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. 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

Sahil Khanna  1 , Darrell S Pardi  1 , Colleen R Kelly  2 , Colleen S Kraft  3 , Tanvi Dhere  3 , Matthew R Henn  4 , Mary-Jane Lombardo  4 , Marin Vulic  4 , Toshiro Ohsumi  4 , Jonathan Winkler  4 , Christina Pindar  5 , Barbara H McGovern  4 , Roger J Pomerantz  4 , John G Aunins  4 , David N Cook  4 , Elizabeth L Hohmann  5
Affiliations

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

Sahil Khanna et al. J Infect Dis. .

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.

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Comment in

  • Fecal Microbiota Transfer 2.0.
    Vehreschild MJ, Cornely OA. Vehreschild MJ, et al. J Infect Dis. 2016 Jul 15;214(2):169-70. doi: 10.1093/infdis/jiv768. Epub 2016 Feb 8. J Infect Dis. 2016. PMID: 26908719 Free PMC article. No abstract available.
  • Critical Microbiological View of SER-109.
    Lagier JC, Cadoret F, Raoult D. Lagier JC, et al. J Infect Dis. 2017 Jan 1;215(1):161-162. doi: 10.1093/infdis/jiw489. Epub 2016 Oct 20. J Infect Dis. 2017. PMID: 28077591 No abstract available.
  • Reply to Lagier et al.
    Khanna S, Button JE, Lombardo MJ, Vulic M, Henn MR, Cook DN, Pomerantz RJ, Hohmann EL. Khanna S, et al. J Infect Dis. 2017 Jan 1;215(1):162-164. doi: 10.1093/infdis/jiw490. Epub 2016 Oct 20. J Infect Dis. 2017. PMID: 28077592 No abstract available.