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
