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

SUMMARY:

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

Symptoms

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
• Anorexia
• Nausea
• Vomiting
• Bloody diarrhea (rarely)
• Fever, abdominal distension and tenderness in severe disease

Risk Factors

• Antibiotic use (especially clindamycin, cephalosporins, quinolones and penicillins)
• 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

Diagnosis

• Definitive diagnosis
  • Send stool for C. Difficile toxin B. Only liquid stool should be sent
  • If patient has ileus and there is concern for C. diff infection then rectal swab for culture or toxin assay is recommended
  • Testing typically done using PCR

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

Treatment

• 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 to 14 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 for 10 days
• Vancomycin 125mg four times a day for 10 days as 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 every 8 hours

Complications

Fulminant CDI Definition (previously termed complicated C. diff infection)

• Shock, ileus, toxic megacolon

Recurrent CDI

• Recurrent CDI can occur 1-2 weeks after stopping treatment
• First recurrence
  • Fidaxomicin 200mg orally twice a day for 10 days or
  • Fidaxomicin 200 mg orally twice daily for 5 days, followed by once every other day for 20 days or
  • Vancomycin 125mg orally four times a day for 10 days 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
  • Bezlotoxumab 10 mg/kg intravenously, given once in addition to one of the above antibiotic courses
• Second recurrence
  • Fidaxomicin in a standard or extended pulse regimen (see above) or
  • Vancomycin in a tapered and pulsed regimen (see above) or
  • Vancomycin 125mg orally four times daily for 10 days followed by Rifaximin 400 mg orally 3 times daily for 20 days
  • Bezlotoxumab (Zinplava) 10 mg/kg intravenously, given once in addition to one of the above antibiotic courses

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

Prevention

• 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?

BACKGROUND AND PURPOSE:

• 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

METHODS:

• 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)

RESULTS:

• 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

CONCLUSION:

• 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