Clostridioides difficile Infection — Adult

Key Points

• Test only symptomatic patients with clinically significant unformed stool or a compatible ileus syndrome.
• A positive NAAT can reflect colonization; interpret results within a diagnostic algorithm and clinical context.
• Do not perform routine test-of-cure after symptoms resolve.
• Fidaxomicin is preferred for initial nonfulminant CDI when available; oral vancomycin remains acceptable.
• Fulminant CDI is treated with high-dose enteral vancomycin plus IV metronidazole, with rectal vancomycin considered for ileus.
• Early surgery is essential when shock, megacolon, perforation, or progressive organ failure develops.
• Recurrent CDI management should prioritize strategies that reduce further recurrence, including fidaxomicin and selected microbiota-based therapy.
• Infection prevention requires contact precautions, environmental sporicidal cleaning, and handwashing with soap and water when caring for active CDI.

Algorithm

1. Confirm clinically significant diarrhea or compatible ileus and review laxatives and alternative causes.
2. Send stool testing using the institution's validated CDI algorithm; do not test formed stool.
3. Classify as nonsevere, severe, or fulminant using clinical physiology and laboratory markers.
4. Stop unnecessary inciting antibiotics and begin fidaxomicin or oral vancomycin for nonfulminant disease.
5. For fulminant disease, use high-dose enteral vancomycin plus IV metronidazole and add rectal vancomycin when ileus is present.
6. Obtain abdominal imaging and early surgical consultation for distension, shock, rising lactate, or organ failure.
7. For recurrence, choose fidaxomicin, vancomycin taper, bezlotoxumab, or microbiota-based therapy according to recurrence history and risk.
8. Implement isolation and environmental cleaning and reassess antibiotic stewardship to prevent future episodes.

Clinical Synopsis & Reasoning

Typical CDI causes at least three unformed stools in 24 hours with abdominal cramping, fever, leukocytosis, or rising creatinine. Severe colitis can produce ileus, toxic megacolon, hypotension, lactic acidosis, kidney injury, and perforation; diarrhea may diminish when ileus develops, so absence of stool does not reassure a deteriorating patient. Test only patients with clinically significant new diarrhea not explained by laxatives or another obvious cause. Laboratories use nucleic-acid amplification tests, toxin immunoassays, or multistep algorithms. NAAT is highly sensitive for toxigenic organisms but can detect colonization, making diagnostic stewardship essential. Do not test for cure because colonization and positive assays can persist after symptoms resolve. Classify nonsevere and severe disease using leukocyte count and creatinine while recognizing that fulminant disease is defined clinically by hypotension, shock, ileus, or megacolon. Evaluate severe abdominal distension or systemic toxicity with cross-sectional imaging and surgical consultation. Consider other causes of diarrhea including medications, enteral feeding, inflammatory bowel disease, ischemic colitis, and other infections.

Treatment Strategy & Disposition

Stop the inciting antibiotic when feasible and avoid unnecessary acid suppression or antimotility drugs in severe colitis. The 2021 IDSA/SHEA focused update prefers fidaxomicin over standard-course vancomycin for an initial nonfulminant episode when resources permit because sustained response is better; oral vancomycin remains acceptable. Fidaxomicin is also preferred for many recurrences, while tapered-pulsed oral vancomycin is an option, especially after a first recurrence. Multiple recurrences can be treated with microbiota-based therapy or fecal microbiota transplantation according to current regulatory, safety, and product availability frameworks. Bezlotoxumab can reduce recurrence in selected high-risk patients, although heart failure history requires caution. Fulminant CDI is treated with oral or nasogastric vancomycin 500 mg four times daily plus IV metronidazole, adding rectal vancomycin when ileus prevents distal delivery. Obtain early colorectal surgical input for worsening shock, rising lactate, megacolon, perforation, or organ failure. Surgical options include subtotal colectomy or selected diverting-loop ileostomy with colonic lavage at experienced centers.

Epidemiology / Risk Factors

• Antibiotic exposure is the dominant modifiable risk factor, particularly with broad-spectrum and prolonged therapy.
• Advanced age, hospitalization, long-term care residence, immunocompromise, inflammatory bowel disease, and prior CDI increase risk.
• Recurrence occurs frequently after a first episode and becomes more likely after each subsequent recurrence.
• Asymptomatic colonization is common in health care settings and explains why indiscriminate molecular testing overdiagnoses infection.
• Community-associated CDI occurs even without recent hospitalization and should remain in the differential of compatible diarrhea.

Investigations

Severity (Typical Adult Criteria)

Pharmacology

Prognosis / Complications

• Most nonfulminant episodes respond to appropriate oral therapy.
• Recurrence, rather than initial treatment failure, is the major long-term challenge.
• Fulminant colitis has high mortality, especially when surgical consultation is delayed until irreversible shock develops.
• Kidney injury, marked leukocytosis, hypoalbuminemia, immunocompromise, and advanced age predict a more complicated course.
• Microbiota restoration therapies have improved options for patients with repeated recurrence.

Patient Education / Counseling

• Take the prescribed CDI medication exactly as directed and do not self-treat recurrent diarrhea with leftover antibiotics.
• Wash hands with soap and water after using the bathroom and before food preparation while symptomatic.
• Clean high-touch bathroom surfaces with a sporicidal product suitable for C. difficile.
• Seek urgent care for severe abdominal swelling, inability to pass stool or gas, fever with worsening pain, fainting, or reduced urine output.
• Tell future clinicians about prior CDI when antibiotics are being considered so unnecessary or high-risk antibiotic exposure can be minimized.

Notes

The main diagnostic challenge in CDI is distinguishing infection from colonization. Testing is powerful only when applied to the right patient. The main therapeutic challenge is preventing recurrence without missing the smaller group progressing to fulminant colitis. Fidaxomicin has become the preferred nonfulminant therapy when accessible, while fulminant disease still relies on high-dose enteral vancomycin, IV metronidazole, aggressive supportive care, and early surgical involvement. Antibiotic stewardship and environmental spore control are integral parts of treatment rather than separate infection-control tasks.

References

1. SHEA/IDSA 2021 Focused Update for Management of Clostridioides difficile Infection — Link