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.
M. J. Lombardo,
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