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

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

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143 Scopus citations

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 × 109 spores), and those in cohort 2 were treated on 1 day (geometric mean dose, 1.1 × 108 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.

Original languageEnglish (US)
Pages (from-to)173-181
Number of pages9
JournalJournal of Infectious Diseases
Volume214
Issue number2
DOIs
StatePublished - Jul 15 2016

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Keywords

  • Clostridium difficile infection
  • Clostridium difficile treatment
  • Dysbiosis
  • Microbiome
  • Vancomycin-resistant Enterococcus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Medicine(all)
  • Infectious Diseases

Cite this

Khanna, S., Pardi, D. S., Kelly, C. R., Kraft, C. S., Dhere, T., Henn, M. R., Lombardo, M. J., Vulic, M., Ohsumi, T., Winkler, J., Pindar, C., McGovern, B. H., Pomerantz, R. J., Aunins, J. G., Cook, D. N., & Hohmann, E. L. (2016). A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection. Journal of Infectious Diseases, 214(2), 173-181. https://doi.org/10.1093/infdis/jiv766