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

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.

• Authors: Sahil Khanna, Darrell S Pardi, Colleen R Kelly, Colleen S Kraft, Tanvi Dhere, Matthew R Henn, Mary-Jane Lombardo, Marin Vulic, Toshiro Ohsumi, Jonathan Winkler, Christina Pindar, Barbara H McGovern, Roger J Pomerantz, John G Aunins, David N Cook, Elizabeth L Hohmann
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 214 Issue 2 Pg. 173-81 (07 15 2016) ISSN: 1537-6613 [Electronic] United States
• PMID: 26908752 (Publication Type: Journal Article)
• Copyright: © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected].

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biological Therapy (adverse effects, methods)
• Clostridioides difficile (growth & development)
• Clostridium Infections (prevention & control)
• Diarrhea (prevention & control)
• Female
• Gastrointestinal Microbiome
• Gastrointestinal Tract (microbiology)
• Humans
• Male
• Middle Aged
• Secondary Prevention (methods)
• Young Adult