419. Changing Epidemiology of Pediatric Invasive Group A <i>Streptococcus</i> Infections in the United States, 2004-2022

Abstract Background Recent reports from children’s hospitals of increasing pediatric invasive Group A Streptococcus (iGAS) infections triggered national concern. Clindamycin and penicillin dual therapy is often recommended for iGAS, which is life-threatening. We used active, population and laboratory-based surveillance to assess changes in pediatric iGAS disease incidence, clinical outcomes, and bacterial strain characteristics between 2004–2022. Methods Using CDC’s Active Bacterial Core surveillance network, we identified pediatric iGAS cases (GAS isolation from a normally sterile site in persons aged ≤17 years) from 2004–2022. CDC Streptococcus laboratory characterized available isolates by emm typing and antimicrobial susceptibility using conventional and genomic methods. We compared annual incidence during 2004–2019 (pre-COVID-19 pandemic), 2021 (mid COVID-19 pandemic), and 2022 (relaxation of pandemic mitigation measures). Case fatality ratio (CFR), intensive care unit (ICU) admission, and clindamycin non-susceptibility trends (2011-2022) were assessed with the Cochran-Armitage test. Results We identified 2,522 pediatric iGAS cases during 2004–2022. Incidence decreased from 1.9 cases per 100,000 persons (2004–2019) to 0.5 (2021) (Incidence Rate Ratio: 0.29 [95% CI: 0.25-0.32]; P&amp;lt; .001) but increased in 2022 to 1.5 (2021 vs 2022 IRR: 2.9 [95% CI: 2.6-3.2]; P&amp;lt; .001). Thirty-four percent of cases were admitted to the ICU; admission increased from 28.9% (2011) to 36.1% (2022) (P = .04). CFR (3.1%) remained stable (P = .69). All isolates were penicillin susceptible; clindamycin non-susceptibility increased from 3.8% (2011) to 28.1% (2021), before declining to 8.4% (2022) (2011 vs 2022 P = .01). emm1, which accounted for 44.8% of ICU admissions (2011-2022) and 38.5% of fatal cases, decreased to 3.1% of isolates in 2021. Conclusion Pediatric iGAS incidence was stable for 15 years before declining substantially in 2021. Infections due to emm1, the most identified emm type in children with severe disease, almost disappeared in 2021, potentially due to initiation of COVID-19 mitigation measures; however, clindamycin non-susceptibility continued to increase. Rising iGAS incidence in 2022 necessitates close monitoring for rises in emm1 infections and antimicrobial resistance. Disclosures Lee Harrison, MD, GSK: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant