What is the management approach for Clostridioides difficile (C. diff) diarrhea?

Management of Clostridioides difficile Diarrhea

Oral vancomycin 125 mg four times daily for 10 days or oral fidaxomicin 200 mg twice daily for 10 days are the first-line treatments for C. difficile infection, regardless of severity, and metronidazole should no longer be used as initial therapy due to inferior efficacy. 1, 2

Immediate Initial Steps

Discontinue the inciting antibiotic immediately if clinically feasible, as continued antibiotic use significantly increases recurrence risk. 3, 1 If ongoing antibiotic therapy is essential for another infection, switch to agents less associated with CDI: parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline. 3

Avoid antimotility agents (loperamide) and opiates as they may worsen outcomes and precipitate toxic megacolon. 1, 2

Consider discontinuing proton pump inhibitors if not medically necessary, though evidence for this intervention remains limited. 3, 1

Treatment Based on Disease Severity

Non-Severe CDI

Defined by: WBC ≤15,000 cells/mL, serum creatinine <1.5 mg/dL, stool frequency <4 times daily, no signs of severe colitis. 1, 2

• Oral vancomycin 125 mg four times daily for 10 days 1, 2, 4
• OR oral fidaxomicin 200 mg twice daily for 10 days 1, 2, 5
• Metronidazole 500 mg three times daily may only be considered when vancomycin or fidaxomicin are unavailable, but this represents suboptimal therapy. 2

Severe CDI

Defined by: WBC ≥15,000 cells/mL, serum creatinine >1.5 mg/dL, fever, or signs of severe colitis. 1, 2

• Oral vancomycin 125 mg four times daily for 10-14 days 1, 2
• Vancomycin demonstrates superior efficacy compared to metronidazole in severe disease. 2

Fulminant CDI

Defined by: hypotension, shock, ileus, toxic megacolon, or colonic perforation. 1, 2

• Oral vancomycin 500 mg four times daily 1, 2
• PLUS intravenous metronidazole 500 mg every 8 hours 1, 2
• PLUS rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema if ileus present 3, 2
• Obtain immediate surgical consultation as colectomy may be life-saving. 3, 2

Management of Recurrent CDI

First Recurrence

• Oral vancomycin 125 mg four times daily for 10 days (especially if metronidazole was used initially) 1, 2
• OR oral fidaxomicin 200 mg twice daily for 10 days (especially if vancomycin was used initially) 1, 2
• OR vancomycin tapered and pulsed regimen 2

Second or Subsequent Recurrence

After two recurrences, the risk of further relapses exceeds 50%. 6

• Vancomycin tapered and pulsed regimen 2
• OR vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 2
• OR fidaxomicin 200 mg twice daily for 10 days 2
• OR fecal microbiota transplantation (FMT) 3, 2

Fecal Microbiota Transplantation

FMT is strongly recommended for patients with multiple recurrences who have failed appropriate antibiotic treatments, with cure rates of 80-100% when administered via the colon. 3, 2 The landmark van Nood trial demonstrated 81% sustained resolution after FMT versus 27% with vancomycin alone (P <0.001). 2

• FMT should only be considered after recurrence following resolution of an episode treated with appropriate antimicrobials for at least 10 days. 3
• FMT should NOT be used as initial therapy for CDI. 3
• If first FMT fails, repeat FMT demonstrates excellent success rates. 3
• Follow-up for at least 8 weeks post-FMT is appropriate to assess efficacy and adverse events. 3

Infection Control Measures

Hand hygiene with soap and water is essential as alcohol-based sanitizers do not kill C. difficile spores. 3, 2

Implement contact precautions until resolution of diarrhea (passage of formed stool for at least 48 hours). 3

Place patients in private rooms with dedicated toilet facilities when possible; environmental disinfection with sporicidal agents is critical. 3, 2

Monitoring and Special Populations

Monitor for treatment response by assessing decreased stool frequency and improved consistency after 3 days of treatment. 1 Treatment failure is defined as absence of response after 3-5 days. 1

In patients >65 years of age, monitor renal function during and after treatment as nephrotoxicity risk is increased, even in those with normal baseline renal function. 4 Clinically significant serum vancomycin concentrations can occur with oral therapy in patients with inflammatory intestinal mucosa. 4

Critical Pitfalls to Avoid

Never use metronidazole as first-line therapy for initial CDI episodes, and avoid repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity. 2

Do not perform "test of cure" after CDI treatment, and do not test asymptomatic patients as laboratory tests cannot distinguish colonization from infection. 2

Remember that oral vancomycin is NOT systemically absorbed and is only effective for intestinal C. difficile infection; parenteral vancomycin is ineffective for CDI. 4