What is the treatment for a patient with a Clostridioides difficile (C. diff) toxin B gene positive result?

Treatment of C. difficile Toxin B Gene Positive Result

For a patient with a positive C. difficile toxin B gene test, oral vancomycin 125 mg four times daily for 10 days or oral fidaxomicin 200 mg twice daily for 10 days should be first-line therapy, with treatment selection based on disease severity assessment. 1, 2

Immediate Management Steps

Discontinue Precipitating Factors

• Stop the inciting antibiotic agent(s) immediately if clinically feasible, as continued antibiotic use significantly increases CDI recurrence risk 3
• If ongoing antibiotic therapy is required for another infection, switch to agents less frequently associated with CDI: parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline 3
• Discontinue proton pump inhibitors if not medically necessary, though evidence for this intervention remains limited 3, 2
• Avoid antimotility agents (loperamide, diphenoxylate) and opiates, as they may precipitate toxic megacolon 1, 2, 4

Assess Disease Severity

Non-severe CDI is defined by: 1, 2

• White blood cell count ≤15,000 cells/mL (or <15 × 10⁹/L)
• Serum creatinine <1.5 mg/dL
• Stool frequency <4 times daily
• No signs of severe colitis

Severe CDI is characterized by any of: 1, 2

• White blood cell count ≥15,000 cells/mL
• Serum creatinine >1.5 mg/dL (or rise >50% above baseline)
• Fever >38.5°C with rigors
• Hemodynamic instability or septic shock
• Signs of peritonitis or ileus
• Elevated serum lactate
• Pseudomembranous colitis on endoscopy
• Colonic distension or wall thickening on imaging

Treatment Algorithm by Disease Severity

Non-Severe CDI (Initial Episode)

Primary recommendation: Oral vancomycin 125 mg four times daily for 10 days OR oral fidaxomicin 200 mg twice daily for 10 days 1, 2, 4

Alternative (limited settings only): Oral metronidazole 500 mg three times daily for 10 days may be considered only in settings where access to vancomycin or fidaxomicin is limited 3, 1, 4

Critical caveat: Metronidazole is increasingly associated with treatment failures, particularly in patients >60 years, those with fever, hypoalbuminemia, peripheral leukocytosis, ICU stay, or abnormal abdominal CT imaging 1. Repeated or prolonged courses of metronidazole must be avoided due to risk of cumulative and potentially irreversible neurotoxicity 3, 1.

Severe CDI

Primary recommendation: Oral vancomycin 125 mg four times daily for 10 days 3, 2, 4

Alternative: Oral fidaxomicin 200 mg twice daily for 10 days 3

Vancomycin is considered superior to metronidazole in severe CDI based on higher clinical cure rates 3.

Fulminant/Complicated CDI

For fulminant disease (hypotension, shock, ileus, or megacolon): 3, 1

• Oral vancomycin 500 mg four times daily
• If ileus is present: Add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 1
• AND/OR: Intravenous metronidazole 500 mg every 8 hours 3

Surgical consultation: Obtain early surgical evaluation for patients with fulminant colitis 3. Colectomy should be considered for perforation, toxic megacolon, severe ileus, systemic inflammation with deteriorating clinical condition not responding to antibiotics, or serum lactate >5.0 mmol/L 2, 4.

Recurrent CDI Treatment

First Recurrence

Treat the same as the initial episode based on severity: metronidazole for non-severe (if vancomycin/fidaxomicin unavailable), vancomycin for severe 3, 1, 4

Second and Subsequent Recurrences

Primary recommendation: Oral vancomycin 125 mg four times daily for at least 10 days, with consideration of a taper/pulse strategy 3, 2, 4

Alternative: Oral fidaxomicin 200 mg twice daily for 10 days 3, 2

Fidaxomicin may be particularly useful for patients at high risk for recurrence (elderly patients with multiple comorbidities receiving concomitant antibiotics) 3, 1

Multiple Recurrences Unresponsive to Antibiotics

Fecal microbiota transplantation (FMT) is highly effective for patients with multiple CDI recurrences who have failed appropriate antibiotic treatments, with 70-90% success rates 3, 4

Adjunctive Therapy

Bezlotoxumab (monoclonal antibody against toxin B) may prevent recurrences, particularly in: 3

• Patients with CDI due to the 027 epidemic strain
• Immunocompromised patients
• Patients with severe CDI

Infection Control Measures

• Place patients in private rooms with dedicated toilet facilities when possible 3
• Use contact precautions with gown and gloves 3
• Hand hygiene with soap and water (not alcohol-based sanitizers, which do not kill C. difficile spores) 3
• Environmental cleaning with sporicidal disinfectants 3

Common Pitfalls to Avoid

• Do not use parenteral vancomycin for CDI—it is not excreted into the colon and is ineffective 4
• Do not perform "test of cure" after treatment; clinical improvement is the primary measure of success 3
• Do not delay surgery in severe cases waiting for antibiotic response; early colectomy improves outcomes in fulminant disease 4
• Do not use metronidazole for severe CDI or for repeated courses due to inferior efficacy and neurotoxicity risk 3, 1