* BAZ = body mass index-for-age Z-score; BMI = body mass index; DF = dengue fever; DHF = dengue hemorrhagic fever; HAZ = height-for-age Z-score; HC = healthy controls; IQR = interquartile range; WAZ = weight-for-age Z-score.† Assessed only in children under 120 months of age, DHF n = 44, DF n = 52, HC = 71.

Patients with hematological malignancies or undergoing hematopoietic stem cell transplantation are vulnerable to colonization and infection with multidrug-resistant organisms, including vancomycin-resistantEnterococcus faecium(VREfm). Over a 10-y period, we collected and sequenced the genomes of 110 VREfm isolates from gastrointestinal 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 gastrointestinal and blood isolates from each patient and analyzed these variants for insight into how VREfm adapted during colonization and bloodstream infection within each patient. Variants were enriched in genes involved in carbohydrate metabolism, and phenotypic analysis identified associated differences in carbohydrate utilization among isolates. In particular, a Y585C mutation in the sorbitol operon transcriptional regulatorgutRwas associated with increased bacterial growth in the presence of sorbitol. We also found differences in biofilm-formation capability between isolates and observed that increased biofilm formation correlated with mutations in the putativeE. faeciumcapsular polysaccharide (cps) biosynthetic locus, with different mutations arising independently in distinct genetic backgrounds. Isolates withcpsmutations showed improved survival following exposure to lysozyme, suggesting a possible reason for the selection of capsule-lacking bacteria. Finally, we observed mutations conferring increased tolerance of linezolid and daptomycin in patients who were treated with these antibiotics. Overall, this study documents known and previously undescribed ways that VREfm evolve during intestinal colonization and subsequent bloodstream infection in immunocompromised pediatric patients.

A virtual consensus conference proposal on advanced diagnostics for transplant infectious diseases was submitted by the AST Transplant Diagnostics Community of Practice (TxDxCOP) for consideration and subsequently approved for funding. The consensus conference was fully virtual; participants received no funds from private enterprises. AST provided organizational and technical support for pre-conference and conference proceedings. A steering committee comprising members of TxDxCOP and the Infectious Diseases Community of Practice developed conference definitions, aims, scope, and format. Advanced or novel assays were defined as assays with the capacity for one or more of the following: To detect (1) pathogens, (2) genotypic or phenotypic antimicrobial susceptibility, or (3) pathogen-specific host responses, with an enhanced range of target detection, sensitivity, specificity, speed and/or simplicity of use, relative to conventional methods. Assay categories that met the above definition and for which some data on clinical performance/utility was available were included in this consensus conference.

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