A Case Series of Noninvasive (non-iGAS) and Invasive (iGAS) Pediatric Group A Streptococcal Infections at a Tertiary Healthcare Center: Resurgence and Concomitant Viral Infections

A Case Series of Noninvasive (non-iGAS) and Invasive (iGAS) Pediatric Group A Streptococcal Infections at a Tertiary Healthcare Center: Resurgence and Concomitant Viral Infections | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Case Series of Noninvasive (non-iGAS) and Invasive (iGAS) Pediatric Group A Streptococcal Infections at a Tertiary Healthcare Center: Resurgence and Concomitant Viral Infections Susan Fields, Caroline Butler, Sarah Fowler, Srilatha Neshangi, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4397131/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background After a decrease in pediatric invasive group A streptococcal cases during the peak of the COVID-19 infection isolation guidelines in 2020 and 2021, the Centers for Disease Control and Prevention (CDC) documented a surge in cases in multiple states across the United States during late 2022. Methods We performed a retrospective chart review exploring both invasive pediatric group A streptococcal infections (iGAS) and noninvasive group A streptococcal infections (non-iGAS) admissions to the Children’s Hospital of Georgia from July 1, 2021 to June 30, 2023. Demographics, seasonality, concomitant viral and bacterial infections, antibiotic use preferences, pediatric intensive care (PICU) admission, and mortality were included. Results We found a substantial increase in both iGAS and non-iGAS cases during the study time. Most patients with iGAS presented were teenagers, white, and had sepsis and bacteremia. Non iGAS patients were not older than 11 years of age, were predominantly back, and had complicated pneumonia. Influenza was the most common concomitant virus seen in invasive and noninvasive cases, but our sample also included infections with respiratory syncytial virus (RSV), metapneumovirus (HMPV), rhinovirus and adenovirus among others. Methicillin-sensitive staphylococcus (MSSA) aureus was the most common bacteria seen in patients with both invasive and noninvasive disease. Treatment optimization was only achieved after pediatric Infectious Diseases consultation. Conclusions The surge in noninvasive and invasive pediatric GAS disease seen at our institution matched the end of COVID-19 infection masking policies in the United States. This drastic rise should be recognized, and surveillance should be reinforced. Increased knowledge and understanding of this surge in group A streptococcal infections will allow for early intervention and treatment, thereby reducing morbidity and mortality. Invasive Group A Streptococcus Non-Invasive Group A Streptococcus COVID-19 Influenza Antibiotic stewardship Figures Figure 1 Figure 2 BACKGROUND Group A streptococci (GAS) is a gram-positive cocci in chains with over 100 subtypes based on M protein presence. The disease incubation period is 2–5 days. GAS infections from a non-sterile body site are defined as non-invasive GAS disease (non-iGAS). Invasive GAS (iGAS) disease corresponds to specimens isolated by culture from a sterile body site, including blood, pleural fluid, peritoneal fluid, cerebrospinal fluid, joint fluid or bone, GAS isolated from a necrotizing fasciitis wound culture, or streptococcal toxic shock syndrome (STSS) [1]. In the United States, iGAS pediatric cases had been relatively consistent from the mid-1990s to 2019, with 100 to 200 cases per year [2]. Only 74 pediatric iGAS cases were documented in 2020, believed to be due to social distancing and masking during the COVID-19 pandemic [3]. However, in December 2022, the Centers for Disease Control and Prevention (CDC) issued a health advisory regarding an increase in pediatric iGAS cases reported in Minnesota and Colorado during the fall months of 2022 [4]. MATERIALS AND METHODS We conducted a retrospective chart review on patients ages 6 months old to 18 years old admitted to the Children’s Hospital of Georgia, a tertiary healthcare center in Augusta, GA, comparing cases of iGAS and non-iGAS infections diagnosed from mid 2021 to mid 2023. Our analytic sample included a total of 28 children, 14 had non-iGAS infections and 14 had iGAS infection (positive peritoneal and pleural fluid, joint/bone aspirates, bronchoalveolar lavage samples, and blood cultures). Demographics, site of infection, concomitant viral infections diagnosed by nasopharyngeal (NP) polymerase chain reaction (PCR), associated bacterial infections, antibiotic usage, and mortality data from the pediatric intensive care unit (PICU) and the pediatric floor were collected. RESULTS From July 1, 2021 to June 30, 2022, only 1 patient was admitted with a proven GAS infection, an iGAS case diagnosed with a leg abscess and subsequent progression to sepsis with GAS isolated from peritoneal fluid. Comparatively, from July 1, 2022 to June 30, 2023, there was a sharp increase both iGAS and non-iGAS cases. During this time, 27 patients were admitted with GAS infections – 13 with iGAS infections and 14 with non-iGAS infections. Most invasive cases occurred in patients between 12–15 years old while those with noninvasive disease were younger (8–11 years old). In both groups, there was a male predominance. Most non-iGAS patients were black and the majority of iGAS patients were white. For both groups, GAS disease peaked in the winter. Only one patient with invasive disease died, and the cause of mortality was sepsis secondary to septic arthritis of the joint (Table 1 ). Table 1 Demographics, seasonality, admission location and length of stay of iGAS and non-iGAS cases admitted to the Children’s Hospital of Georgia from July 1, 2021 to June 30, 2023. Characteristics of Admitted GAS Cases iGAS n = 14 non-iGAS n = 14 Age 0–3 y/o 2 (14.3%) 3 (21.4%) 4–7 y/o 2 (14.3%) 2 (14.3%) 8–11 y/o 3 (21.4%) 9 (64.3%) 12–15 y/o 4 (28.6%) 0 (0.0%) 16–18 y/o 3 (21.4%) 0 (0.0%) Sex Male 8 (57.1%) 10 (71.4%) Female 6 (42.9%) 4 (28.6%) Race White 10 (71.4%) 3 (21.4%) Black 4 (28.6%) 8 (57.1%) Hispanic 0 (0.0%) 1 (7.1%) Unspecified 0 (0.0%) 2 (14.3%) Seasonality Winter 5 (35.7%) 7 (50.0%) Spring 4 (28.6%) 3 (21.4%) Summer 2 (14.3%) 1 (7.1%) Fall 3 (21.4%) 3 (21.4%) Year July1, 2021 – June 30, 2022 1 (7.1%) 0 (0.0%) July 1, 2022 – June 30, 2023 13 (92.9%) 14 (100.0%) Admission Location ICU 7 (50.0%) 5 (35.7%) Floor 7 (50.0%) 9 (64.3%) Length of Stay 1–7 days 5 (35.7%) 11 (78.6%) 8–14 days 7 (50.0%) 0 (0.0%) 15–30 days 2 (14.3%) 2 (14.3%) > 30 days 0 (0.0%) 1 (7.1%) GAS-related Deaths 1 (7.1%) 0 (0.0%) Table 1 Abbreviations: GAS, group A streptococcus; iGAS, invasive group A streptococcus; non-iGAS, noninvasive group A streptococcus; y/o, years old; ICU, intensive care unit Influenza was the predominant virus associated with GAS infections, 21% of cases in both iGAS and non-iGAS groups tested positive by nasal sample PCR. All cases of concomitant influenza infection occurred between the months of October to January, correlating with influenza circulation in the northern hemisphere. Additionally, in patients with non-iGAS infection, one tested positive for respiratory syncytial virus (RSV), two patients had rhinovirus, one had adenovirus. One patient with iGAS infection tested positive for metapneumovirus (HMPV) (Fig. 1). Except for one patient who presented with non-iGAS infection and concomitant rhinovirus and RSV in July, all other viruses found in both iGAS and non-iGAS groups were also seen between the months of October to January. Figure 1 Concomitant viruses found in both iGAS and non-iGAS cases admitted to the Children’s Hospital of Georgia from July 1, 2021 to June 30, 2023. Figure 1 Abbreviations: GAS, group A streptococcus; iGAS, invasive group A streptococcus; non-iGAS, noninvasive group A streptococcus More than half of patients with iGAS disease presented with GAS bacteremia. 35.7% of iGAS cases had GAS pneumonia and one non-iGAS case had Methicillin Sensitive Staphylococcus Aureus (MSSA) pneumonia. 21% of iGAS cases evolved into STSS. The most common concomitant bacterial infection in both iGAS and non-iGAS infections was MSSA. Clindamycin was predominantly used in patients with iGAS infections in the first 48 hours of admission in combination with vancomycin and ceftriaxone. In these cases, penicillin was added only after 48 hours. In non-invasive GAS patients, ampicillin/sulbactam and ceftriaxone were most used during the first 48 hours (Fig. 2). Figure 2 Antimicrobials used for invasive and noninvasive GAS cases in the first 48 hours from admission compared to after 48 hours from admission to the Children’s Hospital of Georgia from July 1, 2021 to June 30, 2023. Figure 2 Abbreviations: GAS, group A streptococcus; iGAS, invasive group A streptococcus; non-iGAS, noninvasive group A streptococcus, PCN G, Penicillin G DISCUSSION The surge in our iGAS cases relates to a similar World Health Organization (WHO) report of increased iGAS cases in the second half of 2022 in Europe, as well as the CDC reports from the fall of 2022 in Colorado and Minnesota [3,4]. In the state of Georgia, local government ended mask mandates in August 2021, but the CDC only removed mask orders on public transportation in April 2022. Our noninvasive cases matched the rise in invasive GAS cases, no other studies have reported non-iGAS and iGAS disease admissions during this timeframe. The age distribution of iGAS infections in our study correlates with prior US reports, seen in all ages with older children predominance [5]. iGAS cases in Europe were reported in children under 10-year-old which matches our non-iGAS infections age distribution [ 6 ] . Also consistent with prior reports, invasive and non-invasive GAS cases were more common in males, most cases occurred during winter or early spring, and the majority of iGAS cases occurred in white children and non-iGAS cases in black children [5, 7]. Concomitant GAS and influenza virus infections are known to be associated with excess morbidity and mortality [8]. Most of our patients with iGAS and influenza were admitted to the PICU; however, all patients with non-iGAS and influenza were admitted to the floor. Patients with iGAS and non-iGAS infections and influenza had a longer mean length of stay compared to those without influenza. iGAS patients with and without influenza were admitted for 14.3 days vs 7.7 days, respectively, and non-iGAS patients with and without influenza were admitted for 12.6 days vs 5.9 days, respectively. These findings are consistent with prior literature showing an increased length of stay in patients with influenza coinfection [9]. The above findings could be related to virus-induced adaptations in innate immunity, and variation in bacterial adherence and internalization following viral infections. Interestingly, none of the patients admitted with iGAS or non-iGAS infections tested positive for COVID-19 infection during their hospital stay. Previous literature has shown that the most common causes of bacteremia in the pediatric population over three months of age include Streptococcus pneumoniae, Staphylococcus aureus , and Escherichia coli ; GAS bacteremia has a low overall incidence in the pediatric population [10]. However, more than half of our patients with iGAS were bacteremic and over a third were also diagnosed with pneumonia. Concomitant bacteria were discovered in both iGAS and non-iGAS infection patients; MSSA was the most common pathogen for both groups, and it was mostly collected from tracheal aspirates. Three patients with iGAS infection evolved into STSS. Penicillin is the treatment of choice for iGAS infections. Combination therapy of penicillin and clindamycin is a more effective regimen; however, clindamycin should not be used as monotherapy due to increasing resistance [11]. The most common combinations in the first 48 hours of admission for iGAS infections were vancomycin, ceftriaxone, and clindamycin despite clear recommendations to use penicillin. The broad-spectrum coverage was probably due to the uncertainty of the diagnosis at time of admission. Like iGAS treatment, a penicillin is the first line treatment for most non-invasive GAS cases. Non-invasive GAS cases within the first 48 hours of admission received ampicillin/sulbactam and ceftriaxone. The use of ampicillin/sulbactam as monotherapy in patients with non-invasive GAS infections remains unclear to us. Penicillin was never administered to patients with non-invasive disease. The variation in antimicrobials administered to both invasive and non-invasive GAS patients open a conversation surrounding low adherence to antibacterial standard of care options in patients with GAS infections. Infectious Disease consultations were placed on average on day 3 of admission in invasive cases compared to day 8.5 in non-invasive cases. These Infectious Disease consultations resulted in the use of standardized regimens of clindamycin and penicillin G for iGAS infections. Prior studies demonstrate that early infectious disease consultations lead to improved clinical outcomes [12]. CONCLUSION Our results show that the surge in noninvasive and invasive pediatric GAS disease matched the end of COVID-19 infection masking policies in the United States. This drastic rise in pediatric GAS cases should not go unnoticed. GAS infections resurgence should prompt efforts to improve early detection and surveillance, thereby limiting morbidity and mortality. The significant presence of influenza infections in patients with iGAS ratifies the importance of improving vaccination rates in pediatric patients. Antimicrobial stewardship efforts at our institution should be strengthened. Declarations Human ethics approval: Approval for data collection and research was approved by the Institutional Review Board at Augusta University. Consent to participate: Not applicable, this was a retrospective chart review approved by the Institutional Review Board at Augusta University. Consent for publication : Not applicable, this was a retrospective chart review approved by the Institutional Review Board at Augusta University. Availability of data and materials: Data was pulled using BioMerieux software to obtain MRNs of patient’s admitted with GAS infection from July 1, 2021 to June 30, 2023. The complete datasets generated and analyzed during the current study are not publicly available because they contain confidential patient health information but are available from the corresponding author on reasonable request. Competing interests: Not applicable Funding: Not applicable Authors' contributions: S.F., C.B., and S.F. analyzed and interpreted patient data, wrote the main manuscript text, and prepared the table/figures. S.N. and I.G. provided guidance and review of the manuscript. Acknowledgements: Not applicable We do not have an association that might pose a conflict of interest. Susan Fields, BS, no conflict Caroline Butler, BS, no conflict Sarah Fowler, BA, no conflict Srilatha Neshangi, MBBS, MPH, no conflict Ingrid Camelo, MD, MPH, no conflict References Case definitions for infectious conditions under public health surveillance. Centers for Disease Control and Prevention. MMWR Recomm Rep . 1997;46(RR-10):1-55. Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/00047449.htm Centers for Disease Control and Prevention. Active Bacterial Core Surveillance (ABCs). ABCs Report: group A Streptococcus, 2019. Available at: https://www.cdc.gov/abcs/downloads/GAS_Surveillance_Report_2019.pdf. Accessed 22 December 2022. Centers for Disease Control and Prevention. Active Bacterial Core Surveillance (ABCs). ABCs Report: group A Streptococcus, 2020. Available at: https://www.cdc.gov/abcs/downloads/GAS_Surveillance_Report_2020.pdf. Accessed 22 December 2022. Barnes M, Youngkin E, Zipprich J, et al. Notes from the Field: Increase in Pediatric Invasive Group A Streptococcus Infections — Colorado and Minnesota, October–December 2022. MMWR Morb Mortal Wkly Rep 2023;72:265–267. doi: http://dx.doi.org/10.15585/mmwr.mm7210a4 Factor SH, Levine OS, Harrison LH, et al. Risk factors for pediatric invasive group A streptococcal disease. Emerg Infect Dis . 2005;11(7):1062-1066. doi:10.3201/eid1107.040900 World Health Organization. (12 December 2022). Increase in invasive group A streptococcal infections among children in Europe, including fatalities. Available at: https://www.who.int/europe/news/item/12-12-2022-increase-in-invasive-group-a-streptococcal-infections-among-children-in-europe--including-fatalities Acute Communicable Disease Control. Invasive Group A Streptococcus. 2002. Available at: http://publichealth.lacounty.gov/acd/Diseases/Strepto_IGAS_02.pdf. Accessed 10 November 2023. Herrera AL, Huber VC, Chaussee MS. The Association between Invasive Group A Streptococcal Diseases and Viral Respiratory Tract Infections. Front Microbiol. 2016 Mar 21;7:342. doi: 10.3389/fmicb.2016.00342. Martin-Loeches I, Lemiale V, Geoghegan P, et al. Influenza and associated co-infections in critically ill immunosuppressed patients. Crit Care. 2019 May 2;23(1):152. doi: 1.1186/s13054-019-2425-6. Ferreira M, Santos M, Rodrigues J, et al. Epidemiology of bacteremia in a pediatric population - A 10-year study. Enferm Infecc Microbiol Clin (Engl Ed) . Published online July 15, 2021. doi:10.1016/j.eimc.2021.06.011 Allen U, Moore D. Invasive group A streptococcal disease: Management and chemoprophylaxis. Paediatr Child Health . 2010;15(5):295-302. Cole JC, Jankowski CA, Verdecia JL, Isache CL, Ravi MS, McCarter YS, Casapao AM. The Time for Action Is Now: The Impact of Timing of Infectious Disease Consultation for Staphylococcus aureus Bacteremia. Clin Infect Dis. 2023 Jun 8;76(11):2007-2009. doi: 10.1093/cid/ciad110. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4397131","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":315652106,"identity":"9ce71ff9-0d1f-43ae-b5ba-502198ecac2c","order_by":0,"name":"Susan Fields","email":"","orcid":"","institution":"Augusta University","correspondingAuthor":false,"prefix":"","firstName":"Susan","middleName":"","lastName":"Fields","suffix":""},{"id":315652108,"identity":"2ad16089-e628-40dd-a5eb-8c0dbf34adab","order_by":1,"name":"Caroline Butler","email":"","orcid":"","institution":"Augusta University","correspondingAuthor":false,"prefix":"","firstName":"Caroline","middleName":"","lastName":"Butler","suffix":""},{"id":315652110,"identity":"b9a38fb7-2913-4353-8de1-8897fa3bf590","order_by":2,"name":"Sarah Fowler","email":"","orcid":"","institution":"Augusta University","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"","lastName":"Fowler","suffix":""},{"id":315652112,"identity":"90133ed7-a9eb-4fab-b193-0280a4858c97","order_by":3,"name":"Srilatha Neshangi","email":"","orcid":"","institution":"Augusta University","correspondingAuthor":false,"prefix":"","firstName":"Srilatha","middleName":"","lastName":"Neshangi","suffix":""},{"id":315652113,"identity":"5c161273-e10a-4792-b5b6-e4cd96109153","order_by":4,"name":"Ingrid Camelo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYBACNjBZwCCHJJZAjBYDBmMk1QS0MEC1JDYQrYWP/fDTDR8MbNL7Z6Rfk/z5w46Bnz3HAL/DeNLMbs4wSMudcSOnTJonIZlBsucNAS0SDGa3eQwO5zbcyEmTZkhgZjC4QcgWCfZvt/8YHE6XB2qR/JFQz2BPWAuP2W0Gg8MJBjfSj0nwJBxmMJAg6Jecsps9BmmGG8+8YbbmSTvOI3HmWQFeLfLtx7fd+FFhIy93PP3hzR821XL87ckb8GpBAjxg9/AQqxwE2B+QonoUjIJRMApGEAAA9ENC4H3NGEIAAAAASUVORK5CYII=","orcid":"","institution":"Augusta University","correspondingAuthor":true,"prefix":"","firstName":"Ingrid","middleName":"","lastName":"Camelo","suffix":""}],"badges":[],"createdAt":"2024-05-09 21:09:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4397131/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4397131/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":59049295,"identity":"e101e43e-a9e7-43d1-b4db-2a2e45951baa","added_by":"auto","created_at":"2024-06-25 19:32:56","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":84701,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eConcomitant viruses found in both iGAS and non-iGAS cases admitted to the Children’s Hospital of Georgia from July 1, 2021 to June 30, 2023.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations: GAS, group A streptococcus; iGAS, invasive group A streptococcus; non-iGAS, noninvasive group A streptococcus\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4397131/v1/74a5c9333982b72165f4dc3d.jpg"},{"id":59049294,"identity":"0500c2a7-ea63-42fb-8a31-98525e26998f","added_by":"auto","created_at":"2024-06-25 19:32:56","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":105559,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eAntimicrobials used for invasive and noninvasive GAS cases in the first 48 hours from admission compared to after 48 hours from admission to the Children’s Hospital of Georgia from July 1, 2021 to June 30, 2023.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;Abbreviations: GAS, group A streptococcus; iGAS, invasive group A streptococcus; non-iGAS, noninvasive group A streptococcus, PCN G, Penicillin G\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4397131/v1/790088dc487cb109cbb47dc6.jpg"},{"id":59548697,"identity":"b56f3e96-9893-43ac-b5ef-6ba415df3822","added_by":"auto","created_at":"2024-07-03 05:48:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":601001,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4397131/v1/466c056f-2b24-4b4c-936c-99e93ff80a23.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Case Series of Noninvasive (non-iGAS) and Invasive (iGAS) Pediatric Group A Streptococcal Infections at a Tertiary Healthcare Center: Resurgence and Concomitant Viral Infections","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003e \u003cem\u003eGroup A streptococci\u003c/em\u003e (GAS) is a gram-positive cocci in chains with over 100 subtypes based on M protein presence. The disease incubation period is 2\u0026ndash;5 days. GAS infections from a non-sterile body site are defined as non-invasive GAS disease (non-iGAS). Invasive GAS (iGAS) disease corresponds to specimens isolated by culture from a sterile body site, including blood, pleural fluid, peritoneal fluid, cerebrospinal fluid, joint fluid or bone, GAS isolated from a necrotizing fasciitis wound culture, or streptococcal toxic shock syndrome (STSS) [1].\u003c/p\u003e \u003cp\u003eIn the United States, iGAS pediatric cases had been relatively consistent from the mid-1990s to 2019, with 100 to 200 cases per year [2]. Only 74 pediatric iGAS cases were documented in 2020, believed to be due to social distancing and masking during the COVID-19 pandemic [3]. However, in December 2022, the Centers for Disease Control and Prevention (CDC) issued a health advisory regarding an increase in pediatric iGAS cases reported in Minnesota and Colorado during the fall months of 2022 [4].\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003e We conducted a retrospective chart review on patients ages 6 months old to 18 years old admitted to the Children\u0026rsquo;s Hospital of Georgia, a tertiary healthcare center in Augusta, GA, comparing cases of iGAS and non-iGAS infections diagnosed from mid 2021 to mid 2023. Our analytic sample included a total of 28 children, 14 had non-iGAS infections and 14 had iGAS infection (positive peritoneal and pleural fluid, joint/bone aspirates, bronchoalveolar lavage samples, and blood cultures). Demographics, site of infection, concomitant viral infections diagnosed by nasopharyngeal (NP) polymerase chain reaction (PCR), associated bacterial infections, antibiotic usage, and mortality data from the pediatric intensive care unit (PICU) and the pediatric floor were collected.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eFrom July 1, 2021 to June 30, 2022, only 1 patient was admitted with a proven GAS infection, an iGAS case diagnosed with a leg abscess and subsequent progression to sepsis with GAS isolated from peritoneal fluid. Comparatively, from July 1, 2022 to June 30, 2023, there was a sharp increase both iGAS and non-iGAS cases. During this time, 27 patients were admitted with GAS infections \u0026ndash; 13 with iGAS infections and 14 with non-iGAS infections.\u003c/p\u003e \u003cp\u003eMost invasive cases occurred in patients between 12\u0026ndash;15 years old while those with noninvasive disease were younger (8\u0026ndash;11 years old). In both groups, there was a male predominance. Most non-iGAS patients were black and the majority of iGAS patients were white. For both groups, GAS disease peaked in the winter. Only one patient with invasive disease died, and the cause of mortality was sepsis secondary to septic arthritis of the joint (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographics, seasonality, admission location and length of stay of iGAS and non-iGAS cases admitted to the Children\u0026rsquo;s Hospital of Georgia from July 1, 2021 to June 30, 2023.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCharacteristics of Admitted GAS Cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eiGAS\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;14\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003enon-iGAS\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;14\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u0026ndash;3 y/o\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u0026ndash;7 y/o\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u0026ndash;11 y/o\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (64.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u0026ndash;15 y/o\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u0026ndash;18 y/o\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eRace\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBlack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eSeasonality\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWinter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (35.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpring\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSummer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eYear\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJuly1, 2021 \u0026ndash; June 30, 2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJuly 1, 2022 \u0026ndash; June 30, 2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (92.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14 (100.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eAdmission Location\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eICU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (35.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFloor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (64.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eLength of Stay\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;7 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (35.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11 (78.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u0026ndash;14 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u0026ndash;30 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;30 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGAS-related Deaths\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u003cem\u003eAbbreviations: GAS, group A streptococcus; iGAS, invasive group A streptococcus; non-iGAS, noninvasive group A streptococcus; y/o, years old; ICU, intensive care unit\u003c/em\u003e\u003c/p\u003e \u003cp\u003eInfluenza was the predominant virus associated with GAS infections, 21% of cases in both iGAS and non-iGAS groups tested positive by nasal sample PCR. All cases of concomitant influenza infection occurred between the months of October to January, correlating with influenza circulation in the northern hemisphere. Additionally, in patients with non-iGAS infection, one tested positive for respiratory syncytial virus (RSV), two patients had rhinovirus, one had adenovirus. One patient with iGAS infection tested positive for metapneumovirus (HMPV) (Fig.\u0026nbsp;1). Except for one patient who presented with non-iGAS infection and concomitant rhinovirus and RSV in July, all other viruses found in both iGAS and non-iGAS groups were also seen between the months of October to January.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eFigure 1\u003c/strong\u003e \u003cp\u003e \u003cem\u003eConcomitant viruses found in both iGAS and non-iGAS cases admitted to the Children\u0026rsquo;s Hospital of Georgia from July 1, 2021 to June 30, 2023.\u003c/em\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eFigure 1 Abbreviations: GAS, group A streptococcus; iGAS, invasive group A streptococcus; non-iGAS, noninvasive group A streptococcus\u003c/em\u003e \u003c/p\u003e \u003cp\u003eMore than half of patients with iGAS disease presented with GAS bacteremia. 35.7% of iGAS cases had GAS pneumonia and one non-iGAS case had Methicillin Sensitive Staphylococcus Aureus (MSSA) pneumonia. 21% of iGAS cases evolved into STSS. The most common concomitant bacterial infection in both iGAS and non-iGAS infections was MSSA.\u003c/p\u003e \u003cp\u003eClindamycin was predominantly used in patients with iGAS infections in the first 48 hours of admission in combination with vancomycin and ceftriaxone. In these cases, penicillin was added only after 48 hours. In non-invasive GAS patients, ampicillin/sulbactam and ceftriaxone were most used during the first 48 hours (Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eFigure 2\u003c/strong\u003e \u003cp\u003e \u003cem\u003eAntimicrobials used for invasive and noninvasive GAS cases in the first 48 hours from admission compared to after 48 hours from admission to the Children\u0026rsquo;s Hospital of Georgia from July 1, 2021 to June 30, 2023.\u003c/em\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eFigure 2 Abbreviations: GAS, group A streptococcus; iGAS, invasive group A streptococcus; non-iGAS, noninvasive group A streptococcus, PCN G, Penicillin G\u003c/em\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe surge in our iGAS cases relates to a similar World Health Organization (WHO) report of increased iGAS cases in the second half of 2022 in Europe, as well as the CDC reports from the fall of 2022 in Colorado and Minnesota [3,4]. In the state of Georgia, local government ended mask mandates in August 2021, but the CDC only removed mask orders on public transportation in April 2022. Our noninvasive cases matched the rise in invasive GAS cases, no other studies have reported non-iGAS and iGAS disease admissions during this timeframe.\u003c/p\u003e \u003cp\u003eThe age distribution of iGAS infections in our study correlates with prior US reports, seen in all ages with older children predominance [5]. iGAS cases in Europe were reported in children under 10-year-old which matches our non-iGAS infections age distribution \u003csup\u003e[\u003c/sup\u003e6\u003csup\u003e]\u003c/sup\u003e. Also consistent with prior reports, invasive and non-invasive GAS cases were more common in males, most cases occurred during winter or early spring, and the majority of iGAS cases occurred in white children and non-iGAS cases in black children [5, 7].\u003c/p\u003e \u003cp\u003eConcomitant GAS and influenza virus infections are known to be associated with excess morbidity and mortality [8]. Most of our patients with iGAS and influenza were admitted to the PICU; however, all patients with non-iGAS and influenza were admitted to the floor. Patients with iGAS and non-iGAS infections and influenza had a longer mean length of stay compared to those without influenza. iGAS patients with and without influenza were admitted for 14.3 days vs 7.7 days, respectively, and non-iGAS patients with and without influenza were admitted for 12.6 days vs 5.9 days, respectively. These findings are consistent with prior literature showing an increased length of stay in patients with influenza coinfection [9]. The above findings could be related to virus-induced adaptations in innate immunity, and variation in bacterial adherence and internalization following viral infections. Interestingly, none of the patients admitted with iGAS or non-iGAS infections tested positive for COVID-19 infection during their hospital stay.\u003c/p\u003e \u003cp\u003ePrevious literature has shown that the most common causes of bacteremia in the pediatric population over three months of age include \u003cem\u003eStreptococcus pneumoniae, Staphylococcus aureus\u003c/em\u003e, and \u003cem\u003eEscherichia coli\u003c/em\u003e; GAS bacteremia has a low overall incidence in the pediatric population [10]. However, more than half of our patients with iGAS were bacteremic and over a third were also diagnosed with pneumonia. Concomitant bacteria were discovered in both iGAS and non-iGAS infection patients; MSSA was the most common pathogen for both groups, and it was mostly collected from tracheal aspirates. Three patients with iGAS infection evolved into STSS.\u003c/p\u003e \u003cp\u003ePenicillin is the treatment of choice for iGAS infections. Combination therapy of penicillin and clindamycin is a more effective regimen; however, clindamycin should not be used as monotherapy due to increasing resistance [11]. The most common combinations in the first 48 hours of admission for iGAS infections were vancomycin, ceftriaxone, and clindamycin despite clear recommendations to use penicillin. The broad-spectrum coverage was probably due to the uncertainty of the diagnosis at time of admission.\u003c/p\u003e \u003cp\u003eLike iGAS treatment, a penicillin is the first line treatment for most non-invasive GAS cases. Non-invasive GAS cases within the first 48 hours of admission received ampicillin/sulbactam and ceftriaxone. The use of ampicillin/sulbactam as monotherapy in patients with non-invasive GAS infections remains unclear to us. Penicillin was never administered to patients with non-invasive disease.\u003c/p\u003e \u003cp\u003e The variation in antimicrobials administered to both invasive and non-invasive GAS patients open a conversation surrounding low adherence to antibacterial standard of care options in patients with GAS infections. Infectious Disease consultations were placed on average on day 3 of admission in invasive cases compared to day 8.5 in non-invasive cases. These Infectious Disease consultations resulted in the use of standardized regimens of clindamycin and penicillin G for iGAS infections. Prior studies demonstrate that early infectious disease consultations lead to improved clinical outcomes [12].\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eOur results show that the surge in noninvasive and invasive pediatric GAS disease matched the end of COVID-19 infection masking policies in the United States. This drastic rise in pediatric GAS cases should not go unnoticed. GAS infections resurgence should prompt efforts to improve early detection and surveillance, thereby limiting morbidity and mortality. The significant presence of influenza infections in patients with iGAS ratifies the importance of improving vaccination rates in pediatric patients. Antimicrobial stewardship efforts at our institution should be strengthened.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eHuman ethics approval:\u0026nbsp;\u003c/strong\u003eApproval for data collection and research was approved by the Institutional Review Board at Augusta University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e Not applicable, this was a retrospective chart review approved by the Institutional Review Board at Augusta University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable, this was a retrospective chart review approved by the Institutional Review Board at Augusta University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eData was pulled using\u0026nbsp;BioMerieux software to obtain MRNs of patient\u0026rsquo;s admitted with GAS infection from July 1, 2021 to June 30, 2023. The complete datasets generated and analyzed during the current study are not publicly available because they contain confidential patient health information but are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003eS.F., C.B., and S.F. analyzed and interpreted patient data, wrote the main manuscript text, and prepared the table/figures. S.N. and I.G. provided guidance and review of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWe do not have an association that might pose a conflict of interest.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSusan Fields, BS,\u003c/strong\u003e no conflict\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCaroline Butler, BS,\u003c/strong\u003e no conflict\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSarah Fowler, BA,\u003c/strong\u003e no conflict\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSrilatha Neshangi, MBBS, MPH,\u003c/strong\u003e no conflict\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIngrid Camelo, MD, MPH,\u003c/strong\u003e no conflict\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCase definitions for infectious conditions under public health surveillance. Centers for Disease Control and Prevention. \u003cem\u003eMMWR Recomm Rep\u003c/em\u003e. 1997;46(RR-10):1-55. Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/00047449.htm\u003c/li\u003e\n\u003cli\u003eCenters for Disease Control and Prevention. Active Bacterial Core Surveillance (ABCs). ABCs Report: group A Streptococcus, 2019. Available at: https://www.cdc.gov/abcs/downloads/GAS_Surveillance_Report_2019.pdf. Accessed 22 December 2022.\u003c/li\u003e\n\u003cli\u003eCenters for Disease Control and Prevention. Active Bacterial Core Surveillance (ABCs). ABCs Report: group A Streptococcus, 2020. Available at: https://www.cdc.gov/abcs/downloads/GAS_Surveillance_Report_2020.pdf. Accessed 22 December 2022.\u003c/li\u003e\n\u003cli\u003eBarnes M, Youngkin E, Zipprich J, et al. \u003cem\u003eNotes from the Field:\u003c/em\u003e Increase in Pediatric Invasive Group A \u003cem\u003eStreptococcus\u003c/em\u003e Infections \u0026mdash; Colorado and Minnesota, October\u0026ndash;December 2022. MMWR Morb Mortal Wkly Rep 2023;72:265\u0026ndash;267. doi: http://dx.doi.org/10.15585/mmwr.mm7210a4\u003c/li\u003e\n\u003cli\u003eFactor SH, Levine OS, Harrison LH, et al. Risk factors for pediatric invasive group A streptococcal disease. \u003cem\u003eEmerg Infect Dis\u003c/em\u003e. 2005;11(7):1062-1066. doi:10.3201/eid1107.040900\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. (12 December 2022). Increase in invasive group A streptococcal infections among children in Europe, including fatalities. Available at: https://www.who.int/europe/news/item/12-12-2022-increase-in-invasive-group-a-streptococcal-infections-among-children-in-europe--including-fatalities\u003c/li\u003e\n\u003cli\u003eAcute Communicable Disease Control. Invasive Group A Streptococcus. 2002. Available at: http://publichealth.lacounty.gov/acd/Diseases/Strepto_IGAS_02.pdf. Accessed 10 November 2023.\u003c/li\u003e\n\u003cli\u003eHerrera AL, Huber VC, Chaussee MS. The Association between Invasive Group A Streptococcal Diseases and Viral Respiratory Tract Infections. Front Microbiol. 2016 Mar 21;7:342. doi: 10.3389/fmicb.2016.00342. \u003c/li\u003e\n\u003cli\u003eMartin-Loeches I, Lemiale V, Geoghegan P, et al. Influenza and associated co-infections in critically ill immunosuppressed patients. Crit Care. 2019 May 2;23(1):152. doi: 1.1186/s13054-019-2425-6. \u003c/li\u003e\n\u003cli\u003eFerreira M, Santos M, Rodrigues J, et al. Epidemiology of bacteremia in a pediatric population - A 10-year study. \u003cem\u003eEnferm Infecc Microbiol Clin (Engl Ed)\u003c/em\u003e. Published online July 15, 2021. doi:10.1016/j.eimc.2021.06.011\u003c/li\u003e\n\u003cli\u003eAllen U, Moore D. Invasive group A streptococcal disease: Management and chemoprophylaxis. \u003cem\u003ePaediatr Child Health\u003c/em\u003e. 2010;15(5):295-302.\u003c/li\u003e\n\u003cli\u003eCole JC, Jankowski CA, Verdecia JL, Isache CL, Ravi MS, McCarter YS, Casapao AM. The Time for Action Is Now: The Impact of Timing of Infectious Disease Consultation for Staphylococcus aureus Bacteremia. Clin Infect Dis. 2023 Jun 8;76(11):2007-2009. doi: 10.1093/cid/ciad110.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Invasive Group A Streptococcus, Non-Invasive Group A Streptococcus, COVID-19, Influenza, Antibiotic stewardship ","lastPublishedDoi":"10.21203/rs.3.rs-4397131/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4397131/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003e After a decrease in pediatric invasive group A streptococcal cases during the peak of the COVID-19 infection isolation guidelines in 2020 and 2021, the Centers for Disease Control and Prevention (CDC) documented a surge in cases in multiple states across the United States during late 2022.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003e We performed a retrospective chart review exploring both invasive pediatric group A streptococcal infections (iGAS) and noninvasive group A streptococcal infections (non-iGAS) admissions to the Children\u0026rsquo;s Hospital of Georgia from July 1, 2021 to June 30, 2023. Demographics, seasonality, concomitant viral and bacterial infections, antibiotic use preferences, pediatric intensive care (PICU) admission, and mortality were included.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe found a substantial increase in both iGAS and non-iGAS cases during the study time. Most patients with iGAS presented were teenagers, white, and had sepsis and bacteremia. Non iGAS patients were not older than 11 years of age, were predominantly back, and had complicated pneumonia. Influenza was the most common concomitant virus seen in invasive and noninvasive cases, but our sample also included infections with respiratory syncytial virus (RSV), metapneumovirus (HMPV), rhinovirus and adenovirus among others. Methicillin-sensitive staphylococcus (MSSA) aureus was the most common bacteria seen in patients with both invasive and noninvasive disease. Treatment optimization was only achieved after pediatric Infectious Diseases consultation.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe surge in noninvasive and invasive pediatric GAS disease seen at our institution matched the end of COVID-19 infection masking policies in the United States. This drastic rise should be recognized, and surveillance should be reinforced. Increased knowledge and understanding of this surge in group A streptococcal infections will allow for early intervention and treatment, thereby reducing morbidity and mortality.\u003c/p\u003e","manuscriptTitle":"A Case Series of Noninvasive (non-iGAS) and Invasive (iGAS) Pediatric Group A Streptococcal Infections at a Tertiary Healthcare Center: Resurgence and Concomitant Viral Infections","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-25 19:32:51","doi":"10.21203/rs.3.rs-4397131/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ce6b15af-fd7e-45c9-84f8-a9c32cace9c1","owner":[],"postedDate":"June 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-03T05:40:12+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-25 19:32:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4397131","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4397131","identity":"rs-4397131","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}