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Clostridioides difficile infection

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Updated 2024 AGA guidelines for fecal microbiota transplantation in Clostridioides difficile infection.



CDI is an antibiotic-induced infectious diarrheal disease that is associated with significant mortality and morbidity.
The shift in intestinal microbiota induced by repeated antibiotic use facilitates C. difficile colonization in the colon, with production of exotoxins (TcdA and TcdB) that cause colonocyte death.
The incidence of CDI is estimated at 1.1-631.8 cases per 100,000 person-years. In patients admitted to the ICU, the incidence of CDI is estimated at 11.1 cases per 1,000 admissions-year (95% CI, 7.2-17.1), while in patients admitted to the internal medicine ward, it is estimated at 10.8 cases per 1,000 admissions-year (95% CI, 3.2-37.1).
Risk factors
The primary risk factor for CDI is the use of antibiotics, especially clindamycin, fluoroquinolones, certain cephalosporins, and carbapenems, as well as penicillins, macrolides, and sulfonamides. Other risk factors include advanced age, hospitalization, the presence of comorbidities, IBD, immunosuppression, and the use of PPIs.
Disease course
The resultant loss of intestinal barrier function leads to clinical manifestations of diarrhea, and can progress to pseudomembranous colitis, toxic megacolon, bowel perforation, sepsis, shock, multiple organ failure, and death.
Prognosis and risk of recurrence
CDI has a mortality of 5% and is associated with a recurrence rate of 20-60%.


Key sources

The following summarized guidelines for the evaluation and management of Clostridioides difficile infection are prepared by our editorial team based on guidelines from the American Gastroenterological Association (AGA 2024,2020,2017), the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN 2023), the American College of Gastroenterology (ACG 2021,2019,2018,2013), the American Society of Colon and Rectal Surgeons (ASCRS 2021), the European Society ...
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Screening and diagnosis

Epidemiology: as per IDSA/SHEA 2018 guidelines, use standardized case definitions for surveillance of healthcare facility-onset CDI, community-onset, healthcare facility-associated CDI, and community-associated CDI, to increase comparability between clinical settings.
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  • Indications for screening (asymptomatic individuals)

  • Indications for screening (patients on tube feeding)

  • Indications for testing (adult patients)

  • Indications for testing (pediatric patients)

Classification and risk stratification

Risk assessment
As per ESCMID 2021 guidelines:
Recognize that older age (> 65 years old) and multiple comorbidities are risk factors for CDI.
Recognize the following risk factors for recurrent CDI:
prior CDI episode
prior hospitalization in the last 3 months
concomitant non-CDI antibiotic use after the diagnosis of CDI
PPIs started during/after CDI diagnosis

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  • Severity assessment

Diagnostic investigations

History and physical examination
As per ASCRS 2021 guidelines:
Elicit a disease-specific history emphasizing risk factors, symptoms, underlying comorbidities, and signs of severe or fulminant disease in patients with suspected CDI.
Assess for peritonitis and multisystem organ failure in patients with CDI.

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  • Stool testing (sampling)

  • Stool testing (testing protocol)

  • Stool testing (repeat testing)

  • Biological markers

  • Diagnostic imaging

Diagnostic procedures

Lower gastrointestinal endoscopy: as per ASCRS 2021 guidelines, do not obtain a routine endoscopic evaluation to diagnose or determine the extent of CDI.

Medical management

Discontinuation of inciting antibiotics: as per ESCMID 2021 guidelines, discontinue the inciting antibiotic and closely monitor the patient for 48 hours in case of non-severe CDI.

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  • Discontinuation of PPIs

  • Supportive care

  • Antibiotic therapy (empiric therapy)

  • Antibiotic therapy (non-severe disease)

  • Antibiotic therapy (severe disease)

  • Antibiotic therapy (fulminant disease)

  • Antibiotic therapy (ileus)

  • Bezlotoxumab

  • IVIG

  • Antiperistaltic agents

Nonpharmacologic interventions

Probiotics: as per ASCRS 2021 guidelines, do not use probiotics for the treatment of CDI.

Therapeutic procedures

Fecal microbiota transplantation, setting of care: as per BSG/HIS 2018 guidelines, form a multidisciplinary team to deliver fecal microbiota transplantation services.
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  • Fecal microbiota transplantation (pre-transplant care)

  • Fecal microbiota transplantation (initial disease)

  • Fecal microbiota transplantation (severe disease)

  • Fecal microbiota transplantation (recurrent disease)

  • Fecal microbiota transplantation (patients with comorbidities)

  • Fecal microbiota transplantation (selection and evaluation of donors)

  • Fecal microbiota transplantation (transplant material sampling and storage)

  • Fecal microbiota transplantation (transplant administration)

  • Fecal microbiota transplantation (post-transplant care)

Surgical interventions

Indications for surgery: as per ACG 2021 guidelines, consider performing either total colectomy with end ileostomy and stapled rectal stump or diverting loop ileostomy with colonic lavage and intraluminal vancomycin in patients requiring surgical intervention, depending on clinical circumstances, the patient's estimated tolerance to surgery, and the surgeon's best judgment.

Specific circumstances

Pediatric patients, prophylactic probiotics: as per ESPGHAN 2023 guidelines, consider offering high doses (≥ 5 billion CFU/day) of Saccharomyces boulardii or Lacticaseibacillus rhamnosus GG started simultaneously with antibiotic treatment to prevent antibiotic-associated diarrhea in outpatients and hospitalized pediatric patients if the use of probiotics for preventing antibiotic-associated diarrhea is considered because of the existence of risk factors, such as class of antibiotic, duration of antibiotic treatment, age, need for hospitalization, comorbidities, or previous episodes of antibiotic-associated diarrhea.

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  • Pediatric patients (evaluation)

  • Pediatric patients (antibiotic therapy)

  • Pediatric patients (fecal microbiota transplantation)

  • Pregnant patients

  • Immunosuppressed patients (antibiotic therapy)

  • Immunosuppressed patients (fecal microbiota transplantation)

  • Patients with IBD (evaluation)

  • Patients with IBD (antibiotic therapy)

  • Patients with IBD (withholding immunosuppressive therapy)

  • Patients with IBD (fecal microbiota transplantation)

Preventative measures

Antibiotic stewardship: as per ASCRS 2021 guidelines, consider implementing an evidence-based antibiotic stewardship program to decrease rates of CDI.

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  • Discontinuation of PPIs

  • Infection control measures (contact precautions)

  • Infection control measures (hand hygiene)

  • Infection control measures (equipment and room cleaning)

  • Prophylactic probiotics

  • Prophylactic antibiotics

  • Secondary prevention

Follow-up and surveillance

Management of recurrence, antibiotics
As per ACG 2021 guidelines:
Consider administering tapering/pulsed-dose vancomycin in patients experiencing a first recurrence of CDI after an initial course of fidaxomicin, vancomycin, or metronidazole.
Administer fidaxomicin in patients experiencing a first recurrence of CDI after an initial course of vancomycin or metronidazole.

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  • Management of recurrence (bezlotoxumab)

  • Management of recurrence (fecal microbiota transplantation)