Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study

Abstract

Background Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI. Methods An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N = 16) or two doses of RBX2660 (N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms. Results Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted. Conclusions Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others. Trial registration ClinicalTrials.gov, NCT01925417; registered on August 19, 2013.

Tandem fecal microbiota transplantation cycles in an allogeneic hematopoietic stem cell transplant recipient targeting carbapenem-resistant Enterobacteriaceae colonization: a case report and literature review

“…These reports supported not only FMT efficacy but also demonstrated that FMT in allo-HSCT settings was safe and tolerable. Furthermore, some studies have also suggested a significant reduction in antibiotic-resistant gene carriage in recipient microbiota following FMT for CDI [55][56][57].…”

Oxidative Stress and Gut Microbiome in Inflammatory Skin Diseases

“…Current strategies for regulating gut microbes include dietary interventions, prebiotic, bacteriophages, small molecules, drugs, fecal bacteria transplantation (FMT), and live biological agents (LBPs), et al ( Mahdavinia et al, 2019 ; Sorbara and Pamer, 2022 ). Many microbiome-based clinical trials are underway, such as the phase three clinical trial of fecal microbiota transplantation of Clostridioides difficile infection ( Langdon et al, 2021 ).…”

Application of Microbiome Management in Therapy for Clostridioides difficile Infections: From Fecal Microbiota Transplantation to Probiotics to Microbiota-Preserving Antimicrobial Agents

“…Some commercialized products have been developed for FMT [ 34 ]. To utilize FMT with a high abundance of non-resistant species to displace antibiotic-resistant organisms from the recipient’s microbiome, RBX2660, a liquid suspension of donor microbiota, has recently been deployed to treat rCDIs [ 34 ].…”

“…Some commercialized products have been developed for FMT [ 34 ]. To utilize FMT with a high abundance of non-resistant species to displace antibiotic-resistant organisms from the recipient’s microbiome, RBX2660, a liquid suspension of donor microbiota, has recently been deployed to treat rCDIs [ 34 ]. RBX2660 was found to aid in the successful prevention of rCDIs, correlated with the taxonomic convergence of patient microbiota to the donor microbiota, and also dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae [ 34 ].…”