What is the management approach for a patient with a suspected or confirmed Clostridioides (C.) difficile infection?

Management of Clostridioides difficile Infection

Oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the first-line treatments for C. difficile infection, with fidaxomicin preferred due to lower recurrence rates. 1, 2, 3

Immediate Actions Upon Suspected or Confirmed CDI

Isolation and Infection Control

• Place the patient in a private room with a dedicated toilet immediately, even before test results return if suspicion is high 1
• Healthcare workers must wear gloves and gowns upon room entry and during all patient care 1
• Continue contact precautions for at least 48 hours after diarrhea resolution, or until discharge if facility CDI rates are high 1

Hand Hygiene Protocol

• Use soap and water for hand hygiene before and after patient contact—alcohol-based sanitizers do NOT kill C. difficile spores 4, 1
• Gloves must be removed at point of use, followed by thorough handwashing with soap and water 4

Antibiotic Management

• Stop the causative antibiotic immediately if clinically feasible 1, 2, 5
• If continued antibiotic therapy is necessary for another infection, switch to lower-risk agents including parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracyclines 2, 5
• Avoid high-risk antibiotics: clindamycin, third-generation cephalosporins, fluoroquinolones, and penicillins 1, 5

Diagnostic Approach

When to Test

• Test only symptomatic patients with ≥3 unformed stools in 24 hours 2
• Do NOT test asymptomatic patients—positive tests without diarrhea represent colonization, not infection 1, 2
• Do NOT perform test-of-cure after treatment completion 1, 2

Testing Methods

• Multistep approaches using PCR for toxin genes or single-step PCR on liquid stool samples have the highest sensitivity and specificity 2
• Testing should only be performed on unformed stools from symptomatic patients 1

Treatment by Disease Severity

Initial Episode - Nonsevere Disease

Preferred regimen: Fidaxomicin 200 mg orally twice daily for 10 days 2, 3, 6

Acceptable alternative: Oral vancomycin 125 mg four times daily for 10 days 1, 2

Last resort option (only when preferred agents unavailable): Metronidazole 500 mg orally three times daily for 10-14 days—but ONLY for patients with WBC ≤15,000 cells/μL and creatinine <1.5 mg/dL 2, 7, 8

Fulminant CDI

• Vancomycin 500 mg orally or by nasogastric tube four times daily PLUS intravenous metronidazole 500 mg every 8 hours 2
• Consider surgical consultation early for patients with peritonitis, toxic megacolon, or clinical deterioration 2

First Recurrence

Preferred regimen: Fidaxomicin 200 mg twice daily for 10 days, or fidaxomicin extended regimen 2, 6

Adjunctive therapy consideration: Bezlotoxumab 10 mg/kg IV once during antibiotic administration for high-risk patients (age >65 years, immunocompromised, severe initial CDI, or concomitant antibiotic use) 2, 8

Multiple Recurrences

• Fecal microbiota transplantation (FMT) is recommended for patients with multiple recurrent episodes who have received appropriate antibiotic therapy for at least three episodes 7, 8

Critical Supportive Measures

Medications to Avoid

• Do NOT use antimotility agents (loperamide, diphenoxylate) or antiemetics with antimotility effects—these prolong toxin retention and worsen outcomes 1
• Discontinue unnecessary proton pump inhibitors, as they increase CDI risk 5

Environmental Decontamination

• Use sodium hypochlorite (bleach) solutions for environmental cleaning in patient areas where C. difficile transmission is ongoing 4
• Daily to twice-daily disinfection of high-touch surfaces (including bed rails) and terminal cleaning with chlorine-based products reduces CDI rates by 45-85% 4
• Hydrogen peroxide vapor (HPV) disinfection is an effective alternative, reducing CDI rates from 1.0 to 0.4 cases per 1000 patient-days 4

Monitoring Treatment Response

Expected Timeline

• Clinical improvement should occur within 3-5 days of starting therapy 1, 2
• Monitor for resolution of fever, abdominal pain, and normalization of white blood cell count 1
• Treatment failure is defined as absence of response after 3-5 days 2

Recurrence Definition

• Recurrence is symptom reappearance within 8 weeks after treatment completion 1
• Risk factors for recurrence include continued non-C. difficile antibiotic use, concomitant acid suppression, older age, and severe underlying illness 1

Common Pitfalls to Avoid

• Do NOT treat asymptomatic carriers—eradication is not indicated as colonization is not a direct precursor for CDI 4, 1
• Do NOT use metronidazole as first-line therapy—current guidelines prioritize vancomycin or fidaxomicin 1, 7, 8
• Do NOT delay isolation pending test results—place patients on preemptive contact precautions if same-day results are unavailable 1
• Do NOT rely on alcohol-based hand sanitizer alone—C. difficile spores require mechanical removal with soap and water 4, 1
• Do NOT repeat testing within 7 days during the same episode 1

Pediatric Considerations (6 Months to <18 Years)

• For pediatric patients weighing ≥12.5 kg who can swallow tablets: fidaxomicin 200 mg orally twice daily for 10 days 3
• For younger or smaller children: fidaxomicin oral suspension dosed by weight (80-200 mg twice daily based on body weight) 3
• Testing is recommended only for children >12 months with prolonged diarrhea and risk factors 7