Treatment of Clostridioides difficile Infection

Introduction

• Clostridioides difficile infection (CDI) is a significant healthcare concern, and its treatment and management are crucial to prevent recurrence and transmission, as recommended by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) 1, 2

Disease Classification

• Non-severe infection is classified as having a leukocyte count ≤15,000 cells/mL and a serum creatinine level <1.5 mg/dL, as defined by the IDSA 2
• Severe or fulminant cases may require different therapeutic approaches, including higher doses of vancomycin and possible addition of intravenous metronidazol, as recommended by the IDSA 2
• Markers of severe or fulminant CDI include leukocytosis, low serum albumin, and rising creatinine, and discontinuing any non-essential antibiotics is recommended if possible, as suggested by 3

Diagnostic Approach

• The recommended testing approach for patients suspected of having C. difficile colitis is a two-step protocol using nucleic acid amplification tests (NAATs) or glutamate dehydrogenase (GDH) assay as the initial screen, followed by toxin A/B detection for positive initial screens, with high diagnostic accuracy, as recommended by the IDSA and SHEA with a strength of evidence level of 1A 1, 2, 4
• Testing should be performed on patients with unexplained new-onset diarrhea, hospitalization >72 hours with diarrhea, recent healthcare facility admission, diarrhea after antibiotic exposure, or negative tests for other common enteropathogens, as recommended by the IDSA 5
• The following table summarizes the characteristics of different tests:

6, 1, 7

Treatment Options

• For initial non-severe episodes of CDI, the IDSA recommends vancomycin oral (125 mg four times a day for 10 days) and fidaxomicina oral (200 mg twice a day for 10 days) as first-line treatments, with strong evidence and high quality 2
• For mild-moderate CDI, treatment options include oral vancomycin or metronidazole, as recommended by the World Health Organization and the IDSA 8, 9
• For severe CDI, the first-line treatment is oral vancomycin, with higher doses considered in severe cases, as recommended by the IDSA 4
• For fulminant/complicated CDI, the recommended treatment is oral vancomycin plus intravenous metronidazole, with the option to add rectal vancomycin if ileus is present, as recommended by the IDSA and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 4, 8, 9
• Fidaxomicin is an alternative treatment option, particularly beneficial when antibiotics cannot be discontinued due to ongoing infection, as recommended by the IDSA 4, 2

Recurrence Treatment

• For the first recurrence, treatment options include vancomycin (if metronidazol was used initially), a prolonged and pulsed regimen of vancomycin, or fidaxomicina (if vancomycin was used initially), as recommended by the IDSA 2
• For subsequent recurrences, vancomycin taper and pulse regimen or fidaxomicin may be considered, as recommended by the IDSA 4, 2
• Fecal microbiota transplantation (FMT) should be considered for multiple recurrences, as recommended by the IDSA 8

Special Considerations

• Immunocompromised patients are at higher risk for recurrence and may benefit from adjunctive bezlotoxumab, as recommended by the IDSA with a strength of evidence level of 1A 10
• Elderly patients should be monitored for renal function during and after treatment due to increased risk of nephrotoxicity, as recommended by the American Geriatrics Society 9
• Implementing appropriate infection control measures, including isolation until 48 hours after diarrhea resolution, can help prevent the spread of C. difficile infection, as recommended by the Centers for Disease Control and Prevention (CDC) 2
• Reviewing and discontinuing unnecessary proton pump inhibitors (PPIs) may help reduce the risk of CDI and recurrence, as recommended by the American Gastroenterological Association and the World Health Organization (WHO) 8, 2
• Using antibiotics less frequently implicated with CDI may help reduce the risk of CDI, as recommended by the IDSA 8
• Discontinuing the inciting antibiotic as soon as possible can reduce the risk of recurrence, as recommended by the IDSA 2