Evolutionary dynamics of vancomycin-resistant Enterococcus faecium during gastrointestinal tract colonization and bloodstream infection in immunocompromised pediatric patients

Patients with hematological malignancies or undergoing hematopoietic stem cell transplantation are particularly vulnerable to becoming colonized and infected with multidrug-resistant organisms, including vancomycin-resistant Enterococcus faecium (VREfm). Over a ten-year period, we collected and sequenced the genomes of 110 VREfm isolates from stool and blood cultures of 24 pediatric patients undergoing chemotherapy or hematopoietic stem cell transplantation for hematological malignancy at St. Jude Children's Research Hospital. We used patient-specific reference genomes to identify variants that arose over time in subsequent stool and bloodstream isolates from each patient, and analyzed these variants to understand how VREfm adapted during colonization and bloodstream infection within each patient.