The presence of Clostridioides difficile in faeces before and after faecal microbiota transplantation and its relation with recurrent C. difficile infection and the gut microbiota in a Dutch cohort

Bas Groenewegen; Emilie van Lingen; Artemiy Kovynev; Alexander J van den Berg; Eric K L Berssenbrugge; Ingrid M J G Sanders; Joffrey van Prehn; Els van Nood; Abraham Goorhuis; Ed J Kuijper; Wiep Klaas Smits; Maria Wiese; Josbert J Keller; Quinten R Ducarmon; Elisabeth M Terveer; Study Group of the Netherlands Donor Feces Bank

doi:10.1016/j.cmi.2024.12.003

The presence of Clostridioides difficile in faeces before and after faecal microbiota transplantation and its relation with recurrent C. difficile infection and the gut microbiota in a Dutch cohort

Clin Microbiol Infect. 2024 Dec 9:S1198-743X(24)00589-5. doi: 10.1016/j.cmi.2024.12.003. Online ahead of print.

Authors

Bas Groenewegen¹, Emilie van Lingen¹, Artemiy Kovynev², Alexander J van den Berg³, Eric K L Berssenbrugge³, Ingrid M J G Sanders⁴, Joffrey van Prehn⁵, Els van Nood⁶, Abraham Goorhuis⁷, Ed J Kuijper⁵, Wiep Klaas Smits², Maria Wiese⁸, Josbert J Keller⁹, Quinten R Ducarmon², Elisabeth M Terveer¹⁰; Study Group of the Netherlands Donor Feces Bank

Affiliations

¹ Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
² Center for Microbiome Analyses and Therapeutics, Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands.
³ Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands.
⁵ Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands; Center for Microbiome Analyses and Therapeutics, Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands.
⁶ Department of Medical Microbiology and Infectious Diseases and Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
⁷ Department of Internal Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands.
⁸ Center for Microbiome Analyses and Therapeutics, Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands; Department of Microbiology and Systems Biology, Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands.
⁹ Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands; Department of Gastroenterology and Hepatology, Haaglanden Medical Center, Den Haag, The Netherlands.
¹⁰ Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands; Center for Microbiome Analyses and Therapeutics, Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: [email protected].

PMID: 39662821
DOI: 10.1016/j.cmi.2024.12.003

Abstract

Objectives: The objectives of this study are to investigate the presence of Clostridioides difficile in faeces of patients with recurrent C. difficile infection (rCDI) before and after faecal microbiota transplantation (FMT) and to identify risk factors for faecal C. difficile and C. difficile infection (CDI) recurrence.

Methods: n = 83 faecal sample triads (pre-FMT [∼1 day], post-FMT [∼3 weeks], and a corresponding FMT donor sample), and n = 22 long-term (∼1-3 years) follow-up faecal samples were collected from FMT-treated patients. The presence of C. difficile in faeces was assessed by enrichment broth culture and PCR (tcdB gene) and associated with patient characteristics, FMT outcome, duration of pre-FMT vancomycin, FMT donor, post-FMT antibiotic use, and faecal microbiota composition (shotgun metagenomics).

Results: The FMT cure rate for rCDI was 92.8% (77/83), with six early CDI recurrences (<2 months post-FMT). Toxigenic C. difficile was cultured in 27.7% (23/83) of all patients post-FMT, 23.4% (18/77) of patients cured 2 months post-FMT, and 13.6% (3/22) at long-term follow-up. Early CDI recurrence (n = 6) was associated with positive C. difficile culture post-FMT (21.7% [5/23] vs. 1.7% [1/60], p 0.01), post-FMT antibiotics (30.0% [3/10] vs. 4.6% [3/65], p 0.03), and a short course of pre-FMT vancomycin (median 6.0 days, IQR [5-12] vs. 18 days, IQR [10.8-29], p < 0.05). Additionally, positive C. difficile culture directly pre-FMT was associated with a short course of pre-FMT vancomycin (median 9 days IQR [5-18] vs. 17 days, IQR [10-29.2], p 0.04). Gut microbiota analyses did not reveal signatures associated with C. difficile culture result, despite statistically non-significant trends in relative abundances of the Enterobacteriaceae family, and Dorea, Roseburia, and Clostridiales species.

Discussion: Although eradication of C. difficile is not required for clinical cure of rCDI by FMT, it is associated with reduced prevalence of early CDI recurrence, as are the full completion of pre-FMT vancomycin (at least 10 days) and avoiding post-FMT antibiotics.

Keywords: Carriage; Clostridioides difficile; Colonisation; Eradication; FMT; Faecal microbiota transplantation; Gut microbiome; Gut microbiota; Pre-treatment; rCDI.