Robert Orenstein,1 Erik Dubberke,2 Robert Hardi,3 Arnab Ray,4 Kathleen Mullane,5 Darrell S. Pardi,6 and Mayur S. Ramesh7; for the PUNCH CD Investigatorsa
1Division of Infectious Diseases, Mayo Clinic–Arizona, Phoenix; 2Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; 3Chevy Chase Clinical Research, Capital Digestive Care, Maryland; 4Ochsner Clinic, New Orleans, Louisiana; 5Section of Infectious Diseases and Global Health, University of Chicago Medicine, Illinois; 6Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; and 7Henry Ford Hospital System, Detroit, Michigan
Managing recurrent Clostridium difﬁcile infection (CDI) presents a signiﬁcant challenge for clinicians and patients. Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent CDI, yet availability of a standardized, safe, and effective product has been lacking. Our aim in this study was to assess the safety and effectiveness of RBX2660 (microbiota suspension), a commercially prepared FMT drug manufactured using standardized processes and available in a ready-to-use format.
Patients with at least 2 recurrent CDI episodes or at least 2 severe episodes resulting in hospitalization were enrolled in a prospective, multicenter open-label study of RBX2660 administered via enema. Intensive surveillance for adverse events (AEs) was conducted daily for 7 days following treatment and then at 30 days, 60 days, 3 months, and 6 months. The primary objective was product-related AEs. A secondary objective was CDI-associated diarrhea resolution at 8 weeks.
Of the 40 patients enrolled at 11 centers in the United States between 15 August 2013 and 16 December 2013, 34 re-ceived at least 1 dose of RBX2660 and 31 completed 6-month follow-up. Overall efﬁcacy was 87.1% (16 with 1 dose and 11 with 2 doses). Of 188 reported AEs, diarrhea, ﬂatulence, abdominal pain/cramping, and constipation were most common. The frequency and severity of AEs decreased over time. Twenty serious AEs were reported in 7 patients; none were related to RBX2660 or its administration.
Among patients with recurrent or severe CDI, administration of RBX2660 via enema appears to be safe and effective.
Clinical Trials Registration: NCT01925417.
Keywords: fecal microbiota transplant; Clostridium difficile; microbiome; safety.