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J Infect Dis. 2016 Jul 15;214(2):173-81. doi: 10.1093/infdis/jiv766. Epub 2016 Feb 8.

A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection.

Author information

1
Mayo Clinic, Rochester, Minnesota.
2
Miriam Hospital, Women's Medicine Collaborative, Providence, Rhode Island.
3
Emory University School of Medicine, Atlanta, Georgia.
4
Seres Therapeutics, Cambridge.
5
Massachusetts General Hospital, Boston, Massachusetts.

Abstract

BACKGROUND:

Patients with recurrent Clostridium difficile infection (CDI) have a ≥60% risk of relapse, as conventional therapies do not address the underlying gastrointestinal dysbiosis. This exploratory study evaluated the safety and efficacy of bacterial spores for preventing recurrent CDI.

METHODS:

Stool specimens from healthy donors were treated with ethanol to eliminate pathogens. The resulting spores were fractionated and encapsulated for oral delivery as SER-109. Following their response to standard-of-care antibiotics, patients in cohort 1 were treated with SER-109 on 2 consecutive days (geometric mean dose, 1.7 × 10(9) spores), and those in cohort 2 were treated on 1 day (geometric mean dose, 1.1 × 10(8) spores). The primary efficacy end point was absence of C. difficile-positive diarrhea during an 8-week follow-up period. Microbiome alterations were assessed.

RESULTS:

Thirty patients (median age, 66.5 years; 67% female) were enrolled, and 26 (86.7%) met the primary efficacy end point. Three patients with early, self-limiting C. difficile-positive diarrhea did not require antibiotics and tested negative for C. difficile at 8 weeks; thus, 96.7% (29 of 30) achieved clinical resolution. In parallel, gut microbiota rapidly diversified, with durable engraftment of spores and no outgrowth of non-spore-forming bacteria found after SER-109 treatment. Adverse events included mild diarrhea, abdominal pain, and nausea.

CONCLUSIONS:

SER-109 successfully prevented CDI and had a favorable safety profile, supporting a novel microbiome-based intervention as a potential therapy for recurrent CDI.

KEYWORDS:

Clostridium difficile infection; Clostridium difficile treatment; dysbiosis; microbiome; vancomycin-resistant Enterococcus

Comment in

PMID:
26908752
DOI:
10.1093/infdis/jiv766
[Indexed for MEDLINE]

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