pseudomembranes may be absent. [13]

Severity classificationtoggle arrow icon

The severity of CDI is based on laboratory studies and clinical features and is used to guide disposition, management, and prognosis.

If clinical suspicion is high, initiating antibiotic treatment before laboratory confirmation may be considered, especially in patients with fulminant CDI. [1][2]

Patients with severe or fulminant disease have a higher rate of treatment failure, colectomy, and mortality. [2]

References: [1][2]

Treatmenttoggle arrow icon

General principles [1][2]

Supportive measures [1][2]

Antibiotic therapy for CDI [1][2][3]

Antibiotic therapy for C. difficile infection in adults [1][2][3]
Category Treatment options
Initial episode Nonsevere CDI or severe CDI
Fulminant CDI
Recurrent CDI First recurrence
Subsequent recurrences

C. difficile infection is one of the rare indications for PO vancomycin in adults and children.

Intravenous administration of vancomycin is ineffective for C. difficile infection because vancomycin is insufficiently excreted into the colon.

Consider bezlotoxumab, a monoclonal antibody against the C. difficile toxin B, in adults at risk of recurrent CDI. [2][3]

Fecal microbiota transplantation (FMT) [1][16]

  • Healthy donor stool that is administered via capsules, colonoscopy, or enema
  • Can be considered in the following situations

Surgical management [1][2]

Complicationstoggle arrow icon

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

Preventiontoggle arrow icon

Primary prevention of CDI

Secondary prevention of CDI [1]

Contact precautions should be followed for all patients with suspected or diagnosed CDI for at least 48 hours after symptoms subside or until CDI is ruled out. [1]

  • Isolation: A single room with designated bathroom facilities is preferable; consider patient cohorting if this is not feasible.
  • Personal protective equipment: Wear gloves and a protective gown (change after each patient); a mask is not necessary.
  • Hand hygiene
    • Wash hands thoroughly with soap and water; before and after every patient contact (C. difficile spores are resistant to alcoholic disinfectants).
    • Encourage frequent handwashing in patients with CDI.
  • Surface disinfection
  • Medical equipment
    • Use disposable or dedicated equipment if possible.
    • Otherwise, ensure adequate cleaning and disinfection that is effective against spores.
    • Autoclaving is also sporicidal and can be used to sterilize equipment.

Special patient groupstoggle arrow icon

Clostridioides difficile in infants [17][18]

Most infants with C. difficile colonization; are asymptomatic and do not develop pseudomembranous colitis.

Acute management checklisttoggle arrow icon

Referencestoggle arrow icon

  1. McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018; 66 (7): p.e1-e48.doi: 10.1093/cid/cix1085 . | Open in Read by QxMD
  2. Khanna S, Gupta A. Community-acquired Clostridium difficile infection: an increasing public health threat. Infection and Drug Resistance. 2014: p.63.doi: 10.2147/idr.s46780 . | Open in Read by QxMD
  3. Hickson M. Probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection. Therap Adv Gastroenterol. 2011; 4 (3): p.185-197.doi: 10.1177/1756283X11399115 . | Open in Read by QxMD
  4. Deshpande A, Pasupuleti V, Thota P, et al. Community-associated Clostridium difficile infection and antibiotics: a meta-analysis. J Antimicrob Chemother. 2013; 68 (9): p.1951-1961.doi: 10.1093/jac/dkt129 . | Open in Read by QxMD
  5. Issa M, Ananthakrishnan AN, Binion DG. Clostridium difficile and inflammatory bowel disease. Inflamm Bowel Dis. 2008; 14 (10): p.1432-1442.doi: 10.1002/ibd.20500 . | Open in Read by QxMD
  6. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013; 108 (4): p.478-498.doi: 10.1038/ajg.2013.4 . | Open in Read by QxMD
  7. Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol. 2021; 116 (6): p.1124-1147.doi: 10.14309/ajg.0000000000001278 . | Open in Read by QxMD
  8. Guh AY, Kutty PK. Clostridioides difficile Infection. Ann Intern Med. 2018; 169 (7): p.ITC49-ITC64.doi: 10.7326/aitc201810020 . | Open in Read by QxMD
  9. Kirkpatrick IDC, Greenberg HM. Evaluating the CT Diagnosis ofClostridium difficileColitis. American Journal of Roentgenology. 2001; 176 (3): p.635-639.doi: 10.2214/ajr.176.3.1760635 . | Open in Read by QxMD
  10. Guerri S, Danti G, Frezzetti G, Lucarelli E, Pradella S, Miele V. Clostridium difficile colitis: CT findings and differential diagnosis. Radiol Med (Torino). 2019; 124 (12): p.1185-1198.doi: 10.1007/s11547-019-01066-0 . | Open in Read by QxMD
  11. Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clinical Infectious Diseases. 2021.doi: 10.1093/cid/ciab549 . | Open in Read by QxMD
  12. Kelly CR, Yen EF, Grinspan AM, et al. Fecal Microbiota Transplantation Is Highly Effective in Real-World Practice: Initial Results From the FMT National Registry. Gastroenterology. 2021; 160 (1): p.183-192.e3.doi: 10.1053/j.gastro.2020.09.038 . | Open in Read by QxMD
  13. Antibiotic Resistance Threats in the United States, 2019 - Clostridioides difficile. Updated: November 14, 2019. Accessed: December 30, 2019.
  14. Jump RL. Clostridium difficile infection in older adults. Aging health. 2013; 9 (4): p.403-414.doi: 10.2217/ahe.13.37 . | Open in Read by QxMD
  15. Brook I. Pseudomembranous colitis in children. J Gastroenterol Hepatol. 2005; 20 (2): p.182-186.doi: 10.1111/j.1440-1746.2004.03466.x . | Open in Read by QxMD
  16. Kuiper G-A, van Prehn J, Ang W, Kneepkens F, van der Schoor S, de Meij T. Clostridium difficile infections in young infants: Case presentations and literature review. IDCases. 2017; 10: p.7-11.doi: 10.1016/j.idcr.2017.07.005 . | Open in Read by QxMD
  17. Di Bella S, Ascenzi P, Siarakas S, Petrosillo N, di Masi A. Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects. Toxins. 2016; 8 (5): p.134.doi: 10.3390/toxins8050134 . | Open in Read by QxMD
  18. Abt MC, McKenney PT, Pamer EG. Clostridium difficile colitis: pathogenesis and host defence. Nature Reviews Microbiology. 2016; 14 (10): p.609-620.doi: 10.1038/nrmicro.2016.108 . | Open in Read by QxMD

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