What is my estimated risk of Clostridioides (C.) difficile infection recurrence with antibiotic use?

Risk of C. difficile Infection Recurrence with Antibiotic Use

Antibiotic use significantly increases the risk of C. difficile infection recurrence, with approximately 25% of patients treated for CDI experiencing at least one additional episode. 1

Understanding the Risk of Recurrence

The risk of C. difficile infection recurrence with antibiotic use can be quantified as follows:

• Approximately 25% of patients treated for CDI with vancomycin can be expected to experience at least one additional episode 1
• For patients with a first CDI recurrence, the risk of a second recurrence is:
  • 19.7% when treated with fidaxomicin
  • 35.5% when treated with a standard 10-day course of vancomycin 1

Risk Factors for CDI Recurrence

Several factors increase the risk of recurrence when antibiotics are used:

• Administration of other antibiotics during or after initial treatment of CDI 1
• Defective humoral immune response against C. difficile toxins 1
• Advanced age 1
• Increasingly severe underlying disease 1
• Continued use of proton pump inhibitors 1

Antibiotic-Specific Risk

The risk of CDI recurrence varies by antibiotic class:

• Highest risk antibiotics:
  • Clindamycin (adjusted odds ratio: 35.31)
  • Fluoroquinolones (adjusted odds ratio: 30.71)
  • Cephalosporins (adjusted odds ratio: 19.02)
  • Beta-lactam/beta-lactamase inhibitor combinations (adjusted odds ratio: 9.87) 2

Duration-Dependent Risk

Each additional day of certain antibiotics increases the risk of CDI:

• Each day of β-lactam/β-lactamase inhibitors, third- and fourth-generation cephalosporins, and carbapenems increases the risk of CDI by over 2% 3

Strategies to Reduce Recurrence Risk

To minimize the risk of recurrence when antibiotics are necessary:

1. Choose optimal CDI treatment:

   • Fidaxomicin is preferred over vancomycin for recurrent CDI episodes due to lower recurrence rates (19.7% vs 35.5%) 1
   • For first recurrence, consider fidaxomicin 200 mg twice daily for 10 days or an extended-pulsed regimen 2

2. Consider adjunctive therapy:

   • Bezlotoxumab may be considered as a co-intervention with standard antibiotics for patients with recurrent CDI within the last 6 months 1
   • For multiple recurrences, fecal microbiota transplantation is recommended after failure of appropriate antibiotic treatments 1, 2

Clinical Pitfalls to Avoid

• Don't use metronidazole for recurrent CDI: Initial and sustained response rates are lower than for vancomycin, and there's potential for cumulative neurotoxicity with long-term use 1
• Don't ignore antibiotic stewardship: Preventing recurrence should focus on reducing overall antibiotic use and shortening exposure rather than just avoiding specific agents 3
• Don't continue unnecessary PPIs: Continued use of proton pump inhibitors is associated with increased risk of recurrence 1, 2

Special Considerations

For patients who require antibiotics for other infections during or shortly after CDI treatment:

• These patients have a higher risk of recurrence 1
• Some clinicians prolong CDI treatment until after other antibiotic regimens are completed 1
• Lower doses of vancomycin (e.g., 125 mg once daily) may be sufficient for prevention during necessary antibiotic therapy 1

In summary, antibiotic use significantly increases the risk of C. difficile recurrence, with approximately one-quarter of patients experiencing at least one recurrence. The risk varies by antibiotic class, duration, and patient factors, with recurrence rates ranging from approximately 20% with optimal treatment to over 35% with standard therapy.