Effectiveness of clindamycin and intravenous immunoglobulin, and risk of disease in contacts, in invasive group a streptococcal infections.

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.

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

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

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.

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.

To the Editor: Group A streptococci (GAS) can cause severe invasive diseases, such as necrotizing fasciitis, streptococcal toxic shock syndrome, and sepsis. In 2012, ≈11,000 cases of invasive GAS (iGAS) disease and 1,100 associated deaths occurred in the United States (1,2). The risk for iGAS infection is 10 times higher among Native Americans than among the general population (3). Other predisposing factors for iGAS infection include skin wounds and underlying diseases, such as diabetes (1,3,4). Household risk factors include exposure to children with pharyngitis and crowding (4). Most iGAS infections occur sporadically within the community. Postpartum and postsurgical clusters arising from a common nosocomial source occur but are rare (5). During the winter of 2012–13, a 3-fold increase in necrotizing fasciitis was observed at an Arizona hospital (hospital X) that predominantly treats Native Americans. Tribal leadership initiated a collaborative investigation with state and federal officials to characterize the outbreak and implement appropriate control measures. A confirmed case of iGAS was defined as isolation of GAS from normally sterile sites (i.e., blood) or isolation of GAS from nonsterile sites (i.e., wound) in the presence of necrotizing fasciitis or streptococcal toxic shock syndrome among patients who sought care at hospital X during August 2012–March 2013. Hospital X serves ≈45,000 persons in a rural community. Eleven confirmed iGAS cases were identified (Figure), of which 8 (73%) occurred in women and 3 (27%) occurred in men. The case-patients had a mean age of 63 years (range 32–92 years). All cases were community-onset illnesses; none of the case-patients had recent exposures to health care settings, and all were of Native American ancestry. Of the 11 case-patients, 8 required critical care treatment and 3 died. Nine (82%) case-patients had open wounds or skin breakdown (e.g., skin abrasion, burns), and 9 had underlying medical conditions that are known risk factors for iGAS (e.g., obesity, diabetes, chronic kidney or heart disease, alcoholism). Figure Week of symptom onset and principal clinical syndrome of patients with confirmed invasive group A streptococcus infections at hospital X, Arizona, August 2012–March 2013. STSS, streptococcal toxic shock syndrome. Five GAS isolates were available. Two of the isolates were emm type 11; antimicrobial drug–susceptibility profiles for the 2 were identical (i.e., tetracycline resistant). The 2 patients reported no close contact with each other, but they had the same home health aide. The other 3 isolates had different emm types (1, 12, and 82) and were antimicrobial drug pansensitive. We interviewed 58 household contacts of the case-patients (35 adults, 23 children) regarding symptoms and risks for secondary GAS infection. Among these contacts, 2 adults reported a sore throat and 6 children reported fever (without sore throat), but no confirmed secondary GAS infections were identified. Because of the known increased risk for iGAS among Native Americans and the level of crowding (average of 2–3 persons/bedroom) and the high proportion of adult household contacts with predisposing underlying conditions (29%) in this population, azithromycin prophylaxis was offered to household contacts who spent >24 hours with a case-patient during the 7 days preceding the onset of illness. With the exception of the 2 case-patients with a common health aide, we found no common epidemiologic links or common behaviors among patients that suggested a single-source outbreak. This was further supported by the finding of multiple emm types among the isolates. These are not unusual findings in community outbreaks of iGAS; clusters of iGAS cases have often been observed without a common source (6–8). Localized and transient increases in sporadic GAS infections may occur because of an influx of a new emm type into a population with low levels of community immunity to that specific emm type; an increase in the detection and reporting of iGAS without a true increase in infection; or an increase in conditions that predispose persons to iGAS, such as GAS pharyngitis among children or concurrent influenza or other virus outbreaks in the community. Past studies have shown that the risk of secondary iGAS infection among household contacts of patients with iGAS disease is higher than that among the general population but still low (5). Although Centers for Disease Control and Prevention guidelines do not recommend routine chemoprophylaxis for household contacts of patients with iGAS infection, the guidelines state that providers may choose to offer antimicrobial drug prophylaxis to those household contacts at increased risk for iGAS infection (5). Because Native Americans have increased rates of iGAS disease, compared with those of the general population, and because households in this investigation were crowded and many contacts had predisposing underlying conditions, we recommended that household contacts receive prophylaxis if given within 30 days of the index case-patient’s illness (5). No additional cases were reported at least 3 months after the investigation and intervention.

Cardiac rupture and toxic shock syndrome by invasive group a Streptococcus in a Fontan patient with Asplenia syndrome

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

Current scenario of recently rising up cases of invasive group A streptococcal (iGAS) infections in younger children in many European nations: clinical management and prospective counteracting measures – an update

Invasive group A streptococcal infections as a consequence of coexisting or previous viral infection in the post-COVID-19 pandemic period.

Invasive group A streptococcal infections in children and adolescents in Denmark during 2022–23 compared with 2016–17 to 2021–22: a nationwide, multicentre, population-based cohort study

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

PurposeThe incidence of invasive Group A Streptococcus (iGAS) infection and streptococcal toxic shock syndrome (STSS) is increasing. Early detection and diagnosis of cases that may progress to STSS are currently difficult. In this study, we aimed to identify biomarkers and emm type, one of the virulence factors, associated with STSS development.MethodsIn this multicentre observational study including patients with iGAS infection (n = 305), we investigated the relative associations of host factors, clinical manifestations, biomarkers, and emm type with STSS.ResultsThe overall mortality rate was 15.4%; the fatality rate within 28 days of admission was higher in patients with STSS (67.9%, 38/56) than in those without (3.6%, 9/249). The most predominant type was emm1 (38%), detected in 73.2% of the patients with STSS. Risk factors for STSS identified by multivariable analysis included underlying kidney disease (odds ratio [OR], 10.7; 95% confidence interval [CI], 2.1–54.0, p = 0.004), bacteraemia without primary focus (OR, 3.6; 95% CI 1.2–11.1, p = 0.023), necrotizing fasciitis (OR, 8.7; 95% CI 2.6–29.4, p < 0.001), white blood cell count (WBC) < 4,000/µL (OR, 7.8; 95% CI 2.4–25.6, p = 0.001), serum creatine kinase (CK) ≥ 300 U/L (OR, 7.5; 95% CI 2.8–19.8, p < 0.001), and emm1 (OR, 5.2; 95% CI 2.0–13.4, p = 0.001).ConclusionWBC < 4,000/µL and CK level ≥ 300 U/L on admission are additional relevant biomarkers for STSS prediction. The most predominant iGAS type, emm1, was significantly associated with STSS.

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