From 2022 onwards, several countries, including the Netherlands, reported a marked increase in invasive group A streptococcal (iGAS) infections. Therefore, we aimed to describe the clinical presentation, disease course, treatment and outcomes of group A streptococcus (GAS) meningitis, a rare but severe manifestation of GAS infection in pediatric patients. Children with GAS meningitis were selected from the COPP-iGAS study, a national observational cohort study in children 0-17 years of age with in-hospital diagnosis of iGAS between 2015 and June 2024, conducted across 20 hospitals in the Netherlands, including all 7 academic centers with a pediatric intensive care unit. Twenty-seven children were included, of whom 41% (11/27) were younger than 5 years of age. Most patients presented during the first quarter of the year (n = 13/27, 48%). Admission to an intensive care unit occurred in 15/27 (56%) patients and 4/27 (15%) patients died. Detailed clinical data were available for 13/27 patients. Clinical course data could be evaluated for 12 of these patients. Among those 12 patients, almost two-thirds had a complicated disease course, mainly involving cardiorespiratory failure (4/12, 33%). All 12 patients received prolonged antibiotic therapy [median 43 days (IQR 14-61)], predominantly intravenously [median 42 days (IQR 14-50)]. Adjunctive therapy included corticosteroids (6/12, 50%), antiviral agents (3/12, 25%) and anticoagulants (3/12, 25%). Our findings highlight that pediatric GAS meningitis is a severe condition characterized by high intensive care admission rates and substantial mortality. In the subgroup with detailed clinical data, complications were frequent and prolonged antibiotic treatment was common. Increased clinical awareness is warranted.

Pediatric invasive Group A Streptococcus (iGAS) infections are rare, affecting sterile sites including the central nervous system (CNS), and cause significant morbidity and mortality. An increased incidence of pediatric iGAS infections, including cases with CNS involvement, has been noted following the COVID-19 pandemic both domestically and internationally. Regional New England iGAS data specific to pediatric populations have been limited. This case series describes three pediatric cases of iGAS with CNS involvement which presented within the same two-month period in early 2025, all from within 20 miles in Massachusetts. All were initially admitted to the pediatric intensive care unit, patients had meningitis and subdural collections on brain imaging, and subsequently required at least four weeks of intravenous antibiotics. One underwent surgical intervention. All three had seizures requiring long-term anti-epileptic therapy, and each had residual symptoms, including seizures, focal weakness, and developmental delay. GAS infections with intracranial involvement are often severe and life-threatening. This series of three pediatric intracranial iGAS cases is particularly unique due to their similar presentations, timing, and geographic proximity. With recent literature indicating rising rates of iGAS infections globally and our regional experience, GAS should be considered a potential culprit for patients presenting with invasive bacterial infections.

To describe the epidemiological and clinical characteristics of children with invasive group A Streptococcus (iGAS) infection and severe GAS-associated lower respiratory tract infections (including empyema) [LRTIs] identified in England in late 2022, supporting earlier recognition and informing pre-hospital admission clinical decision and public health response. Case series analysis. LRTI iGAS cases in children aged <15y in England reported between October 01 and December 21, 2022, were identified using laboratory data (GAS detected in LRT specimens) and notifications by clinicians. Symptoms, diagnoses, healthcare interactions, and outcomes were described based on case management notes, the National Child Mortality Database, and the national Emergency Care Dataset (ECDS). Across England, 147 paediatric cases of LRTI iGAS were reported, 52% male and with a median age of four (IQR 2-6) years. Most reported symptoms were fever (75%; n=90) and cough (50%; n=60). Half (50%, n=74) had a confirmed respiratory viral coinfection. Over three-quarters (77%, n=113) attended an emergency department and 25% died (n=37/147), with a median of four days from symptom onset to death. Over half of these deaths (n=21/37) occurred in the community, with several (n=6) cases having rapid deterioration recorded. Of cases who died, 81% (n=21/26) had their GAS-positive sample taken shortly before death or post-mortem. Viral-like symptoms, and the presence or suspicion of viral co-infection, combined with rapid deterioration made prompt identification of iGAS infection challenging, despite high healthcare engagement. Early recognition and timely treatment remain critical to reducing morbidity and mortality in these cases.

To the Editors: Group A streptococcus (GAS), also known as Streptococcus pyogenes, is an anaerobic, gram-positive beta-hemolytic bacterium that commonly colonizes the nasopharynx and skin.1 M proteins facilitate adhesion to the mucosal membrane, particularly the tonsils, facilitating epithelial invasion. GAS produces toxins, resulting in tissue damage and deeper infections due to immune complex formation.1 Clinical manifestations range from localized infections of the ear, nose, throat and lungs to disseminated infections, cytokine-induced shock, immune complex-mediated diseases and diseases associated with molecular mimicry. We present a case of a 3-year-old girl with a severely complicated invasive GAS (iGAS) infection, highlighting the importance of early recognition, prompt initiation of appropriate treatment and awareness of potential severe complications. A previously healthy 3-year-old girl presented with a 5-day history of high fever, ear pain, poor oral intake, oliguria and vomiting. One day before admission, she was diagnosed with bilateral acute otitis media and treated with oral amoxicillin. On examination, she appeared ill with tachypnea (36 per minute), tachycardia (163 per minute), high blood pressure (103/70 mm Hg), cold extremities and delayed capillary refill, with normal oxygen saturation. Breath sounds were reduced on the right. Laboratory tests showed elevated C-reactive protein (429 mg/L), leukocytosis (18.3 × 109/L) and mild thrombocytopenia (113 × 109/L). Chest radiograph revealed bronchial wall thickening and left-sided multifocal consolidations suspicious for pneumonia, and intravenous amoxicillin–clavulanic acid was initiated. One day after admission, an adenovirus was detected in the nasopharynx, and blood cultures grew GAS. She rapidly developed sepsis, requiring fluid resuscitation and the addition of clindamycin for suspected toxic shock. The following days, her condition deteriorated with edema, strawberry tongue, coagulopathy and the need for oxygen therapy. Also, the patient developed an isolated horizontal and vertical nystagmus, which raised suspicion for intracranial spread, whereafter amoxicillin–clavulanic acid was switched to ceftriaxone. Magnetic resonance imaging showed acute otomastoiditis, suspected labyrinthitis, and transverse and sigmoid sinus thrombosis with internal jugular vein thrombophlebitis (Fig. 1). Subsequently, she developed meningitis, culture-positive mastoiditis requiring mastoidectomy and bilateral hip arthritis. After more than 4 weeks of hospitalization, intravenous antibiotics and anticoagulation, she was discharged home for further recovery.FIGURE 1.: Axial slices T2 (A), B1000 diffusion weighted image (B) and fat saturated T1 after contrast (C). A: Mastoid and middle ear are bilaterally completely filled with fluid (arrows). Additionally, no flow void in the right dural sinus whereas left dural sinus does show normal flow void (dotted arrows). B: Restricted diffusion in the right mastoid and middle ear indicating pus and therefore otomastoiditis. In contrast, the left mastoid and middle ear show no restricted diffusion indicating uncomplicated fluid. C: Filling defect in the right dural sinus (arrow) confirming the thrombosis already suspected on the T2 image. Of note: not shown are the labyrinthitis and the extracranial thrombophlebitis.Although initial treatment with amoxicillin–clavulanic acid was appropriate for community-acquired pneumonia, the rapid septic dissemination and multiorgan involvement highlight the need for early recognition of iGAS and escalation of antimicrobial therapy. Treatment of iGAS depends on clinical presentation and includes antibiotics targeting both toxin-mediated disease and metastatic spread.2 Clindamycin inhibits protein synthesis and toxin production and, when combined early with a broad-spectrum agent such as ceftriaxone, may reduce morbidity.3 Several theories could explain the recent increased incidence of iGAS.4 Reduced immune exposure during COVID-19 lockdowns may have increased susceptibility to both viral and bacterial infections, while circulating GAS strains may have led to more pathogenic and invasive bacteria. In addition, the post-pandemic rise in viral infections may predispose to secondary invasive bacterial disease.5 This case illustrates the severe and multifaceted course of iGAS infection in a young child, involving both toxic shock and bacterial dissemination. Early recognition of disease and possible complications, as well as adequate treatment, are essential to reduce adverse outcomes.

Studies have identified significant morbidity and mortality with necrotising soft tissue infections relating to invasive group A Streptococcus (iGAS). However, no studies have analysed the reconstructive, functional and psychological outcomes of invasive group A Streptococcus infections across its clinical spectrum, including the more common non-necrotising presentations. This study was a retrospective cohort study that aimed to review as primary outcomes the management, reconstructive burden and functional outcomes of soft tissue iGAS infections at a tertiary-care U.K. Plastic Surgery unit between 2013 and 2022. The secondary outcome was to identify associations between patient factors and limb amputation and mortality. All positive iGAS cultures isolated in patients aged 16 and over were identified. Medical records, operative records, and microbiology samples were examined. 96 cases of iGAS were identified in 95 patients over the study period. 63 patients (66%) were male; 34 patients (36%) were current smokers; and 35 patients (37%) were immunocompromised, including 18 patients (19%) with diabetes. 88 cases (92%) affected the upper or lower limbs, with 11 cases (13% of limb iGAS) requiring amputation of the involved digit or limb. Reconstructive surgery was performed in 15 cases (16%), requiring a mean number of 3.7 ± 1.88 operations. Reconstruction methods involved acelluar dermal matrices and/or skin grafts (14 cases; 15%) and locoregional flaps (8 cases; 8.3%). At follow up, 13 cases (14%) had functional complications relating to their iGAS episode, including neuropathic pain and limited movement. Mortality was 5.2% (5 patients) within the index admission and 7.3% (7 patients) within 90 days. Diabetes was significantly associated with 90-day mortality (p = 0.023; odds ratio [OR] 7.05, 95% confidence interval [CI] 1.41–35.00) and amputation (p = 0.033; OR 4.51, 95% CI 1.19–17.19). Other systemic comorbidities were not significantly associated with mortality or amputation. Soft tissue iGAS infections principally affect the limbs and require multimodal management to mitigate the high rates of infection-related morbidity and mortality. Diabetes is significantly associated with higher amputation and mortality rates in our study population. Appropriate services should be in place to manage long-term functional disability and mental health morbidity after iGAS.

Invasive Group A Streptococcal (iGAS) infection is relatively rare in pediatric upper respiratory tract infections, but it can breach anatomical barriers to cause deep abscesses. However, iGAS-induced rapid development of intraorbital abscess in children is extremely uncommon. Due to its high occult nature, it is easily overlooked, which may lead to permanent visual loss or even death. A 6-year-old girl was admitted to the hospital with “rhinorrhea and cough for 1 week, accompanied by fever for 2 days”. Upon admission, the pediatrician diagnosed acute tonsillitis and administered amoxicillin-clavulanate potassium for anti-infective treatment. Four hours after admission, the girl developed right eyelid edema and conjunctival congestion. Six hours after admission, obvious proptosis and diminished direct light reflex were noted in the right eye, and the pediatrician immediately initiated a multidisciplinary team (MDT) consultation. Based on the combined findings of orbital computed tomography (CT) and paranasal sinus magnetic resonance imaging (MRI), MDT confirmed the girl to have sinusitis complicated by orbital cellulitis, and that her condition had progressed to the rapidly progressive stage of intraorbital abscess. Subsequent results of blood culture and next-generation sequencing (NGS) both indicated GAS infection. After a comprehensive evaluation of all clinical indicators, the MDT formulated a treatment plan involving endoscopic sinus surgery combined with orbital abscess incision and drainage via a supraorbital eyebrow approach. The girl received 3 weeks of postoperative anti-infective therapy, with her inflammatory markers returning to normal and visual acuity restored. No recurrence was observed during the follow-up examination 6 months later. GAS could break through the lamina papyracea in a highly insidious manner, causing invasive infection of orbital tissues, followed by rapid progression of the infection. Clinical diagnosis and treatment emphasizes the rapid response of the MDT consultation. When the child presents with rapid progression of ocular symptoms, it is recommended to escalate the anti-infective regimen and perform early surgical drainage to improve prognosis. This case provides an important reference for the clinical diagnosis and treatment of severe orbital infections caused by iGAS in children.

Invasive infections caused by Streptococcus pyogenes (iGAS) have increased in Europe over the past decade, with a marked upsurge after the COVID-19 pandemic. Here, we examined whether the increase in iGAS infections in Norway was associated with the spread of variants that had acquired new virulence factors. A collection of 1,163 iGAS isolates submitted to the National Reference Laboratory between January 2017 and April 2023, representing 87% of all cases recorded by the Norwegian Surveillance System for Infectious Diseases, was analyzed by whole genome sequencing. Resistance to one or more antibiotics was found in 15.6% of the isolates: 14.1% were resistant to tetracycline, 6.4% to erythromycin, and 4.0% to clindamycin. Resistance to other antibiotics was < 1%. The dominating emm types were emm1 (30.9%), emm12 (13.8%), emm89 (9.3%), emm28 (8.3%), emm4 (6.0%), and emm87 (4.5%), with the remaining isolates belonging to 55 other emm types; 62.3% of emm1 belonged to the hypervirulent lineage M1UK. Genetic characterization of the virulence factors of the dominant six emm types demonstrated extensive competition between related phages, leading to phage switching and interplay between integration and excision of temperate phages carrying virulence factors. Bacteriophages carrying virulence factors speC and spd1 displayed a particularly high turnover rate, with several pairs of otherwise genomically identical isolates exhibiting different phage-carrying status. We identified and characterized four new speC and spd1-carrying phages. The rapid turnover pattern of these, as well as other phages carrying superantigens and DNAses suggests an important role in pathogenesis.IMPORTANCEThis analysis of 1,163 iGAS isolates collected between January 2017 and April 2023 aimed to map virulence factor content to understand the observed increased incidence of iGAS in Norway. Our findings indicate that 15.6% of the isolates were resistant to at least one antibiotic, with tetracycline resistance being the most common. The dominant emm types were emm1, emm4, emm12, emm28, emm87, and emm89, which together accounted for 72.7% of the isolates. The study highlights the dynamic nature of virulence factor-carrying temperate phages, particularly the ones carrying speC and spd1, which frequently integrate and excise within emm types. Four previously unseen phages carrying speC and spd1 were identified and characterized. This research underscores the complexity of iGAS epidemiology and the need for continuous surveillance to understand the evolving landscape of bacterial virulence factors, antibiotic resistance, and circulating emm types.

In 2024, Chile experienced an outbreak of invasive group A Streptococcus (iGAS) infections. Although increasing reports of GAS outbreaks have been described worldwide, it remains unclear whether these events are driven by increased virulence of circulating lineages or by lineage replacement. In parallel, the burden of hospitalized noninvasive GAS infections (h-niGAS), which may present with severe disease, remains poorly characterized. This study aimed to compare epidemiological, clinical, antimicrobial resistance, and genomic features of iGAS and h-niGAS infections in Chile over a six-year period. We analyzed 2,307 GAS isolates collected between 2018 and 2024, including 2,249 noninvasive isolates and 58 iGAS isolates. Noninvasive cases were classified as outpatient niGAS or hospitalized niGAS (h-niGAS). Antimicrobial susceptibility testing was performed for all isolates. emm typing was performed on isolates from hospitalized patients (28 iGAS and 94 h-niGAS). Whole-genome sequencing was performed on outbreak-related isolates, followed by virulence gene profiling and phylogenetic analysis. Clinical characteristics were compared between iGAS and non-iGAS cases and across time periods. Among niGAS isolates, 2,119 were obtained from outpatients and 130 from hospitalized patients. h-niGAS isolates showed the highest proportion of clindamycin resistance (42%), whereas iGAS isolates showed the lowest (16%). Notably, clindamycin resistance among iGAS increased from 0% during 2020-2023 to nearly 20% in 2024. The most frequent emm types were emm1, emm12, and emm4. The frequency of emm1 increased from 0% in 2020-2023 to 10% in 2024, while overall emm diversity declined markedly (Simpson's reciprocal index from 17.3 to 6.63). Clinically, iGAS infections were associated with immunosuppression, chronic liver disease, viral coinfection, and trauma. During the 2024 outbreak, iGAS cases did not differ clinically from those reported in 2018-2023; however, h-niGAS cases required more surgical procedures (p = 0.005) and medical evaluations (p = 0.025). Whole-genome sequencing revealed predominance of emm1, including three M1UK strains harboring all 27 defining single-nucleotide polymorphisms. emm1 isolates carried a higher number of virulence-associated genes compared with non-emm1 isolates (p < 0.05). Phylogenetic analysis showed close relatedness to strains from the United Kingdom, Argentina, and the United States. These findings suggest that the Chilean outbreak was driven by the expansion of the emm1 lineage rather than an increase in strain virulence. The identification of M1UK strains and the reduced emm diversity support a model of lineage introduction and clonal expansion. The significant clinical burden observed among h-niGAS cases underscores the importance of including hospitalized noninvasive infections in surveillance efforts. Ongoing integrated clinical and genomic surveillance of both iGAS and h-niGAS is essential to monitor emerging lineages and antimicrobial resistance trends.

Both invasive group A streptococcal (iGAS) infections and the number of persons experiencing homelessness (PEH) are increasing. Protection of PEH from the burden of iGAS infections requires understanding of its epidemiology. To assess whether the resurgence of iGAS infections after the COVID-19 pandemic included PEH. This cross-sectional study of population-based iGAS surveillance used Canada's National Microbiology Laboratory for emm typing and Statistics Canada and point-in-time counts to identify denominators. Participants included 503 persons with iGAS infections from January 1, 2022, to December 31, 2023, in the Toronto and Peel Region, Canada (population, 4.5 million). The main outcome was disease incidence among PEH over time and compared with housed persons. Secondary outcomes were differences in risk factors, presentation, disease severity, and infecting emm types between PEH and housed persons. Ninety iGAS cases occurred among PEH (median age, 47.0 years [IQR, 37.7-59.5 years]; 66 men [73.3%]) and 413 occurred among housed adults (median age, 58.9 years [IQR, 42.1-73.3 years]; 259 men [62.7%]). iGAS incidence among PEH increased from 270.4 (95% CI, 184.5-383.2) per 100 000 per year in 2022 to 451.2 (95% CI, 348.2-575.7) per 100 000 per year in 2023 (incidence rate ratio [IRR], 1.67; 95% CI, 1.06-2.69), not significantly different than the increase from 3.4 to 7.0 per 100 000 per year among housed persons (IRR, 2.05; 95% CI, 1.67-2.52). iGAS incidence overall was 70.7-fold higher (95% CI, 56.3-fold to 88.7-fold) among PEH than housed persons. Compared with housed adults, PEH were less likely to be immunocompromised (adjusted odds ratio [AOR], 0.29; 95% CI, 0.11-0.73) and were more likely to be persons who inject drugs (AOR, 5.06; 95% CI, 2.79-9.19), to have nonintact skin (AOR, 4.16; 95% CI, 2.45-7.04), and to have iGAS presenting as soft tissue infection (AOR, 1.64; 95% CI, 1.02-2.64). PEH were less likely to die of iGAS than housed adults (AOR, 0.33; 95% CI, 0.12-0.95). Overall, emm1 and emm12 caused 33.7% of iGAS cases (137 of 406) among housed persons, but only 2.2% (2 of 90) among PEH; in contrast, isolates with emm types 49, 74, 80, 82, and 92 caused 77.8% of iGAS cases (70 of 90) among PEH, but only 34.2% (139 of 406) among housed persons (P < .001). The emm types frequently causing iGAS infections among PEH also caused iGAS infections among housed persons and were too highly clonal to assess transmission risk. In this cross-sectional study, the post-COVID-19 pandemic resurgence of iGAS infections occurred among both PEH and housed adults, although the incidence among PEH was 70.7-fold greater. Risk factors, clinical presentations, outcomes, and infecting strains were very different. Improved iGAS protection for PEH, such as vaccines, is needed.

Invasive group A Streptococcus (iGAS) infections in children can cause severe illness and lead to high rates of complications and death. While recent global reports show a rise in pediatric iGAS after the COVID-19 pandemic, there is limited data from Saudi Arabia. Assess the clinical features, outcomes, and patterns of pediatric iGAS at a major tertiary center in Riyadh. Retrospective case series study. King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh, Saudi Arabia. Pediatric patients aged 14 years or younger who had symptoms of iGAS confirmed by a positive culture from January 2018 to May 2025. Clinical features, outcomes, and patterns of pediatric iGAS. 32 children. Out of the 585 total infections recorded, 32 cases were classified as iGAS and included in the study. Most infections happened in winter and spring, with (433/585) 74% occurring from November to April. The highest rates of iGAS were seen during the COVID-19 pandemic years. The average age of patients was 4.1 years, and 94% (n=30) had other health problems, mainly congenital heart disease (n=9, 28%) and hematology/oncology (n=8, 25%). Bacteremia was the most common presentation (n=17, 53%), followed by cellulitis/necrotizing fasciitis (n=9, 28%) and pneumonia (n=8, 25%). Eleven children (34%) needed intensive care, and the overall death rate was 9% (3/32), with all deaths in patients who had bacteremia. In our center, pediatric iGAS infections carry a substantial comorbidity and disease severity burden, frequently presenting with complex and aggressive clinical manifestations. These findings underscore the urgent need for heightened vigilance in high-risk children, improved diagnostic precision, and strengthened local surveillance systems to enhance prevention and optimize management of these serious infections. Single-center, retrospective design and absence of rapid diagnostic testing.

Many countries saw an increase in invasive infections caused by Streptococcus pyogenes (iGAS) late 2022 to early 2023. Several hypotheses have been put forward to explain this increase, but thus far, reports have been limited to the immediate post-pandemic period, and the relative contribution of each of those factors remains unknown. We describe the epidemiology of iGAS in Belgium in children below 5 years of age from January 2014 until December 2024 based on laboratory data from the National Reference Centre. Using a cointegration analysis after removing seasonality, we formally assess the influence of co-circulating viral diseases varicella, respiratory syncytial virus and influenza on iGAS case numbers. After very low levels during the pandemic years, a marked increase started in June 2022, reaching an all-time high in April 2023 before decreasing but still remaining at high levels in early 2024. Reduced population immunity alone cannot explain this pattern. Emm12, emm1 and emm3 genotypes succeeded each other as the predominant genotype, indicating a complex interplay of transmission and virulence factors. Levels of varicella infections, but not respiratory syncytial virus or influenza, are closely linked to the increase in iGAS levels. Levels of iGAS infections remained high up to 2 years after lifting nonpharmaceutical interventions, and this increase is undoubtedly multifactorial. Continued high-quality surveillance is required to follow up the situation.

Abstract Background Invasive Group A Streptococcus (iGAS) infections have increased recently since the COVID-19 pandemic. This is seen at our institution, Children’s Hospital of Illinois, and via CDC and WHO reporting. Prior to the start of the pandemic, approximately 14,000 to 25,000 cases of iGAS disease occurred in the US each year, with approximately 1,500 to 2,300 deaths.Rate of Complications of GAS/iGAS, pre vs post CoVID-19iGAS Total Admissions and Rate Methods This study was conducted using Epic Cosmos, to obtain hospital encounter data from facilities utilizing Epic across the United States. Data was collected from 2012-2024 on all hospitalized patients. ICD codes related to iGAS infection, ICD codes for complications, age, and state of admission to iGAS infection were collected and reported.iGAS Hospital Admissions by AgeiGAS Crude Case Fatality Rate and Total Deaths Results Data collected spans 40,166,240 hospital admissions. The average yearly admission rate pre and post pandemic is 2,553,308 and 4,296,617, respectively. Average yearly admission rate of iGAS pre and post pandemic was 21,052 and 62,608 respectively. The total number of iGAS admissions is shown to increase since the start of data collection in 2012 (Figure 1), with a steep increase in rate in 2021. There is a 177% increase in the rate of iGAS hospitalizations when comparing pre and post-COVID-19 data. Age data indicate that there is a 1,028% higher rate of iGAS hospitalizations in children less than 10 years old, but all ages show an increased rate of admission post-pandemic (Figure 2). Admission rate increased in all complications from iGAS, ranging from 244-383%, with the highest being in bacteremia (Table 1). Beyond iGAS infections, an increased rate of post Streptococcal nephritic syndromes and rheumatic fever was noted, by 253% and 293%, respectively. With regards to case fatality, the average pre and post pandemic is 10% and 7%, respectively, with a decline starting in 2021 (Figure 3). State data was extracted and showed Ohio having the highest number of pre and post-COVID iGAS admissions at 19,120 and 36,155 cases, respectively. Conclusion This increase in admission rates of iGAS post-COVID-19 pandemic is seen across many studies, including this one. By utilizing Epic Cosmos, we can better approximate iGAS rates across the nation, given estimates of Epic utilization are around 40-50% covering approximately 300 million patients in the US. Disclosures All Authors: No reported disclosures

BackgroundGroup A Streptococcus (GAS) is a known cause of invasive infections (iGAS), with the incidence of GAS pneumonia (GAS PNM) being traditionally low. During the COVID pandemic, the rate of iGAS decreased, followed by a rebound in the years after. Several clusters of GAS PNM were described during this time. Systematic data on GAS PNM epidemiology and outcomes is lacking. In this retrospective study we evaluate the rate of GAS PNM in relation to the pandemic, as well as patient population and outcomes in order to identify risk factors for severe infection.Patients’ recruitmentOf all hospitalized patients between April 1, 2018, and March 31, 2024, with positive Group A Streptococcus (GAS) culture, we identified the patients with invasive GAS infection (iGAS) that was defined as a positive culture from any site other than skin and throat. Among patients with iGAS infection, we identified patients with positive sputum cultures and positive blood cultures. Patients with positive blood culture who had an alternative source of bacteremia were excluded by chart review. Remaining patients with positive blood culture and patients with positive sputum culture were reviewed to confirm the presence of pneumonia on imaging, either CT or chest x-ray*, based on radiology reading. If pneumonia was confirmed on imaging, patients were included in the analysis: 11 patients had both positive blood and sputum culture, 37 only sputum culture and 6 only blood culture, making a total of 56 patients**. GAS= Group A Streptococcus infection; iGAS=invasive Group A Streptococcus infection; Bcx=blood cultures; Cx=culture; PNM=pneumoniaNumber of invasive Group A Streptococcus infection (iGAS) and Group A Streptococcus Pneumonia (GAS PNM) in hospitalized patients in relation to COVID pandemic. iGAS infection is defined as a positive culture isolated from any site other than the skin and throat. GAS PNM is defined as pneumonia on imaging (CT and/or chest x-ray) and either positive sputum culture and/or positive blood culture with no other explanation for GAS bacteremia. The evaluated timeframe was divided into pre-pandemic: April 1, 2018, until March 31, 2020); pandemic (April 1, 2020, until March 31, 2022), and post-pandemic (April 1, 2022, until March 31, 2024). The number of both iGAS and GAS PNM increased in post-pandemic compared with pandemic and pre-pandemic period, although the difference was not statistically significant (p=0.48 and p=0.26, respectively).MethodsAmong patients hospitalized between April 1st, 2018, and March 31st, 2024, in Corewell Health West in Michigan, with positive GAS blood and sputum culture, we identified those with GAS PNM (figure 1). A retrospective chart review was conducted to evaluate patients' characteristics and outcomes defined as hospital and ICU length of stay, 90-day all-cause mortality, and readmission rates. The outcomes were evaluated by the time frame (pre-COVID, COVID, and post-COVID) and mortality status using Chi-squared and Fisher exact tests for categorical and Wilcoxon Rank Sum test for numeric variables to assess statistical significance using an alpha of p< 0.05.Patient characteristics, presentation, clinical course and outcome of Group A Strep pneumonia (GAS PNA) by 90-day mortalityViral coinfection and mortality. Deceased patients were more likely to have viral coinfection on admission (p=0.022).ResultsThe absolute number of GAS PNM increased post-COVID compared with COVID and pre-COVID (Figure 2), but there was no difference in the patients’ characteristics or outcomes among the groups. Overall, 35.7% of patients had a viral coinfection and 66.10% needed ICU level of care with the median ICU stay of 3.21 days (9.1, 0.31-23.56) including 50% of patients requiring ventilator support and 50% of patients experiencing shock requiring vasopressors. 26.8% died within 90 days, with a median time between positive culture and death of 2 days (3.5, 0-59). Deceased patients were more likely to have viral coinfection (p=0.022) and lower WBC (0.0088), and to be febrile (p=0.043) (Figure 3).ConclusionOur data suggests GAS PNM is a severe, rapidly progressive disease, especially with viral coinfection with many patients requiring ICU care with complications including acute renal failure, shock, ventilator dependent respiratory failure, and even death. Recognizing disease early and identifying risk factors for severe disease is vital to improving outcomes.DisclosuresAll Authors: No reported disclosures

BackgroundGroup A Streptococcus pyogenes (GAS) is a leading cause of infectious death globally. Hospital acquired (HA) GAS is particularly burdensome for infection preventionists, administrators, and involved healthcare workers (HCW). After a cluster of fulminant infections (death < / = 48 hrs. from symptom onset), we sought to evaluate the genetic relatedness of the isolates to an HA GAS outbreak that occurred at our facility in 2017and ascertain the genomic epidemiology of invasive GAS (iGAS).Figure 2Heat map showing virulence gene content of 36 Group A Streptococcus isolatesMethodsContact tracing and testing of all HWCs with close contact to any patient with possible HA iGAS and an ambidirectional approach were used. All iGAS one year preceding and one year following the index case were collected and underwent whole genome sequencing (WGS). Medical records of the cases prior and subsequent to the index case were retro- and prospectively reviewed. Additionally, six individual GAS colonies from the throat culture of the only positive HCW were sequenced to assess for intra-colony variation. Results were stratified according to outcome, strain type (ST), and emm type.Table 1Patient and Isolate Characteristics of Fulminant InfectionsResultsFrom 01/01/2023 to 04/01/2025, 40 isolates from 36 patients and the only positive HCW clustered into 13 lineages and 12 emm types. Within each lineage, clusters of high genetic relatedness were identified. However, all isolates from patients with any spatial-temporal or other epidemiologic connection were unrelated, including the ones from the 2017 outbreak (Figure 1). The index isolate belonged to ST-15 emm 3.1. Virulence gene content visually correlated with ST (Figure 2). Although some of isolates from fulminant infections were genetically related, there was no spatial, temporal, or epidemiologic connections among those isolates (Figure 1). There was no association between outcome and ST, or virulence gene content, or antibiotic resistance gene content (Figure 2, Table 1).ConclusionAll iGAS infections, including all fulminant infections, were community acquired. We found no citation explicitly reporting a ST 15 emm sub-type 3.1 in the U.S. Given the elusiveness of iGAS source attribution, these findings illustrate the importance of bolstering community surveillance efforts so that community data can inform outbreak investigation of HA GAS.DisclosuresAll Authors: No reported disclosures

Household contacts of patients with invasive group A streptococcus (iGAS) disease have an increased risk of iGAS. In the Netherlands, the iGAS public health policy was changed in January 2023, offering antibiotic prophylaxis to household contacts of all patients with iGAS rather than only those presenting with necrotizing fasciitis or streptococcal toxic shock syndrome. To estimate risk of iGAS in the general population and among household and other contacts of primary patients with iGAS, before and after the policy change. This nationwide, population-based, open cohort study, linked population registry data with iGAS laboratory data for the study period (April 2022 to December 2024). The study population consisted of all persons included in the Dutch population registry at any time during the study period. The case definition was an iGAS isolate submitted to the Netherlands Reference Laboratory for Bacterial Meningitis, with disease onset in the study period. For contacts of primary patients with iGAS, exposure risk period was defined as the 30 days after culture date of the index patient. Exposure under the new policy was defined as all person-time after January 20, 2023. Incidence rate ratios (IRR) of iGAS during the 30-day risk period compared with unexposed person-time were estimated. Secondary attack rates among household contacts were estimated with an odds ratio (OR) to compare attack rates before and after the policy change. Estimates were adjusted for age group, sex, household socioeconomic status, and year quarter. A total of 19 006 247 persons (9 467 251 male [49.8%]; 6 308 794 [33.2%] aged 20-45 years) contributed 51 067 977 person-years to the analysis. A total of 3644 iGAS isolates from 3630 unique persons were included, of which 14 were household secondary cases. The IRR for household contacts during the risk period was 235.25 (95% CI, 94.35-586.59) before and 74.00 (95% CI, 35.17-155.71) after the policy change, compared with unexposed person-time. The secondary attack rate among household contacts was 0.219% (7 individuals) before and 0.047% (7 individuals) after the policy change (adjusted OR, 0.17; 95% CI, 0.03-0.83). In this nationwide cohort study, there was a reduction in secondary iGAS risk among household contacts after implementation of an expanded antibiotic prophylaxis policy, which suggests that antibiotic prophylaxis for household contacts of patients with iGAS prevents secondary iGAS infection.

Clinical outcome comparison between adjunctive clindamycin vs. linezolid for invasive group A streptococcal infection.

Risk and determinants of mortality associated with invasive group A streptococcus (iGAS) disease in Scotland: A national surveillance study.

Background Cases of invasive group A streptococcal infections (iGAS) increased dramatically in Sweden and other high-income countries during 2023 and 2024. Changing epidemiology and stricter antibiotic stewardship policies are suggested to contribute to this increase. Objectives To describe the clinical presentation and previous health care contacts among cases of iGAS infection over a 5-year period. Methods A retrospective cohort study of iGAS patients treated at Sahlgrenska University Hospital, Gothenburg, Sweden, between January 2020 and July 2024, identified through the hospital’s Clinical Microbiology Laboratory Information System. Data was collected through detailed medical record review by the study team. Results In total, 190 patients with iGAS were included, with the majority (70%, n = 133) treated during 2023–2024. The median age was 53 years (range 1–97) and 51% had no chronic comorbidities. The most common clinical manifestations were erysipelas (22%, n = 42), bacteraemia without focus (21%, n = 39), lower respiratory tract infection (15%, n = 29) and necrotising soft tissue infection (13%, n = 25). Thirty-day mortality was 13% (25/190) with the highest mortality risk for patients with bacteraemia without focus. Relevant health care contacts within 30 days before hospitalisation could be analysed in 167 patientsand was documented in 27% (n = 45) of these cases, most commonly due to a wound (10%, n = 17) or sore throat (9%, n = 15). Conclusion The post-pandemic increase in iGAS affected all age groups. Soft tissue infections remained the dominant type of infection, with erysipelas accounting for around one in four episodes. The iGAS patients had frequently sought care with related complaints shortly before hospitalisation.

BackgroundGroup A Streptococcus causes pediatric infections from mild to severe forms. Since late 2022, invasive cases have increased in Europe, possibly due to reduced post-COVID-19 immunity, more respiratory virus circulation, and emergence of virulent strains.MethodsA retrospective, multicenter observational study was conducted in twelve Italian pediatric Hospitals, including patients under 18 years hospitalized with invasive or severe Group A Streptococcus infection. Data were anonymized and analyzed to identify factors associated with Pediatric Intensive Care Unit (PICU) admission and discharge with sequelae or death.ResultsSeventy-five children with invasive or severe Group A Streptococcus infection were included; the majority (69.3%) were aged 2–10 years. Invasive Group A Streptococcus (iGAS) infection accounted for 58.7% (n = 44) and severe GAS (sGAS) infection for 41.3% (n = 31) of cases. Pediatric Intensive Care Unit admission was required in 45.3% (n = 34) of the entire patient cohort, in this subgroup viral coinfection (OR 5.684, p = 0.003), sepsis/septic shock (OR 4.406, p = 0.003), iGAS diagnosis (OR 4.153, p = 0.005), and procalcitonin (PCT) > 0.5 ng/mL (OR 7.105, p = 0.019) were independently associated with admission; the use of corticosteroids (OR 4.641, p = 0.003) and intravenous immunoglobulin (IVIG) (OR 16.667, p = 0.003) was also significantly more frequent.All patients received empirical β-lactam antibiotics; anti-toxin therapy was administered in 47 patients (62.7%): clindamycin (49.3%), linezolid (16.0%), and rifampicin (1.3%). Mechanical ventilation was required in 24.0% (n = 18), and 49.3% (n = 37) underwent surgery. Post-infectious sequelae occurred in 20.0% (n = 15) and four children died, mostly due to streptococcal toxic shock syndrome.ConclusionPediatric invasive group A streptococcal infection continues to pose a significant clinical challenge, with notable rates of morbidity and mortality, underscoring the need for early recognition and close monitoring of high-risk patients. A widespread use of adjunctive therapies was documented. Continued surveillance and robust clinical research are essential to optimize management strategies and improve patient outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13052-025-02103-7.

PurposeThis study aimed to describe the molecular epidemiology and antimicrobial susceptibility profiles of invasive (iGAS) and non-invasive (non-iGAS) Group A Streptococcus (GAS) isolates collected from Greek children, including all the Greek fatal pediatric GAS infections, in 2023.MethodsGAS isolates were prospectively collected from children (0–16 years) with iGAS and non-iGAS infections from January to December 2023. Antimicrobial susceptibility was examined with the disk diffusion method and the MIC of resistant isolates was determined. Emm typing was performed in all isolates. Whole genome analysis was performed on emm1 GAS isolates collected from fatal cases.ResultsGAS isolates from 510 children, with median (IQR) age: 67.8 (46.1–96.0) months, were analyzed in the study. There were 30 (5.9%) iGAS cases, of which nine were fatal. All isolates were penicillin-susceptible, while the resistance rates to tetracycline, erythromycin, and clindamycin were 16.9%, 11.6% and 5.1%, respectively. The M, cMLSB and iMLSB phenotypes were found in 33/510 (6.5%), 22/510 (4.3%) and 4/510 (0.8%) isolates, respectively. Thirty-two emm types were detected, with the most prevalent being emm12 (41.0%), emm1 (26.9%) and emm89 (7.5%). Among the different emm types, emm1 was marginally associated with iGAS. The emm12 type was associated with resistance to clindamycin (p = 0.039). GAS isolates from the nine deceased children p-value were identified as emm1 (7/9), of which 6/7 belonged to M1UK lineage, and emm12 (2/9).ConclusionA predominance of emm12 and emm1 was detected in non-iGAS isolates and of emm1 in iGAS isolates, and specifically M1UK in fatal isolates. A decline in GAS macrolide resistance, compared to previous studies in our area, was detected.Supplementary InformationThe online version contains supplementary material available at 10.1007/s15010-025-02639-0.