Improvement of Microbiome Health Index in Patients with Recurrent Clostridiodes difficile Infections Following RBX2660 Treatment is Associated with a Reduction in Antimicrobial Resistance Genes

Courtney Jones BS, Ken Blount PhD, Tonya Ward PhD, Elena Deych MS, Bill Shannon PhD, MBA

Improvement of Microbiome Health Index in Patients with Recurrent Clostridiodes difficile Infections Following RBX2660 Treatment is Associated with a Reduction in Antimicrobial Resistance Genes

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ASM Microbe 2019
June 20-24, 2019, San Francisco, CA

Background

  • RBX2660, a standardized, stabilized microbiota restoration drug has been shown to prevent recurrent Clostridiodies difficile infections (rCDI).
  • A preliminary analysis demonstrated decolonization of multidrug-resistant organisms (MDRO) in association with clinical response.
  • In parallel, we are developing a Microbiome Health Index (MHI™) to monitor dysbiosis and microbiome restoration.
  • Given the public health challenges related with MDROs, we evaluated MHI as a potential sentinel of MDRO colonization among rCDI patients who responded to RBX2660 in a Phase 2 clinical trial.

Methods

  • The PUNCH CD2 Phase 2 trial (NCT02299570) compared RBX2660, a microbiota-based investigational drug for treatment of rCDI, to placebo.
  • 127 participants were enrolled, randomized, and treated in three cohorts: Group A: two doses of RBX2660; Group B, two placebo doses; Group C, one dose of RBX2660 and one dose of placebo.
  • Samples were collected prior to treatment (BL) and 7, 30 & 60 days after treatment.
  • This analysis is based on samples from 55 patients who responded to RBX2660 treatment in Groups A and B (pooled) and dosed RBX2660 product samples.
  • Stool samples were sequenced using BoosterShot (CoreBiome, Minneapolis, MN), an ultra-shallow shotgun sequencing method.
  • Microbiome Health Index (MHI) values were calculated based on relative abundances at the class level for selected classes.
  • Prior receiver operator characteristic analyses defined an MHI cut-point of 8.2 for distinguishing rCDI subjects prior to treatment from the representative microbiome composition of RBX2660.
  • Relative abundance of antimicrobial resistance (AMR) genes and enzymes were determined for all samples based on a threshold of ≥ 90% coverage when compared to the MEGARes database .

RBX2660 Efficacy in a Phase 2 Controlled Trial

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Microbiome Composition Shifts Post-RBX2660

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Microbiome Health Index (MHI) Analysis

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Relationship Between MHI and Antimicrobial Resistance Genes

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Conclusions

  • MHI can effectively distinguish patients with dysbiosis from healthier patients, as defined by the RBX2660 product profile and the Human Microbiome Project.
  • MHI inversely correlates with AMR gene abundance in a cohort of rCDI patients who had successful response to RBX2660.
  • These results suggest MHI as a potential sentinel of MDRO colonization, and this role will be evaluated in future cohorts outside of the rCDI patient population.