Oral Capsulized Fecal Microbiota Transplantation for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization With a Metagenomic Perspective

Abstract

Background Carbapenemase-producing Enterobacteriaceae (CPE) infections lead to considerable morbidity and mortality. We assessed the potential of fecal microbiota transplantation (FMT) to eradicate CPE carriage and aimed to explain failure or success through microbiome analyses. Methods In this prospective cohort study, all consenting eligible CPE carriers were treated with oral capsulized FMT for 2 days. The primary outcome was CPE eradication at 1 month, defined by 3 consecutive negative rectal swabs, the last also negative for carbapenemase gene by PCR. Comprehensive metagenomics analysis of the intestinal microbiome of donors and recipients before and after FMT was performed. Results Fifteen CPE carriers received FMT, 13 of which completed 2 days of treatment. CPE eradication at 1 month was successful in 9/15 and 9/13, respectively. Bacterial communities showed significant changes in both beta and alpha diversity metrics among participants achieving CPE eradication that were not observed among failures. Post-FMT samples' beta-diversity clustered according to the treatment outcome, both in taxonomy and in function. We observed a significant decrease in beta diversity in participants who received post-FMT antibiotics. Enterobacteriaceae abundance decreased in post-FMT samples of the responders, but increased among failures. Functionally, a clear demarcation between responders (who were similar to the donors) and failures was shown, driven by antimicrobial resistance genes. Conclusion Our study provides the biological explanation for the effect of FMT against CPE carriage. Decolonization of CPE by FMT is likely mediated by compositional and functional shifts in the microbiome. Thus, FMT might be an efficient strategy for sustained CPE eradication.

Is there a role of faecal microbiota transplantation in reducing antibiotic resistance burden in gut? A systematic review and Meta-analysis

“…This observation was in contrast to that in case-series studies, where PPIs (omeprazole and pentaprazole) were used in all studies as a pre-treatment in different time points, except in Leo et al. [ 49 ] Bowel cleansing was not conducted in any of the case studies/reports, but it has been applied in many case series studies [ 55–57 ]. Except in one case study [ 64 ], the FMTs in all included studies were procured from unrelated healthy donors.…”

“…Out of fourteen studies, the majority are case reports or case studies ( n = 7) followed by different types of case series ( n = 5) and two ( n = 2) in vivo studies involving mice models. Out of the five case series studies, two ( n = 2) were carried out in multiple centres (Switzerland, Netherland, France, and Israel) [ 49 , 50 ], while the remaining ( n = 3) are single-center studies [ 55–57 ]. Most of the case reports/studies ( n = 5/7) were carried out in Europe; namely, Denmark ( n = 2) [ 58 , 59 ], Poland ( n = 2) [ 60 , 61 ], Netherland ( n = 1) [ 62 ], and one study each in USA [ 63 ] and South Africa [ 64 ].…”

“…Among most case studies/reports ( n = 5/7), fresh stool samples were used and diluted with sodium chloride solutions (saline). In contrast, FMT was applied as capsules from frozen stool samples ( n = 3/5) with a dosage of 15 capsules/day for two consecutive days, in case series studies [ 49 , 50 , 55 ]. Among capsule-based FMTs, one study used 80% of glycerol instead of 10% in preparation of the capsule, to increase the stability [ 50 ].…”

Next Generation Fecal Microbiota Transplantation

“…An RCT reported that FMT using the capsules was not inferior to that using colonoscopic infusion in patients with recurrent CDI (capsule, 96.2% [51/53] vs colonoscopic infusion, 96.2% [50/52]; risk difference, 0%) [ 12 ]. Further, the capsule- mediated FMT was used for eradication of Carbapenemase-producing Enterobacteriaceae (CPE) colonization [ 13 ]. A total of 30 oral capsules, containing 25 to 30 g stool in total, were ingested during two consecutive days.…”

“…Changes in specific microbial taxa have been suggested as important factors for the efficacy of FMT, especially for non-CDI diseases. For instance, Bifidobacterium bifidum abundance has been reported to increase after FMT for CPE [ 13 ]. However, the bacterial composition after FMT differed between those who showed remission (FMT responders) and lack of remission (non-responders) in UC patients [ 29 ].…”