Clinical and genomic features of mitis group streptococcal bacteremia in patients with febrile neutropenia.
BACKGROUND: Viridans group streptococci (VGS) can cause the life-threatening viridans streptococcal shock syndrome (VSSS) in patients with febrile neutropenia (FN). The Mitis group, a major subgroup of VGS, is frequently implicated in these severe infections, but its specific clinical and genomic characteristics remain incompletely characterized, particularly in patients with FN. This study aimed to systematically describe these features in this population. METHODS: In this single-center retrospective study, we compared the clinical data and whole-genome sequencing (WGS) results of Mitis group streptococcal isolates from patients with and without FN. Virulence-associated and antimicrobial resistance genes were initially screened using a reference-based approach, followed by assembly-based reanalysis and manual sequence validation. RESULTS: Compared with the non-FN cohort (n = 34), the FN cohort (n = 61) was significantly younger, had a higher prevalence of hematologic malignancy, and more frequently presented with primary bacteremia. VSSS occurred exclusively in the FN group (11.5%) and was associated with high mortality (14-day mortality, 42.9%), which did not correlate with in vitro antimicrobial susceptibility. Genomic analyses revealed marked diversity among isolates. Initial screening suggested variable detection of several virulence-associated loci, including pavA, slrA, and rfb-related loci; however, subsequent assembly-based analyses indicated that many apparent absences were attributable to extreme allelic divergence rather than true gene loss. No single virulence determinant clearly segregated with clinical severity. CONCLUSIONS: Mitis group bacteremia in patients with FN appears to be characterized by distinct clinical features and marked genomic diversity. Our findings suggest that the development of severe disease, including VSSS, may not be explained by microbial factors alone and potentially reflects complex host-pathogen interactions. CLINICAL TRIAL: Not applicable.