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C. Diff Infection (CDI): From Diagnosis to Treatment


Clostridioides difficile is a gram-positive spore-forming and toxin-producing bacteria that can cause disease ranging from mild diarrhea to severe and even fatal colonic inflammation. It is spread via the fecal-oral route. This infection often occurs after antibiotic use, as antibiotics change the normal gut flora and allows this bacterium to grow and produce its toxins. It is common in hospital and long-term facility settings but is also commonly seen in the outpatient setting.  C. diff infection (CDI) can produce a wide range of symptoms from mild diarrheal disease to toxic megacolon which can be fatal; early recognition and identification is key


Can range from mild to severe, with initial symptoms caused by GI interruptions and include

  • Acute watery diarrhea (at least 3 unformed stools in 24 hours)
  • Crampy abdominal pain
  • Nausea
  • Vomiting
  • Bloody diarrhea (rarely)
  • Fever, abdominal distension and tenderness in severe disease

Risk Factors

  • Antibiotic use (especially clindamycin, cephalosporins, quinolones)
  • Medications that reduce gastric acid such as proton pump inhibitors
  • Older age
  • Prior infection with C. diff
  • Immunocompromised state
  • Hospitalization or resident in a long-term care facility

Differential Diagnosis

Infectious Diarrhea

  • Many organisms such as E. Coli, Salmonella, Shigella can cause diarrhea
    • Differentiate with stool cultures

Acute abdomen in severe disease

  • Careful evaluation as C. diff can present with abdominal distension and tenderness like acute abdomen

Irritable Bowel Syndrome

  • Crampy, chronic abdominal pain, bloating, altered bowel habits including diarrhea, constipation or alternating between both

Inflammatory Bowel Disease

  • Diarrhea (may be bloody), abdominal pain, low grade fever, fatigue, weight loss

Celiac Disease

  • Chronic or recurrent diarrhea, weight loss, abdominal distension or bloating with certain foods due to malabsorption


  • Definitive diagnosis
    • Send stool for C. Difficile toxin B
    • Testing done using PCR

Note: Reserve testing for appropriate clinical setting with high clinical suspicion due to high risk of false positive results


  • Stop offending agent if antibiotic-induced (when possible)
  • Can initiate treatment with high pre-test suspicion before confirmation with PCR

Initial episode of mild disease (leukocytosis with WBC <15,000 cells/mL and Creatinine of <1.5mg/dL)

  • Fidaxomicin should be first-line for treatment: 200mg orally twice a day for 10 days (IDSA)
  • Vancomycin 125mg orally four times a day for 10 days as second-line
  • If no access to Vancomycin or Fidaxomicin, Metronidazole orally 500mg three times a day for 10 days

Initial episode of severe disease (leukocytosis with WBC >15,000 cells/mL and Creatinine of >1.5mg/dL)

  • Fidaxomicin 200mg orally twice a day
  • Vancomycin 125mg four times a day for 10 days is second-line

Initial episode with fulminant disease (hypotension, shock, ileus, megacolon)

  • Vancomycin PO 500mg four times a day and per rectum (if ileus is present) plus IV Metronidazole 500mg three times a day


Complicated CDI Definition

  • Infection with hypotension requiring vasopressor therapy | Sepsis | Organ dysfunction | Mental status changes | WBC count >50,000 | Elevated lactate

Recurrent CDI

  • Recurrent CDI can occur 1-2 weeks after stopping treatment
  • First recurrence
    • Vancomycin 125mg orally four times a day for 10 days if metronidazole was used for the first episode or
    • Tapered and pulsed vancomycin regimen: 125mg four times a day for 10 days followed by 125mg two times a day for a week followed by once per day for a week then every 2 to 3 days for 2 to 8 weeks or
    • Fidamoxicin 200mg orally twice a day for 10 days if vancomycin was used for the first episode
  • Second recurrence
    • Tapered and pulsed Vancomycin regimen or
    • Fidamoxicin 200mg orally twice a day for 10 days

Note: NEVER use antidiarrheal drugs in CDI as this can lead to toxic megacolon | Surgery consult is needed if antibiotics fail in severe disease or in cases of complicated CDI | Consider fetal microbiota transplant if there is a third recurrence


  • Use of narrow spectrum antibiotics when possible
  • Hand washing with soap and water
    • Spores are not removed with ethyl alcohol-type hand sanitizer
  • Use contact precautions with gowns, gloves and use of disposable equipment when caring for an infected patient

Primary Sources – Learn More 

 American College of Gastroenterology: C. Difficile Infection

Infectious Disease Society of America Guideline

CDC: C. diff (Clostridioides difficile)

Fecal Microbiota Transplant for C. difficile – Oral Capsules or Colonoscopy?


  • Clostridium difficile infection (CDI) is a major cause of morbidity and mortality, particularly in the setting of recurrent CDI
  • Fecal microbiota transplant (FMT) is the most effective therapy for recurrent CDI
  • Uncontrolled studies suggest that colonoscopy is a better route of FMT delivery compared to oral
  • Kao et al. (JAMA, 2017) sought to compare the efficacy of FMT delivered by oral capsule versus colonoscopy


  • Noninferiority, unblinded, randomized trial of adult patients with recurrent CDI
  • Patients were randomly assigned to receive either capsule or colonoscopy
  • Primary outcome
    • Proportion of patients with recurrent CDI 12 weeks after FMT
  • Secondary outcomes
    • Serious and minor adverse events, changes in quality of life by the 36-Item Short Form Survey on a scale of 0 (worst) to 100 (best), and patient perception on a scale of 1 (not at all unpleasant) to 10 (extremely unpleasant) and satisfaction on a scale of 1 (best) to 10 (worst)


  • 57 patients randomized to the capsule group and 59 to the colonoscopy group
    • Mean age was 58 years; 68% were women
  • Prevention of recurrent CDI after a single treatment was achieved in 96.2% in both the capsule group (51/53) and the colonoscopy group (50/52), meeting the criterion for noninferiority
  • Rates of minor adverse events were 5.4% for the capsule group vs 12.5% for the colonoscopy group
  • A significantly greater proportion of participants receiving capsules rated their experience as “not at all unpleasant” (66% vs 44%; difference, 22% [95% CI, 3%-40%]; P = .01)
  • There was no significance between-groups in improvement in quality of life


  • FMT oral capsule was not inferior to delivery via colonoscopy over 12 weeks
  • Patients reported no difference in quality of life improvement between oral and colonoscopy but had fewer associated adverse events and lower reported levels of unpleasantness

Learn More – Primary Sources:

Effect of Oral Capsule– vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial