Fecal microbiota transplantation accelerates clearance of carbapenemase-producing Enterobacterales intestinal carriage: influence of recipient gut microbiome ecology.

BACKGROUND: Persistent intestinal carbapenemase-producing Enterobacterales (CPE) carriage challenges infection prevention and antimicrobial stewardship. We evaluated fecal microbiota transplantation (FMT) for decolonization and response-associated recipient microbiome features. METHODS: This prospective cohort study assessed intestinal CPE clearance in 131 adult carriers (68 receiving FMT; 63 under observation). Responders achieved clearance, defined as three consecutive negative rectal surveillance cultures for CPE, obtained at 3-day intervals within 1 month after FMT. Following least absolute shrinkage and selection operator (LASSO)-based covariate selection, Cox proportional hazards models estimated associations between FMT and time to successful decolonization within prespecified 0-30-day and 0-90-day windows. A longitudinal metagenomic subcohort of 21 FMT recipients (102 fecal samples) underwent shotgun sequencing to characterize taxonomic composition, microbial network organization, functional pathways, antimicrobial resistance genes (ARGs), and donor engraftment. RESULTS: After LASSO-based covariate selection, FMT was associated with faster CPE clearance than observation at 1 month (hazard ratio, 4.02; 95% confidence interval, 1.84-8.79), with effects sustained at 3 months. Responders showed relatively preserved baseline microbial network organization and enrichment of taxa annotated with arginine-related pathway features, suggesting metabolic relevance to microbial niche competition. After FMT, responders had greater engraftment of donor-associated taxa and donor-like ecological reassembly, with reduced Klebsiella pneumoniae dominance and ARG abundance. CONCLUSIONS: FMT may accelerate intestinal decolonization in CPE carriers; response variability was associated with recipient gut-microbiome ecology, suggesting microbiome-guided patient selection could optimize microbiota-based strategies.