Clearance of Vancomycin-Resistant Enterococcus Concomitant With Administration of a Microbiota-based Drug Targeted at Recurrent Clostridium difficile Infection

Erik R. Dubberke,¹ Kathleen M. Mullane,² Dale N. Gerding,^3,4 Christine H. Lee,⁵ Thomas J. Louie,⁶ Harriet Guthertz,⁷ and Courtney Jones⁸

¹Department of Medicine,Washington University School of Medicine, St. Louis, Missouri; ²Section of Infectious Diseases and Global Health, University of Chicago Medicine, ³Department of Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, and ⁴Edward Hines Jr. Veterans Affairs Hospital, Hines, Illinois; ⁵Department of Medicine, McMaster University, Hamilton, Ontario, and ⁶Departments of Medicine and Microbiology-Immunology and Infectious Diseases, University of Calgary, Alberta, Canada; ⁷Medical Marketing and Communications, Inc., St. Paul, Minnesota; and ⁸Rebiotix Inc., Roseville, Minnesota

Background

Vancomycin-resistant Enterococcus (VRE) is a major healthcare-associated pathogen and a well known complication among transplant and immunocompromised patients. We report on stool VRE clearance in a post hoc analysis of the Phase 2 PUNCH CD study assessing a microbiota-based drug for recurrent Clostridium difficile infection (CDI).

Methods

A total of 34 patients enrolled in the PUNCH CD study received 1 or 2 doses of RBX2660 (microbiota suspension). Patients were requested to voluntarily submit stool samples at baseline and at 7, 30, and 60 days and 6 months after the last administration of RBX2660. Stool samples were tested for VRE using bile esculin azide agar with 6 µg/mL vancomycin and Gram staining. Vancomycin resistance was confirmed by Etest.

Results

VRE status (at least 1 test result) was available for 30 patients. All stool samples for 19 patients (63.3%, mean age 61.7 years, 68% female) tested VRE negative. Eleven patients (36.7%, mean age 75.5 years, 64% female) were VRE positive at the first test (baseline or 7-day follow-up). Of these patients, 72.7%, n = 8 converted to negative as of the last available follow-up (30 or 60 days or 6 months). Of the other 3: 1 died (follow-up data not available); 1 patient remained positive at all follow-ups; 1 patient retested positive at 6 months with negative tests during the interim.

Conclusions

Although based on a small sample size, this secondary analysis demonstrated the possibility of successfully converting a high percentage of VRE-positive patients to negative in a recurrent CDI population with RBX2660.

Clinical Trials Registration: NCT01925417.
Keywords: Clostridium difficile, microbiota-based drug, RBX2660, vancomycin-resistant, Enterococcus, VRE.