(838) A 13-Year Longitudinal Clinicomolecular Analysis of Determinants of ICU Admission in GBS Infections

Introduction: Group B Streptococcus (GBS) is a leading cause of late-onset sepsis in infants in the US and a substantial contributor to overall ICU admissions. The pathogenic determinants of severe disease and correlates of immunity are yet to be established

Methods: We included all children admitted to Boston Children’s Hospital with GBS isolated from a sterile site over a 13-year period (2008-21). Serotyping, multilocus serotyping and clonal complex (CC) classification were performed on each sequenced isolate for molecular characterization. A phylogenetic tree was created to contextualize these isolates using SNP distances in the core and accessory genome. The pathogen genomic determinants (surface proteins, virulence factors and AMR determinants) were then correlated with clinical, laboratory and demographic data from each patient using a combination of statistical and machine-learning methods

Results: During the study period, GBS isolates and patient data from 87 patients were analysed after obtaining IRB approval. Overall, 40% of patients required ICU care and 26% had evidence of meningitis. Serotype III (N=48, 55.2% of all isolates) and CC17(N=37, 47.4%) were the most predominant serotype and clonal complex, respectively. The distribution of serotypes was stable across the study period. A similar heterogeneity in serotype, clonal complex, surface proteins, virulence factors and antimicrobial resistance was observed when contextualised with data from 600 strains from the US CDC and 1200 other globally representative strains. Using a combination of logistic regression, decision trees and random forests, pilus proteins PI1, PI2A, PI2B and surface proteins SRR1 and SRR2 were the antigens most significantly associated with requirement for ICU admission and presence of meningeal infection. Anemia, leucocytosis/leucopenia, neutropenia, CRP and dyselectrolytemia were not significant predictors of severe disease

Conclusions: The GBS molecular population in this study was compositionally comparable to globally representative strains with serotype III as the dominant strain. Infants with this infection have high rates of ICU admissions. The pilus and surface proteins were significantly associated with severe clinical manifestations and thus may be potential targets for therapeutic and immunological interventions