Background: Clostridioides difficile infection (CDI) has emerged as a prevalent and recurrent antibiotic-associated infection. Fecal microbiota transplantation (FMT) is the most effective treatment for recurrent CDI (rCDI). Despite high success rates, FMT is ineffective in 5-20% of cases. Factors associated with failure have not been clearly defined. We seek to better understand factors predictive of FMT failure. Methods: A retrospective chart review was conducted on adult patients who were screened at the Complicated C. difficile Clinic at the University of Virginia Health System and received FMT for rCDI between 2013 and 2022. Primary outcome was failure of FMT, defined as either rCDI or all-cause death within one year. Results: 240 patients underwent FMT: 70.4% were female, median age was 68, and median episodes of CDI was 4. 24.6% experienced failure within the year (18.3% had rCDI and 7.1% died). Age 70 or older (p=0.007), male sex (p=0.013), ≥4 episodes of CDI (p=0.010), hypertension (p=0.010), diabetes mellitus (p=0.002), malignancy (p=0.034), high thyroid-stimulating hormone (p=2.696x10-5), anemia (p=0.002), and low zinc (p=0.025) were significantly associated with FMT failure on univariate analysis; age 70 or older (OR=2.66 [1.29-5.67]), ≥4 episodes of CDI (OR=3.13 [1.47-7.09]), and diabetes mellitus (OR=2.82 [1.25-6.50]) persisted to be associated with failure on multivariate analysis. Conclusions: Our study shows that FMT remains an effective treatment for rCDI. We highlight several factors associated with FMT failure, such as older age, ≥4 episodes of CDI, anemia, elevated TSH, and low zinc, and the need for additional research to clearly define causality.

CAW participated in the medical advisory board of SER-109 Seres Therapeutics and is a site PI of ROAR (Ferring Pharma). JHS and BWB are site co-I for ROAR (Ferring Pharma).

This study was funded by the National Institutes of Health [grant numbers K08AG064151 (JHS) and R01AI AI145322 (CAW)].

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Institutional Review Board at the University of Virginia gave ethical approval for this work (IRB-HSR#23045, Fecal Microbiota Transplantation). As this is a descriptive study of patients who are undergoing treatment recommended by IDSA guidelines, no hazardous procedures or chemicals are involved. The privacy rights of human subjects have been observed.

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All data produced in the present study are available upon reasonable request to the authors.