We retrospectively collected the clinical and microbiological data from patients with positive cultures of GAS from the medical and microbiological records at seven hospitals across three municipalities in Okayama Prefecture, Japan (Okayama University Hospital, NHO Okayama Medical Center, Okayama Saiseikai General Hospital, Okayama City Hospital, Tsuyama Chuo Hospital, Okayama Kyoritsu Hospital, Takahashi Central Hospital), between January 1, 2022, and June 30, 2024. Five institutions (Okayama University Hospital, NHO Okayama Medical Center, Okayama Saiseikai General Hospital, Okayama City Hospital, Okayama Kyoritsu Hospital) were located in Okayama City (population approximately 700,000). Tsuyama Chuo Hospital and Takahashi Central Hospital cover Tsuyama City (population approximately 100,000) and Takahashi City (population approximately 29,000), respectively, based on 2020 census data. Among participating institutions, Okayama University Hospital and Tsuyama Chuo Hospital were designated tertiary care hospitals, while the others were secondary acute care hospitals. Ethical approval was obtained from the Institutional Review Board of Okayama University Hospital (No. 2406-015). The requirement for informed consent was waived due to the retrospective nature of the study, which involved the use of fully anonymized, routinely collected data.

We included cases of patients with positive cultures of GAS from any specimen during the study period. Episodes with intervals of three months or more were defined as different cases.

The patients diagnosed with GAS were classified as either infectious or carrier cases. STSS is a notifiable disease classified as a category V infectious disease that must be reported upon diagnosis [18]. Thus, when patients with this condition, medical practitioners are obligated to inform local public health centers using reporting documents. Since April 2006, all cases of the locally-defined STSS caused by β-hemolytic streptococci are supposed to be reported as category V infectious diseases.

We retrospectively collected the following information from patient medical records: age, sex, time of diagnosis, underlying conditions, specimen type from which GAS was detected, clinical diagnosis, notification status as a category V infectious disease, surgical procedures performed, admission to the ICU, and in-hospital mortality. Age groups were categorized in 10-year increments. To analyze the temporal trend of GAS infections, we divided the study period into six-month intervals: January–June in 2022, July–December in 2022, January–June in 2023, July–December in 2023, and January–June in 2024.

A patient was defined as a GAS carrier if the bacteria were detected at a body site other than the focus of infection or if the attending physician determined that the patient was a carrier. We categorized the infectious foci into six groups: pharyngitis, lower respiratory infections, skin and soft tissue infections (SSTIs), abdominal and pelvic infections, genital infections, and other infections. The infectious foci were determined in most cases by the attending physician based on a match between the site of infection and the site of an obtained specimen. The pharyngitis category encompasses peritonsillar abscess cases confirmed through microbiological cultures from pharyngeal specimens or purulent material obtained from peritonsillar collections. The iGAS infections were defined according to the United States Centers for Disease Control and Prevention (CDC)’s Active Bacterial Core surveillance criteria, comprising cases of STSS, necrotizing fasciitis, and isolation of GAS from normally sterile anatomical sites, including but not limited to blood, cerebrospinal fluid, synovial fluid, peritoneal fluid, osseous tissue, and internal organs [4, 5].We investigated several comorbidities, including hypertension, cardiovascular disease, diabetes mellitus, malignancy, skin disorder, chronic obstructive pulmonary disease or asthma, kidney disorder, liver disorder, mental disorder, and others. Whole-genome sequence analysis of GAS strains isolated from notified cases commenced in January 2024 in Japan, prompted by the increased incidence of GAS infections and the potential emergence of the M1UK in 2023. We also gathered this data from the participating hospital.

The primary outcomes assessed included the difference of ICU admission, the need for surgical intervention, notification as a Category V infectious disease, and in-hospital mortality between patients with notified STSS cases and unreported cases. The secondary outcome focused on the difference between SSTI and other cases. Continuous variables were presented as medians with interquartile ranges (IQRs) and evaluated using the Kruskal–Wallis test or Mann–Whitney U test. Categorical variables were reported as numbers and percentages and were assessed using the Chi-square or the Fisher’s exact test. Data analysis was conducted using EZR software, a graphic user interface for the R 3.5.2 software (The R Foundation for Statistical Computing, Vienna, Austria). All reported p values < 0.05 were considered statistically significant.