TY - JOUR
T1 - A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection
AU - Khanna, Sahil
AU - Pardi, Darrell S.
AU - Kelly, Colleen R.
AU - Kraft, Colleen S.
AU - Dhere, Tanvi
AU - Henn, Matthew R.
AU - Lombardo, Mary Jane
AU - Vulic, Marin
AU - Ohsumi, Toshiro
AU - Winkler, Jonathan
AU - Pindar, Christina
AU - McGovern, Barbara H.
AU - Pomerantz, Roger J.
AU - Aunins, John G.
AU - Cook, David N.
AU - Hohmann, Elizabeth L.
N1 - Publisher Copyright:
© 2016 The Author 2016.
PY - 2016/7/15
Y1 - 2016/7/15
N2 - 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.
AB - 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.
KW - Clostridium difficile infection
KW - Clostridium difficile treatment
KW - Dysbiosis
KW - Microbiome
KW - Vancomycin-resistant Enterococcus
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U2 - 10.1093/infdis/jiv766
DO - 10.1093/infdis/jiv766
M3 - Article
C2 - 26908752
AN - SCOPUS:84977079273
SN - 0022-1899
VL - 214
SP - 173
EP - 181
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -