Gut translocation of antimicrobial resistant pathogens in patients undergoing haematopoietic stem cell transplantation in India

Abstract Background Patients undergoing haematopoietic stem cell transplantation (HSCT) in low- and middle-income countries face high rates of antimicrobial resistant (AMR) bloodstream infections (BSIs), but the origins and dynamics of these infections remain poorly understood. Results We prospectively studied 81 HSCT patients in India, collecting 252 longitudinal stool samples and applying an enrichment-based metagenomic approach to selectively recover priority AMR pathogens. This strategy enabled high-resolution metagenome-assembled genomes and strain tracking. We identified a marked depletion of gut resistomes during pre-engraftment, followed by a rapid rebound with engraftment, driven by expansion of plasmid-borne carbapenemase and ESBL genes (blaNDM, blaOXA). Using whole genome sequencing, Hi-C metagenomics, and strain-level comparisons (> 99.9% ANI), we directly linked gut-colonising organisms to five culture-confirmed AMR-BSI episodes, providing genomic evidence of gut translocation. Patients with BSIs had high mortality (> 40%), underlining the clinical impact of these events. Conclusions We demonstrate that stool-based enrichment metagenomics is a practical and cost-effective approach for non-invasive monitoring of gut recovery and AMR risk after HSCT. Our findings provide the first direct genomic evidence of gut-derived AMR-BSIs in an LMIC cohort, highlighting translocation as a major driver of post-transplant mortality and a critical target for surveillance and intervention.