What is the definition of recurrence in Clostridioides difficile (C. diff) infection?

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Last updated: March 7, 2025View editorial policy

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From the Guidelines

Recurrent Clostridioides difficile (C. diff) infection is typically defined as clinically significant diarrhea with a confirmatory positive test within 8 weeks of completing antibiotics for C. diff. This definition is based on the most recent guidelines from the American Gastroenterological Association (AGA) 1. The diagnosis of recurrent C. diff infection requires acute-onset, clinically significant, new-onset diarrhea and highly sensitive testing in combination with highly specific testing, plus improvement of diarrhea with C. diff-directed antibiotics.

Some key points to consider in the diagnosis and management of recurrent C. diff infection include:

  • The use of fecal microbiota-based therapies, such as conventional FMT, fecal microbiota live-jslm, and fecal microbiota spores live-brpk, may be considered in patients with recurrent C. diff infection, particularly after the second recurrence (third episode) or in select patients at high risk of recurrent C. diff infection 1.
  • The implementation considerations for the use of fecal microbiota-based therapies in immunocompetent adults with recurrent C. diff infection can be used in the mildly or moderately immunocompetent population, with the exception of using fecal microbiota spores live-brpk or fecal microbiota live-jslm 1.
  • Alternative therapies, such as vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab, may be considered in patients who are not interested in fecal microbiota-based therapies 1.
  • The risk of recurrent C. diff infection is higher in patients who receive other antibiotics during or after initial treatment of C. diff, have a defective humoral immune response against C. diff toxins, are of advancing age, or have increasingly severe underlying disease 1.
  • Fecal microbiota transplantation (FMT) has been shown to be effective in treating recurrent C. diff infection, with response rates ranging from 77% to 94% depending on the route of instillation 1.

Overall, the management of recurrent C. diff infection requires a comprehensive approach that takes into account the patient's individual risk factors, medical history, and treatment preferences. The goal of treatment is to prevent recurrence, reduce morbidity and mortality, and improve quality of life.

From the FDA Drug Label

CDI recurrence was defined as the development of a new episode of diarrhea associated with a positive stool test for toxigenic C. difficile following clinical cure of the presenting CDI episode.

The definition of recurrence in Clostridioides difficile (C. diff) infection is the development of a new episode of diarrhea associated with a positive stool test for toxigenic C. difficile following clinical cure of the presenting CDI episode 2.

From the Research

Definition of Recurrence in Clostridioides difficile (C. diff) Infection

  • Recurrence in C. diff infection refers to the reappearance of symptoms after a primary episode of infection has been treated 3, 4, 5, 6, 7.
  • The rate of recurrence is high, with 20-30% of patients experiencing recurrence after a primary infection and 60% after three or more episodes 5.
  • Recurrence is a major complication of C. diff infection and can be challenging to treat 3, 4, 5, 6, 7.

Factors Contributing to Recurrence

  • The use of antibiotics, such as metronidazole and vancomycin, can contribute to recurrence 4, 6.
  • The type of C. diff strain, such as non-North American Pulsed Field type 1 strains, can also affect the rate of recurrence 6.
  • Patient factors, such as age and underlying health conditions, may also play a role in recurrence 4, 5.

Treatment of Recurrence

  • Treatment of recurrence typically involves a different approach than the initial treatment, such as a vancomycin taper and pulse or fidaxomicin 3, 4, 5, 7.
  • Fecal microbiota transplantation and standardized microbiome restoration therapies have shown promise in reducing recurrence rates 5, 7.
  • Monoclonal antibodies, such as intravenous bezlotoxumab, may also be used to prevent recurrences 3, 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Recurrent Clostridioides difficile Infection: Current Clinical Management and Microbiome-Based Therapies.

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 2023

Research

Fidaxomicin versus vancomycin for Clostridium difficile infection.

The New England journal of medicine, 2011

Research

Therapeutics for Clostridioides difficile infection: molecules and microbes.

Expert review of gastroenterology & hepatology, 2023

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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