What is the recommended management for an initial episode of Clostridioides difficile infection, including treatment for severe disease, fulminant colitis, and recurrence?

Management of Clostridioides difficile Infection

For an initial episode of CDI, use either oral vancomycin 125 mg four times daily or fidaxomicin 200 mg twice daily for 10 days, with fidaxomicin preferred due to significantly lower recurrence rates. 1

Initial Episode Treatment

Non-Severe and Severe Disease

• Both vancomycin 125 mg orally four times daily and fidaxomicin 200 mg orally twice daily for 10 days are appropriate first-line options regardless of disease severity (non-severe: WBC ≤15,000 cells/mL and creatinine <1.5 mg/dL; severe: WBC ≥15,000 cells/mL or creatinine >1.5 mg/dL). 1
• Fidaxomicin demonstrates superior sustained cure rates (77%) compared to vancomycin (63-68%) and markedly lower recurrence (13-17% vs 24-27%). 2
• Vancomycin achieves clinical cure rates of 81-92% and is significantly more effective than metronidazole in severe disease (97% vs 76%). 1, 2

When Metronidazole May Be Considered

• Metronidazole 500 mg orally three times daily for 10 days should only be used for non-severe CDI in resource-limited settings where vancomycin or fidaxomicin are unavailable. 1
• Avoid repeated or prolonged metronidazole courses due to risk of cumulative and potentially irreversible neurotoxicity. 1, 2

Critical First Steps

• Discontinue the inciting antibiotic agent(s) as soon as possible, as this significantly influences recurrence risk. 1
• Avoid antiperistaltic agents and opiates in all CDI patients. 2

Fulminant CDI Management

Definition and Recognition

• Fulminant CDI is defined by hypotension or shock, ileus, or megacolon. 1, 2
• Supportive findings include WBC >15,000 cells/mL, serum creatinine ≥1.5 mg/dL, or albumin <30 g/L. 2

Treatment Regimen

• Vancomycin 500 mg orally (or via nasogastric tube) four times daily PLUS intravenous metronidazole 500 mg every 8 hours. 1, 2
• If ileus is present, add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as a retention enema. 1
• Vancomycin can be administered via nasogastric tube or trans-stoma in patients with ileostomy or colonic diversion. 2

Critical Pitfall

• Intravenous vancomycin is completely ineffective for CDI because it is not excreted into the colon. 2

Surgical Considerations

• Total abdominal colectomy with ileostomy should be performed for perforation, systemic inflammation not responding to antibiotics, toxic megacolon, or severe ileus. 2
• Surgery should be performed early, before the patient becomes critically ill. 2, 3

First Recurrence Treatment

Fidaxomicin 200 mg orally twice daily for 10 days is the preferred option for first recurrence. 1, 2

Alternative Regimens

• Vancomycin tapered and pulsed regimen: 125 mg four times daily for 10-14 days, then twice daily for 7 days, then once daily for 7 days, then every 2-3 days for 2-8 weeks. 1, 2
• Standard vancomycin 125 mg four times daily for 10 days if metronidazole was used for the initial episode. 1
• Extended-pulsed fidaxomicin: 200 mg twice daily for 5 days, then once every other day for 20 days. 1, 2

Adjunctive Therapy

• Bezlotoxumab 10 mg/kg intravenously as a single dose can be added during antibiotic therapy for patients at high risk of recurrence (age >65 years, immunocompromised, severe CDI, prior CDI episode). 1, 2
• The FDA warns that bezlotoxumab should be reserved for use when benefit outweighs risk in patients with congestive heart failure. 1

Second and Subsequent Recurrences

Treatment Options (in order of preference)

1. Fidaxomicin 200 mg twice daily for 10 days (standard or extended-pulsed regimen). 1, 2
2. Vancomycin tapered and pulsed regimen (as described above). 1, 2
3. Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days. 1, 2

Fecal Microbiota Transplantation

• FMT is strongly recommended after at least 2 recurrences (i.e., 3 total CDI episodes) that have failed appropriate antibiotic treatments. 1, 2
• FMT achieves resolution rates of 70-90% in clinical trials, with an 81% success rate compared to 31% for vancomycin alone in randomized trials. 1, 2

Treatment Monitoring and Response

• Clinical response typically requires 3-5 days after starting therapy; metronidazole may take up to 5 days. 2
• Do not perform a "test of cure" after treatment completion. 2
• Monitor stool frequency, consistency, and clinical parameters daily. 2

Special Considerations

Concomitant Antibiotic Use

• When patients require concomitant antibiotics for other infections during CDI treatment, fidaxomicin demonstrates superior cure rates compared to vancomycin (90.0% vs 79.4%). 4
• Concomitant antibiotic use is associated with lower cure rates (84.4% vs 92.6%) and more recurrences (24.8% vs 17.7%). 4

Proton Pump Inhibitors

• Although there is an epidemiologic association between PPI use and CDI, there is insufficient evidence to mandate PPI discontinuation solely as a CDI prevention measure. 1

Common Pitfalls to Avoid

• Never use metronidazole for severe or fulminant CDI—cure rates are significantly inferior to vancomycin. 1, 2
• Never administer intravenous vancomycin for CDI—it does not reach the colonic lumen. 2
• Do not delay surgical consultation in fulminant CDI. 2, 3
• Avoid repeated metronidazole courses due to neurotoxicity risk. 1, 2
• Do not use antiperistaltic agents or opiates. 2