757. Vancomycin-resistant enterococcal (VRE) titers diminish among patients with recurrent Clostridium difficile infection after administration of SER-109, a novel microbiome agent
Session: Poster Abstract Session: All Things Microbiome
Friday, October 9, 2015
Room: Poster Hall
Background: VRE infections are a worldwide problem due to increasing prevalence, lack of effective therapies and modest impact of infection control policies. A leading risk factor for VRE is prior antibiotic use, which disrupts the healthy microbiome. In a study of patients with recurrent Clostridium difficile infection (RCDI), we assessed the prevalence of VRE before and after administration of SER-109, a novel microbiome-based biologic agent for the prevention of RCDI.

Methods: SER-109 is an ecology of bacterial spores enriched from stool from healthy, screened donors. The efficacy and safety of SER-109 was evaluated for prevention of RCDI in an open-label study of 30 outpatients with ≥ 3 episodes of CDI in the past 12 months who had responded to standard antibiotics. During 8 weeks following SER-109, 26/30 patients (87%) had no evidence of C. difficile related diarrhea, and 3 patients with transient diarrhea had resolution of symptoms without treatment intervention, for an overall clinical resolution of 96.7%. To determine the prevalence of VRE, baseline and week 4 stools were plated to Enterococcosel medium with 8 ug/mL vancomycin and titers of VRE (cfu/g) were determined.

Results: Of the 30 patients (67% female, mean age 66.5 years), 25 (83.3%) had been treated with vancomycin for RCDI. At baseline, 8 of 29 patients (27.6%) had VRE (ie, E. faecium) and in all 8 VRE titers decreased by 2-6 logs (to below the limit of detection) after SER-109. Other evidence of a remodeling of the microbiome by SER-109 includes a shift in the proportions of Enterobacteriaceae to a predominance of E. coli, and an increase in microbiome diversity detected via genomics analysis (Chao-1 diversity index of 24±8 at baseline shifted to 31±5 at 8 weeks, p < 0.01). Engraftment of species from SER-109 and augmentation (outgrowth) of non-spore forming bacteria (Bacteroides and Parabacteroides) not found in SER-109 were also observed. 

Conclusion: VRE colonization was commonly observed among outpatients with RCDI. SER-109, an ecology of bacterial spores, was associated with significantly diminished VRE colonization. Restoration of the gut microbiome may be a novel infection control measure to provide colonization resistance against drug-resistant pathogens.

Mary-Jane Lombardo, PhD1, Marin Vulic, PhD1, Toshi Ohsumi, PhD1, David Cook, PhD1, Matthew Henn, PhD1, Colleen Kraft, MD2, Sahil Khanna, MBBS, MS3, Darrell Pardi, MD, MS3 and Elizabeth Hohmann, MD, FIDSA4, (1)Seres Therapeutics, Inc, Cambridge, MA, (2)Emory University School of Medicine, Atlanta, GA, (3)Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, (4)Infectious Diseases, Massachusetts General Hospital, Boston, MA

Disclosures:

M. J. Lombardo, Seres Therapeutics: Employee , Salary

M. Vulic, Seres Therapeutics: Employee , Salary

T. Ohsumi, Seres Therapeutics, Inc.: Employee and Shareholder , Salary

D. Cook, Seres Therapeutics Inc: Employee and Shareholder , Salary

M. Henn, Seres Therapeutics: Employee and Shareholder , Salary

C. Kraft, None

S. Khanna, None

D. Pardi, None

E. Hohmann, None

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.