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Background   Streptococcus pyogenes  is a major cause of severe, invasive infections in humans. The bacterial pathogen harbors a wide array of virulence factors and exhibits high genomic diversity. Rapid changes of circulating strains in a community are common. Understanding the current prevalence and dynamics of  S. pyogenes  lineages could inform vaccine development and disease control strategies.    Methods  We used whole-genome sequencing (WGS) to characterize all invasive  S. pyogenes  isolates obtained through the United States Center for Disease Control and Prevention’s Active Bacterial Core surveillance (ABCs) in 2016 and 2017. We determined the distribution of strain features, including  emm  type, antibiotic resistance determinants, and selected virulence factors. Changes in strain feature distribution between years 2016 and 2017 were evaluated. Phylogenetic analysis was used to identify expanding lineages within  emm  type.    Results  Seventy-one  emm  types were identified from 3873 isolates characterized. The  emm  types targeted by a 30-valent M protein-based vaccine accounted for 3230 (89%) isolates. The relative frequencies of  emm  types collected during the 2 years were similar. While all isolates were penicillin-susceptible, erythromycin-resistant isolates increased from 273 (16% of 2016 isolates) to 432 (23% of 2017 isolates), mainly driven by increase of the  erm -positive  emm  types 92 and 83. The prevalence of 24 virulence factors, including 11 streptococcal pyrogenic toxins, ranged from 6 to 90%. In each of three  emm  types ( emm  49, 82, and 92), a subgroup of isolates significantly expanded between 2016 and 2017 compared to isolates outside of the subgroup ( P -values < 0.0001). Specific genomic sequence changes were associated with these expanded lineages.    Conclusions  While the overall population structure of invasive  S. pyogenes  isolates in the United States remained stable, some lineages, including several that were antibiotic-resistant, increased between 2016 and 2017. Continued genomic surveillance can help monitor and characterize bacterial features associated with emerging strains from invasive infections.

Genomic Surveillance of Streptococcus pyogenes Strains Causing Invasive Disease, United States, 2016–2017