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

Effectiveness of adjunctive clindamycin in β-lactam antibiotic-treated patients with invasive β-haemolytic streptococcal infections in US hospitals: a retrospective multicentre cohort study

Background Adjunctive clindamycin has survival benefit in invasive Group A streptococcus (GAS) infections. Like clindamycin, linezolid also leads to decreased toxin and virulence factor production. However, rising clindamycin resistance among GAS isolates and inadequate clinical data on linezolid both offer pause on which to choose. We examined the impact of adjunctive clindamycin vs. linezolid on survival among patients with GAS bloodstream infections (BSI) in the presence and absence of clindamycin resistant (clinda-R) isolates Methods Clinical characteristics, antimicrobial susceptibility testing (AST), and antibiotic therapy were examined for unique adult inpatient encounters with GAS BSIs in the PINC-AI Database. Patients treated with a β-lactam for ≥3 days ±3 days of culture who received clindamycin ±3 days of culture were overlap weighted on a propensity-score to those who received linezolid using basine patient and hospital factors. The primary outcome was odds ratio (OR) of in-hospital mortality associated with clindamycin (vs linezolid). The secondary outcome was length of stay (LOS) among survivors. Subgroups analyses were conducted excluding clindamycin receipients with clinda-R isolates (subgroup 1) and also missing clindamycin AST(including D-test; subgroup 2).Figure 1.Study Flow chart Selection of patients with Group A streptococcal blood stream infections. The database was queried for inpatients (aged ≥18 years) with blood culture displaying growth of Group A streptococcus, filtered on the basis of receiving β-lactam antibiotics within 3 days either side of culture sampling for a minimum duration of 3 days and received either adjunctive clindamycin or linezolid treatment within 3 days either side of culture sampling.Table 1:Baseline characteristics of all patients with Group A Streptococcal blood stream infections treated with β-lactam antibiotics and adjunctive clindamycin or linezolid (N=660)Abbreviations: IVIG: intravenous immunoglobulin, ICU: intensive care unit, IQR: interquartile range, SOFA: Sequential Organ Failure Assessment * This score was calculated by use of ICD-10-clinical modification codes and adapted from the methods used by Quan and colleagues ^ Calculated by use of an electronic health record-based adaption of the original Sequential Organ Failure Assessment ^^ Deteremined by clindamycin antimicrobial susceptibility and D-test results. Defined as resistant or intermediate clindamycin susceptibility results and/or a positive D-test result. † Defined as presence of ICD-10 codes coding for any of the following conditions: Human immunodeficiency virus, cancer, solid organ or hematopoietic stem cell transplantation, receipt of systemic corticosteroids, chemotherapy or other immunosuppressive therapy and immunodeficiency. ‡ Receipt of norepinephrine, epinephrine, phenylephrine, and dopamine administered within a 24-h period either side of culture sampling. Results Of 3019 β-lactam–treated inpatients with GAS BSI, 500 (17%) received clindamycin and 160 (5%) received linezolid. The prevalence of clinda-R isolates was 19%;1 isolate was linezolid resistant and excluded (Figure 1). Overlap weighting resulted in well balanced groups (Figure 2). In the overlap weighted cohort, mortality risk was similar between recipients of clindamycin (10%, [50/500]) vs linezolid (9%, [14/160]; OR 1.38 [95% CI: 0.76-2.49]). Among survivors median[interquartile range] LOS was similar between the two groups (8[9] vs. 9[8] days, p=0.45). Removing those with clinda-R isolates (N=84) and also missing AST (N=166) yielded similar results (Figure 3).Figure 2.Standardized mean differences for covariates included the propensity score calculation Standardized mean differences for covariates included in the propensity score generation averaged across exposure categories in the unweighted cohort (blue triangles) and overlap weighted cohort weight (red circles). After overlap weighting, the mean standard difference at each variable assessed was zero . Abbreviations: ICU: intensive care unit, IVIG: intravenous immunoglobulin, NSTI: necrotizing soft tissue infectionFigure 3.Odds Ratio of in-hospital mortality in patients with invasive group A streptococcal blood stream infection treated with adjunctive clindamycin versus adjunctive linezolid The ORs (95% CIs) of in-hospital mortality (including discharge to hospice) in the primary analysis and subgroup analysis with patients withclindamycin resistant isolates (subgroup 1) and those with clindamycin resistant isolates and missing clindamycin susceptibility results (subgroup 2) removed from clindamycin group. Abbreviations: CI: confidence interval Conclusion Among β-lactam-treated patients with GAS BSI, linezolid and clindamycin displayed comparable effectiveness as adjunctive antitoxin agents. Similar intrinsic effectiveness (i.e., in patients with only susceptible isolates) supports linezolid as an alternative even in low clinda-R settings. Disclosures Ahmed Babiker, MBBS, Roche: Advisor/Consultant Morgan Walker, MD, Cytovale: Advisor/Consultant

The use of clindamycin and intravenous immunoglobulin (IVIG) in treatment of invasive group A streptococcal (iGAS) infection, and the need for prophylactic antibiotics in close contacts, remains contentious. Controlled trials are unlikely to be conducted, so prospective, observational studies provide the best data to inform practice. We conducted population-based, prospective, active surveillance of iGAS infections throughout the state of Victoria, Australia (population 4.9 million), from March 2002 through August 2004. Eighty-four cases of severe iGAS infection (streptococcal toxic shock syndrome, necrotizing fasciitis, septic shock, or GAS cellulitis with shock) were identified. Clindamycin-treated patients had more severe disease than clindamycin-untreated patients but lower mortality (15% vs 39%; odds ratio [OR], 0.28; 95% confidence interval [CI], .10-.80). Among those who received concurrent IVIG, the fatality rate was lower still (7%). The adjusted point estimate of the OR for mortality was lower in clindamycin-treated patients (0.31; 95% CI, .09-1.12) and clindamycin plus IVIG-treated patients (0.12; 95% CI, .01-1.29) compared with clindamycin-untreated patients. Three confirmed cases of iGAS infection occurred in household contacts of index cases. The incidence rate of iGAS disease in contacts was 2011 (95% CI, 413-5929) times higher than the population incidence in Victoria. Our data suggest that clindamycin treatment of patients with severe iGAS infections substantially reduces mortality and that this effect may be enhanced by concurrent treatment with IVIG. The dramatically increased risk of iGAS disease among household contacts within 1 month of the index case highlights a potential role for antibiotic prophylaxis.

AimCombination treatment with clindamycin is recommended in patients with invasive group A Streptococcus infection; however, whether the same treatment is effective in invasive group B Streptococcus and S. dysgalactiae subspecies equisimilis infections remains unknown. We aimed to investigate whether clindamycin added to standard of care therapy would be effective in patients with invasive non‐group A β‐hemolytic Streptococcus infections.MethodsThis was a nationwide retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database focusing on the period between 2010 and 2018. We extracted data on patients diagnosed with sepsis due to non‐group A β‐hemolytic Streptococcus. One‐to‐four propensity score‐matching was undertaken to compare patients who were treated with clindamycin within 2 days of admission (clindamycin group) and those who did not (control group). The primary outcome was in‐hospital mortality.ResultsWe identified 3754 eligible patients during the study period. The patients were divided into the clindamycin (n = 296) and control groups (n = 3458). After one‐to‐four propensity score matching, we compared 289 and 1156 patients with and without clindamycin, respectively. In‐hospital mortality did not significantly differ between the two groups (9.7% versus 10.3%; risk difference 0.3%; 95% confidence interval, –3.5% to 4.2%).ConclusionsThis nationwide database study showed that combination therapy involving the use of clindamycin was not associated with lower in‐hospital mortality in patients with invasive non‐group A β‐hemolytic Streptococcus.

Emergency in Group A Streptococcal Infections: Single center data from Turkey.

BackgroundClindamycin suppresses invasive β-hemolytic streptococcal (iBHS) toxin production and its cidality, unlike β-lactams, is independent of bacterial inoculum. Evidence favoring the use of adjunctive clindamycin in iBHS is predominantly from in vitro and animal studies. Clinical studies, limited to single-center series or active surveillance, have yielded mixed results. Furthermore, its role in infections caused by non–group A or B β-hemolytic streptococci (NABS) remains poorly defined. Previously we were unable to demonstrate a clindamycin survival benefit in patients with group A streptococci (GAS) bacteremia. Here we examined the impact of adjunctive clindamycin on survival among patients with either invasive GAS or NABS infections from all sites.MethodsClinical characteristics, in vitro susceptibility and antibiotic therapy were examined for unique inpatient encounters with iBHS (GAS + NABS) infections in the Cerner HealthfactsTM Database. β-Lactam treated cases receiving clindamycin were matched 1:1 to non-clindamycin cases by propensity of receiving clindamycin using nearest neighbor propensity score matching with downstream adjustment using logistic regression. In-hospital mortality, length of stay (LOS) and Sequential Organ Failure (SOFA) score trajectory was compared based on the matched sample.ResultsOf 1,956 inpatients with iBHS infection treated with β-lactams at 118 hospitals between 2000 and 2015, 459 (23.5%) received adjunctive clindamycin. Propensity score matching generated 389 case-pairs with good covariate balance (Table 1, Figure 1). In-hospital mortality did not differ between matched clindamycin and non-clindamycin cases (7.2% vs. 8.0%, P = 0.66, aOR 0.88, [95% CI .49–1.57]) (Figure 2). Receipt of clindamycin early (within 24h vs. no clindamycin) also did not display a survival advantage (aOR 1.04 [0.51–2.14]). On day 4 of therapy Median SOFA score (P = 0.586) and SOFA delta (day 0–day 4) were similar between the two groups (P = 0.13; Figure 3). Amongst survivors, median [IQR] LOS was greater in the clindamycin group (8[5,12] vs. 6[4,9]; P = 0.001)ConclusionAdjunctive clindamycin was not associated with decreased mortality or degree of organ dysfunction among patients with iBHS infection already treated with β-lactams.Figure 2: Odds Ratio of In-Hospital MortalityAbbreviations: GAS: Group A Streptococcus , ICU: intensive care unit, iβHS: invasive β-Hemolytic streptococcus, NABS: Non group A β-Hemolytic streptococci , OR: odds ratioFigure 2 Legend: The figure reports the odds ratios (ORs) of in-hospital mortality and 95% confidence intervals in the unmatched and unadjusted analysis, matched and unadjusted analysis, and primary analysis of all propensity-matched pairs with downstream adjustment with logistic regression for proven ißHS, vasopressor use and ICU (within 24h of culture sampling), as well as sensitivity analyses on propensity matched pairs of 2:1 match and subgroup analysis on propensity matched pairs of (1) proven ißHS alone (2) probable ißHS alone (3) ICU admission (within 24h of culture sampling) (4) patients receiving vasopressor therapy (within 24h of culture sampling) (5) Group A ißHS alone (6) Non Group A ißHS alone. There was no statistically significant difference in the ORs for in-hospital mortality between clindamycin and propensity-matched non-clindamycin cases in the primary analysis (*) as well as all sensitivity and subgroup (†) analyses.Figure 3: SOFA Score Trajectory by Survival StatusAbbreviations: B: Non-Clindamycin cases, BC: Clindamycin CasesFigure 3 Legend: SOFA score by day of therapy of clindamycin and non-clindamycin matched cases based on survival status from day zero (day prior to antibiotic therapy) to day four of therapy. The linear mixed models were used to assess the time trends and the clindamycin effect on the longitudinal SOFA scores. SOFA trajectory was examined for the post matching sample. Square root transformation was applied to the SOFA score to meet the normality assumption Mean Baseline SOFA scores prior to therapy were similar amongst clindamycin and non-clindamycin subjects (mean [standard deviation(SD)] SOFA score: 1.88[2.48] vs. 1.96[2.60]; p= 0.634). On day 4 of therapy SOFA scores were similar between remaining 310 clindamycin and 286 non-clindamycin hospitalized patients (mean[SD] SOFA score: 1.79[2.88] vs. 1.67 [2.49]; p=0.586). The SOFA delta (day 0 SOFA score - day 4 SOFA score) was similar between the two groups (p=0.1331). When examined amongst survivors only, SOFA scores on day 4 of therapy were similar between and 272 non-clindamycin and 310 clindamycin hospitalized patients (mean[SD] SOFA score: 1.45 [2.20] vs. 1.52 [2.44])This work was funded in part by the Intramural Research Program of the National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Diseases.The opinions expressed in this abstract are those of the authors and do not represent any position or policy of the National Institutes of Health, the United States Department of Health and Human Services, or the United States government.DisclosuresAll authors: No reported disclosures.

The incidence of invasive group A streptococcus (iGAS) infections varies in time and geographically for unknown reasons. We performed a nationwide survey to assess the population-based incidence rates and outcomes of children with iGAS infections. We collected data on patients from hospital discharge registries and the electronic databases of microbiological laboratories in Finland for the period 1996-2010. We then recorded the emm types or serotypes of the strains. The study physician visited all university clinics and collected the clinical data using the same data entry sheet. We identified 151 children with iGAS infection. Varicella preceded iGAS infection in 20% of cases and fasciitis infection in 83% of cases. The annual incidence rate of iGAS infection was 0.93 per 100,000 in 1996-2000, 1.80 in 2001-2005 and 2.50 in 2006-2010. The proportion of emm 1.0 or T1M1 strains peaked in 1996-2000 and again in 2006-2010, to 44% and 37% of all typed isolates. The main clinical diagnoses of the patients were severe soft-tissue infection (46%), sepsis (28%), empyema (10%), osteoarticular infection (9%) and primary peritonitis (5%). Severe pain was the most typical symptom for soft-tissue infections. More than half of the patients underwent surgery and received clindamycin. The readmission rate was 7%, and the case fatality rate was 2%. The incidence rate of pediatric iGAS infections tripled during our study. The increase was not, however, the result of a change in the strain types causing iGAS. Varicella immunization would likely have prevented a significant number of the cases.

BackgroundGroup A Streptococcus is responsible for severe and potentially lethal invasive conditions requiring intensive care unit (ICU) admission, such as streptococcal toxic shock-like syndrome (STSS). A rebound of invasive group A streptococcal (iGAS) infection after COVID-19-associated barrier measures has been observed in children. Several intensivists of French adult ICUs have reported similar bedside impressions without objective data. We aimed to compare the incidence of iGAS infection before and after the COVID-19 pandemic, describe iGAS patients’ characteristics, and determine ICU mortality associated factors.MethodsWe performed a retrospective multicenter cohort study in 37 French ICUs, including all patients admitted for iGAS infections for two periods: two years before period (October 2018 to March 2019 and October 2019 to March 2020) and a one-year after period (October 2022 to March 2023) COVID-19 pandemic. iGAS infection was defined by Group A Streptococcus isolation from a normally sterile site. iGAS infections were identified using the International Classification of Diseases and confirmed with each center's microbiology laboratory databases. The incidence of iGAS infections was expressed in case rate.ResultsTwo hundred and twenty-two patients were admitted to ICU for iGAS infections: 73 before and 149 after COVID-19 pandemic. Their case rate during the period before and after COVID-19 pandemic was 205 and 949/100,000 ICU admissions, respectively (p < 0.001), with more frequent STSS after the COVID-19 pandemic (61% vs. 45%, p = 0.015). iGAS patients (n = 222) had a median SOFA score of 8 (5–13), invasive mechanical ventilation and norepinephrine in 61% and 74% of patients. ICU mortality in iGAS patients was 19% (14% before and 22% after COVID-19 pandemic; p = 0.135). In multivariate analysis, invasive mechanical ventilation (OR = 6.08 (1.71–21.60), p = 0.005), STSS (OR = 5.75 (1.71–19.22), p = 0.005), acute kidney injury (OR = 4.85 (1.05–22.42), p = 0.043), immunosuppression (OR = 4.02 (1.03–15.59), p = 0.044), and diabetes (OR = 3.92 (1.42–10.79), p = 0.008) were significantly associated with ICU mortality.ConclusionThe incidence of iGAS infections requiring ICU admission increased by 4 to 5 after the COVID-19 pandemic. After the COVID-19 pandemic, the rate of STSS was higher, with no significant increase in ICU mortality rate.

Streptococcus is one of the common pathogens of suppurative infections. Invasive group A Streptococcus (iGAS) infections often develop from skin or soft tissue infections, and streptococcal toxic shock syndrome is considered the main cause of death in Chinese children with iGAS infectious disease. However, soft tissue infections caused by iGAS infections, especially the formation of abscesses, are relatively rare. A retrospective study was conducted, and pediatric in-patients who were diagnosed with an iGAS infection identified by cultures from normally sterile sites and treated in a tertiary hospital during 2016-2018 were included. A total of 14 patients were identified, which included 10 boys and four girls. The patients had an age range from 3 months to 10 years and were diagnosed with soft tissue infections and a formation of abscesses caused by iGAS infections. The most common sites of infections were the lower limbs. In five patients, the abscess was accompanied by fever, and the local soft tissue showed redness, swelling, tenderness, and an elevated skin temperature. Laboratory findings included an increased white blood cell (WBC) count in 12 patients, an increased C reactive protein (CRP) level in seven patients, and an increased erythrocyte sedimentation rate (ESR) in 10 patients. No patients had an elevated procalcitonin level. For all 14 patients, we performed puncture and drainage of abscesses, and cultured GAS from the drainage fluid. All children also received antibiotic treatment. During 2 months of follow-up, the patients' condition remained stable and no evidence of kidney or heart damage was observed. For pediatric patients with abscesses, early diagnosis, prompt treatment with incision and drainage, and immediate culture of the drainage fluid are important. Upon confirmation of an iGAS infection, β-lactam antibiotics should be given to provide effective treatment, and in some patients with poor therapeutic outcomes, the use of vancomycin as an alternative can achieve the desired results.

Clinical and microbiological characterization of invasive group a Streptococcus infection in children in Japan: A single-center experience

Adjunctive linezolid versus clindamycin for toxin inhibition in β-lactam-treated patients with invasive group A streptococcal infections in 195 US hospitals from 2016 to 2021: a retrospective cohort study with target trial emulation

To the Editors: During the second and third year of the COVID pandemic, an increased number of serious cases due to different microorganisms have been reported. In the second half of 2022, it has been reported that there has been an increase in invasive group A streptococcal (iGAS) infections in many countries including England, the Netherlands and others.1–3 iGAS is defined as a life-threatening invasive infection characterized by the isolation of Streptococcus pyogenes from normally sterile body fluids with culture or by pathogen-specific polymerase chain reaction (PCR). If GAS has grown from a probable carrier location, such as the throat, and the clinical course is compatible with GAS disease and no other causing organism has been found, these patients need to be handled as iGAS.4 Before the pandemic, GAS was the most common pathogen among children in Europe who had to be hospitalized for a community-acquired bacterial infection. Patients with GAS infection had a 12% impairment at discharge and a 2% fatality rate. Increases in toxic shock syndrome, necrotizing fasciitis and pleural empyema have all been linked to increased mortality.4 In UK, during the last couple of months, the rate per 100,000 population of iGAS is higher among children.1 Between December 2022 and January 2023, in our tertiary care facility, we followed up 7 consecutive cases of iGAS infection—3 boys and 4 girls, ages 37–96 months—without any relation to one another (Table 1). All children were previously healthy. Five children were admitted to the pediatric intensive care unit, including 1 with toxic shock syndrome and 4 with pleural effusion/empyema. In 6 out of 7 children, the diagnosis of iGAS infection was made based on a positive culture and/or PCR from a typically sterile place, with the pleural fluid being the most frequent site. iGAS infection was defined in a child with toxic shock syndrome based on positive throat culture. In Table 1, antibiotic therapy is displayed. Each patient received clindamycin and 1 patient received intravenous immunoglobulin (IVIG). Due to empyema, thoracic tubes had to be inserted in 5 patients. In 2 of the pleural empyema cases, tube thoracostomy was carried out; in the third video assisted thoracostomy and in the fourth, thoracotomy and decortication were carried out. One child with GAS bacteremia required surgery for mastoiditis, and throughout the course of the investigation, sinus venous thrombosis was detected. Five children required pediatric intensive care unit stay. The length of hospital stay ranged from 7 to 21 days. TABLE 1. - Clinical Characteristics of 7 Children with Invasive Group A Streptococcal Infection Patient Age (month) Gender Diagnosis Culture Multiplex PCR Treatment PICU Stay Length of hospital stay (day) 1 37 Girl Pleural Empyema - Pleural fluid Streptococcus pyogenes Meropenem + vancomycin + clindamycin IVIG Thoracotomy and decortication + 14 2 40 Girl Pleural Empyema Throat Streptococcus pyogenes Pleural fluid Streptococcus pyogenes Tube thoracostomy Ceftriaxone + clindamycin + 9 3 96 Girl Pleural Empyema - Pleural fluid Streptococcus pyogenes Meropenem + vancomycin + clindamycin Tube thoracostomy Video assisted thoracostomy + 15 4 62 Boy Bacteremia, Mastoiditis, Sinus vein thrombosis Blood Streptococcus pyogenes - Meropenem + vancomycin + clindamycin Mastoidectomy - 21 5 48 Boy Pleural Empyema - Pleural fluid Streptococcus pyogenes Ceftriaxone + vancomycin + clindamycin Tube thoracostomy + 10 6 59 Boy Toxic Shock Syndrome Throat Streptococcus pyogenes - Ceftriaxone + vancomycin + clindamycin + 7 7 42 Girl Bacteremia, Pleural Empyema Blood Streptococcus pyogenes - Ceftriaxone + clindamycin - 10 IVIG, intravenous immune globulin; PICU, pediatric intensive care unit. Both the frequency and morbidity of iGAS infections increased after the COVID-19 pandemic as before. While there was only one iGAS case during the previous 3 years, 7 patients in a row were hospitalized during a 2-month period in our setting. Clindamycin would be efficient to deactivate M-protein and these exotoxins because S. pyogenes has the cell wall M-protein that prevents complement activation and reduces phagocytosis. This would produce a positive outcome similar to our case series.4,5 Although culture is the gold standard method for diagnosis, molecular methods such as multiplex PCR are important in identifying the causative agent. Despite treatment, we have seen serious complications in our case series, such as pleural decortication, mastoiditis, sinus venous thrombosis and toxic shock syndrome. Early diagnosis of patients (using molecular techniques included) and the initiation of appropriate treatment including clindamycin, are crucial. To comprehend the postpandemic condition, it is essential to monitor the clinical findings and prognosis of iGAS cases from various countries.

Reported outbreaks of invasive group A Streptococcus (iGAS) infections among people who inject drugs (PWID) and people experiencing homelessness (PEH) have increased, concurrent with rising US iGAS rates. We describe epidemiology among iGAS patients with these risk factors. We analyzed iGAS infections from population-based Active Bacterial Core surveillance (ABCs) at 10 US sites from 2010 to 2017. Cases were defined as GAS isolated from a normally sterile site or from a wound in patients with necrotizing fasciitis or streptococcal toxic shock syndrome. GAS isolates were emm typed. We categorized iGAS patients into four categories: injection drug use (IDU) only, homelessness only, both, and neither. We calculated annual change in prevalence of these risk factors using log binomial regression models. We estimated national iGAS infection rates among PWID and PEH. We identified 12 386 iGAS cases; IDU, homelessness, or both were documented in ~13%. Skin infections and acute skin breakdown were common among iGAS patients with documented IDU or homelessness. Endocarditis was 10-fold more frequent among iGAS patients with documented IDU only versus those with neither risk factor. Average percentage yearly increase in prevalence of IDU and homelessness among iGAS patients was 17.5% and 20.0%, respectively. iGAS infection rates among people with documented IDU or homelessness were ~14-fold and 17- to 80-fold higher, respectively, than among people without those risks. IDU and homelessness likely contribute to increases in US incidence of iGAS infections. Improving management of skin breakdown and early recognition of skin infection could prevent iGAS infections in these patients.

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.

Background In December 2022 the CDC issued an alert about possible increase of invasive group A Streptococcus infections (iGAS) among children in the United States. Colorado and Minnesota observed an increase in the number of cases in the Fall 2022. Similarly, the Pennsylvania Department of Health issued a health alert that was then lifted in February 2023. Preliminary CDC data showed that iGAS infections were higher in some areas of the country compared to pre-pandemic levels. Lehigh Valley Reilly Children’s Hospital is a community teaching hospital in Allentown, Pennsylvania. A rise in the number of children admitted with GAS infections was noted in the same period compared to previous years. The aim of our study was to determine the clinical characteristics of patients admitted with iGAS and non-iGAS infections during fall and winter 2022-2023. Methods Retrospective chart review of patients 18 years and younger admitted to Reilly Children’s Hospital between September 1st 2022 through March 31st 2023 and diagnosed with GAS infection plus those admitted with the same diagnosis between 2018 and 2022. Results There were 19 children admitted to the hospital with GAS infection: 6 (32%) with iGAS and 13 (68 %) with non-iGAS infections. The iGAS infections included bacteremia without source (2), myositis (1), pneumonia (2), and vascular infection (1). Non-iGAS infections included retropharyngeal abscess (3), peritonsillar abscess (2), parotid abscess (1), submandibular abscess (1), lymphadenitis (2), mastoiditis (1), cellulitis (1), pharyngitis (1), and erythema nodosum (1). Six children required intensive care and two were transferred to higher level care. Median age was 2.2 year for iGAS infections and 4.8 years for non-iGAS. All but one patient had no underlying medical conditions. There were no patient deaths. In 2018 there were zero cases of iGAS infection; in 2019: two cases; 2020: two cases; 2021: zero cases. There were no admissions between May 2020 and April 2022 for either iGAS or non-iGAS. Conclusion The number of children admitted for iGAS and non-iGAS infections in the fall and winter of 2022-2023 surpassed the preceding 4 years combined. This is reflective of what was happening in some other areas of the country as a result of reduced exposure and lack of immunity due to pandemic restrictions. Disclosures All Authors: No reported disclosures