P5576 - Antibiotic Exposure Is a Short- and Long-Term Risk for Recurrent Clostridioides difficile Infection Following Fecal Microbiota Transplantation

Dina Belhasan, MD¹, Nataliia Kuchma, MD, PhD², Jessica R.. Allegretti, MD, MPH³, Monika Fischer, MD, MS⁴, Alexander Khoruts, MD², Colleen R. Kelly, MD⁵, Byron Vaughn, MD, MS²
1University of Minnesota, Minneapolis, MN; 2University of Minnesota Medical Center, Minneapolis, MN; 3Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; 4Indiana University-Purdue University Indianapolis, Indianapolis, IN; 5Brigham and Women's Hospital, Providence, RI

Introduction: Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) after failure of standard therapies. Antibiotic exposure within 2-months post-FMT is a known risk factor for early recurrence. However, the timeline of antibiotics administration later in the post-FMT period and longer-term recurrence remains poorly studied. This study evaluates the association between antibiotic exposure at various intervals within 12 months post-FMT and rCDI.

Methods: Secondary analysis of a prospective cohort study included patients with history of rCDI treated with FMT between 7/1/19-11/29/23 across six centers. Follow-up occurred at 1, 2, 6, and 12 months, recording non-CDI antibiotic use and rCDI at each interval; exact dates were unavailable. The cohort was analyzed by follow-up time with individuals who had complete data for that interval. Following CDI recurrence, a participant was excluded from future timepoints. CDI recurrence was defined as laboratory positive testing (per local practice) and resumption of antibiotics for CDI.

Results: Of 701 patients in the cohort, 615 met the inclusion criteria, though not all individuals had follow-up at each timepoint. Most patients had 3 or more rCDI episodes prior to FMT (Table 1). Non-CDI antibiotic administration was associated with CDI recurrence at 1-, 2-, and 12-months, with a trend towards significance at 6-months (Table 2). Overall, the odds of developing CDI were 3-5 times higher following antibiotic exposure compared to no additional antibiotic exposure. After 1month, the risk of a spontaneous CDI recurrence (i.e., no additional antibiotic exposures) was < 5%. Between 6 and 12 months, all CDI recurrences occurred following one or more courses of non-CDI antibiotics.

Discussion: Antibiotic use post-FMT is a key driver of CDI recurrence. Prior studies have identified non-CDI antibiotic exposure as a risk factor for early recurrence (within 2 months). Our cohort replicates this finding, and also demonstrates that antibiotic exposure continues to be a risk for CDI recurrence for at least 1-year post FMT. Recall bias may be a limitation, as patients with recurrence may more readily remember antibiotic use than those without. Overall, our findings support caution in prescribing non-CDI antibiotics for at least a year following FMT for CDI.


Figure: Table 1: Patient characteristics


Figure: Table 2: Proportion of CDI recurrence at each follow-up time with and without additional non-CDI
antibiotic exposure.

Disclosures:
Dina Belhasan indicated no relevant financial relationships.
Nataliia Kuchma indicated no relevant financial relationships.
Jessica Allegretti: Abbvie – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Speaker, Speakers Bureau. Adiso – Consultant. Bristol Myer Squibb – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Speaker. Celltrion – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant. Ferring – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant. Finch – Consultant. Genentech – Advisory Committee/Board Member, Consultant. GlaxoSmithKline – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant. Iterative Scopes – Consultant. Janssen – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Speakers Bureau. Johnson & Johnson – Consultant, Grant/Research Support, Speaker. Merck – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Grant/Research Support. Pfizer – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Grant/Research Support. Roivant – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant. Roivant Adiso – Consultant. Seres Therapeutics – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant. Shattuck Labs – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant. TRXBio – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant. Vedanta – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant.
Monika Fischer: abbvie – Advisory Committee/Board Member. Criscot – DSMB chair. Eli Lilly – Advisor or Review Panel Member. Ferring – Advisory Committee/Board Member. Johnson and Johnson – Advisor or Review Panel Member, Speakers Bureau. seres – Advisor or Review Panel Member, Advisory Committee/Board Member.
Alexander Khoruts indicated no relevant financial relationships.
Colleen Kelly: Eli Lilly and Company – Advisory Committee/Board Member.
Byron Vaughn: Diasorin – Grant/Research Support. Health Delegates – Advisory Committee/Board Member. Kate Farms – Grant/Research Support. Takeda – Grant/Research Support.

Dina Belhasan, MD¹, Nataliia Kuchma, MD, PhD², Jessica R.. Allegretti, MD, MPH³, Monika Fischer, MD, MS⁴, Alexander Khoruts, MD², Colleen R. Kelly, MD⁵, Byron Vaughn, MD, MS². P5576 - Antibiotic Exposure Is a Short- and Long-Term Risk for Recurrent <i>Clostridioides difficile</i> Infection Following Fecal Microbiota Transplantation, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.