What are the chances of Clostridioides difficile (C. diff) recurring a second or third time?

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Last updated: November 24, 2025View editorial policy

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Recurrence Risk of C. difficile Infection

After a first recurrence of CDI, 20-36% of patients will experience a second recurrence, and among those with a second recurrence, 40-65% will go on to have subsequent recurrences. 1

First Recurrence Risk

  • A first recurrence occurs in 6-23% of patients following an initial episode of CDI when observed for up to 8 weeks after discontinuation of treatment 1
  • The risk of recurrence increases incrementally with each subsequent episode 1

Second Recurrence Risk

  • Patients who experience a first recurrence have a 20-36% chance of developing a second recurrence after failing second-line therapy 1
  • This represents a substantial increase compared to the initial recurrence rate 1

Third and Subsequent Recurrence Risk

  • Among patients with a second recurrence, between 40-65% will experience subsequent (third or more) recurrences 1
  • This dramatically elevated risk underscores the progressive nature of recurrent CDI 1

Geographic Variation

The recurrence rates show some geographic variation:

  • In Taiwan, recurrence rates are 7.2-10.9%, which is similar to Korea (8.3%) and Japan (14%) 1
  • These rates are generally lower than those reported in Western populations 1

Pediatric Population

For children, the recurrence pattern differs:

  • Recurrent rates in pediatric CDI range from 2.6-30% 1
  • Second or subsequent recurrence rates in pediatric CDI are 14.5-32% 1

Clinical Implications

The escalating risk with each recurrence creates a critical clinical challenge. After the first recurrence, clinicians should recognize that approximately 1 in 4-5 patients will recur again, but after a second recurrence, nearly half of patients will continue to have ongoing episodes 1. This progressive pattern emphasizes the importance of aggressive management strategies after the first recurrence, including consideration of fidaxomicin, tapered vancomycin regimens, or fecal microbiota transplantation to break the cycle before patients reach the high-risk category of multiple recurrences 1.

Risk factors that amplify recurrence probability include age ≥65 years (RR 1.63), concurrent antibiotic use (RR 1.76), proton pump inhibitor use (RR 1.58), renal failure (RR 1.59), and immunocompromising conditions 1. The presence of multiple risk factors compounds the likelihood of recurrence 1.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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