Version July 2025
INTRODUCTION —
Group A Streptococcus (GAS; Streptococcus pyogenes) is an aerobic gram-positive coccus that causes a broad array of infections. GAS is most commonly associated with pharyngitis or skin and soft tissue (non-necrotizing) infection; these are not typically associated with invasive infection.
Less commonly, GAS causes invasive disease, which can include any of the following:
●GAS bacteremia
●Toxic shock syndrome (TSS)
●Necrotizing soft tissue infection
●Bone or joint infection
●Pneumonia or empyema
This topic will review the epidemiology, clinical manifestations, treatment, and prognosis of invasive GAS infection in children. Related topics include:
●TSS (see "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis" and "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention")
●Necrotizing soft tissue infections (see "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention" and "Necrotizing soft tissue infections" and "Surgical management of necrotizing soft tissue infections")
●Osteomyelitis (see "Hematogenous osteomyelitis in children: Evaluation and diagnosis" and "Hematogenous osteomyelitis in children: Management")
●Bacterial arthritis (see "Bacterial arthritis: Epidemiology, pathogenesis, and microbiology in infants and children" and "Bacterial arthritis: Clinical features and diagnosis in infants and children" and "Bacterial arthritis in infants and children: Treatment and outcome")
●Pneumonia and empyema (see "Pneumonia in children: Epidemiology, pathogenesis, and etiology" and "Community-acquired pneumonia in children: Clinical features and diagnosis" and "Epidemiology, clinical presentation, and evaluation of parapneumonic effusion and empyema in children" and "Management and prognosis of parapneumonic effusion and empyema in children")
INCIDENCE —
GAS bacteremia usually occurs secondary to a primary site of infection, most commonly in the skin and soft tissues [1,2]. The estimated incidence of GAS bacteremia and/or invasive infection in children is 1 to 3 cases per 100,000 per year [2-5]. The incidence is greatest in children ≤2 years (approximately 4 to 5 cases per 100,000) [2,5].
Among hospitalized patients, invasive GAS infection accounts for approximately 0.3 to 0.9 percent of pediatric hospital admissions [6,7].
In the United States, invasive GAS attack rates have been relatively stable since the mid-1990s, with approximately 100 to 200 pediatric cases reported to the Active Bacterial Core (ABC) surveillance at the Centers for Disease Control and Prevention (CDC) each year [5]. There were fewer cases reported in 2020 and 2021, likely due to the impact of social distancing and other infection control measures during the height of the coronavirus disease 2019 (COVID-19) pandemic [2,8]. There was then a spike in reported cases in the fall and winter of 2022 in the United States, Canada, and Europe [9-11].
However, by 2023 and 2024, rates of invasive GAS infection appear have returned to levels similar to those seen in prepandemic years [5,12].
MICROBIOLOGY —
Certain strains of GAS may be more likely to cause invasive infection. A small number of M-types of GAS (1, 4, 12) are responsible for >50 percent of invasive infections [2]. In addition, GAS strains isolated from invasive cases produce a toxin called NADase [13]. (See "Group A streptococcus: Virulence factors and pathogenic mechanisms", section on 'Virulence factors' and "Group A streptococcus: Virulence factors and pathogenic mechanisms", section on 'Toxins and other secreted virulence factors'.)
PREDISPOSING FACTORS —
The following predisposing factors are associated with invasive GAS infection:
●Varicella-zoster virus (VZV) – Prior to widespread use of the VZV vaccine, approximately 15 to 30 percent of cases of GAS bacteremia and/or invasive GAS infection were associated with VZV infection [14-24]. Fever on or beyond the fourth day of the exanthem in children with VZV should prompt consideration of GAS bacteremia [25]. (See "Clinical features of varicella-zoster virus infection: Chickenpox".)
VZV vaccination appears to prevent VZV-associated GAS infection; however, whether this has had an impact on the overall rate of invasive GAS disease is uncertain. One report from a tertiary center in the United States found that while the percentage of VZV-related GAS hospitalizations declined from 27 to 2 percent before and after widespread use of the varicella vaccine, the overall annual hospitalization rate for invasive GAS infection did not change [16]. Another study from Israel found that the overall annual rate of pediatric invasive GAS infections fell by nearly 50 percent (from 2.4 to 1.3 cases per 100,000) after introduction of the varicella vaccine [26]. (See "Vaccination for the prevention of chickenpox (primary varicella infection)".)
●Influenza infection – GAS is a common cause of secondary bacterial infection in children with influenza and contributes to influenza-related morbidity and mortality [27,28]. (See "Seasonal influenza in children: Clinical features and diagnosis".)
●Trauma, burns, and surgery – Approximately 30 to 40 percent of invasive GAS infections are associated with recent skin disruption from minor trauma (eg, cuts, abrasions, body piercing), burns, eczema, and/or recent surgery [14-16]. (See "Burn wound infection and sepsis".)
●Immunosuppression or immunodeficiency – Invasive GAS infections commonly occur in children with underlying immunocompromised conditions including HIV, nephrotic syndrome, solid organ transplant, primary immune disorders, autoimmune disorders, and chronic immunosuppressive medication use [1,29].
●Malignant neoplasm – Underlying malignancy has been noted in 5 to 10 percent of patients with invasive GAS infection [14-17].
●Age <2 years – The risk of invasive GAS infection is highest in infants under the age of two years [14,15,30,31]. In neonates, GAS infection can occur as a result of vertical transmission from the mother or from nosocomial acquisition from medical personnel [32].
●Intravenous drug use – Intravenous drug use is a risk factor for invasive GAS infection in adolescents and adults [33-39]. (See "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis".)
SOURCES OF BACTEREMIA —
GAS bacteremia may arise in patients with infections of the skin, soft tissues, pharynx, and lungs.
Skin infection — The most frequent source of GAS bacteremia in children is the skin [25]. Cellulitis, minor trauma, burns, and varicella-zoster virus (VZV) infection are the most commonly associated predisposing conditions. Affected patients may have other signs of invasive GAS infection, such as osteomyelitis, septic arthritis, necrotizing fasciitis, or myonecrosis [33]. (See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis" and "Burn wound infection and sepsis" and "Necrotizing soft tissue infections".)
Pharyngitis and respiratory tract — Bacteremia associated with GAS pharyngitis is an uncommon occurrence; even with scarlet fever, it occurs in only 0.3 percent of febrile patients [40]. Nevertheless, among patients with scarlet fever, the pharynx is the most common source of bloodstream GAS. (See "Group A streptococcal tonsillopharyngitis in children and adolescents: Clinical features and diagnosis".)
Bacteremic children infrequently have additional complications such as extension of infection into the sinuses, peritonsillar tissue, or mastoids (septic scarlet fever or scarlet fever anginosa).
The least common source of bacteremia in children has been the lower respiratory tract. When bacteremic GAS pneumonia occurs, it usually is associated with prior viral infections, particularly influenza, which is associated with increased mortality risk [41,42].
CLINICAL MANIFESTATIONS —
The clinical manifestations of GAS bacteremia include those of the primary site of infection and of the bacteremia. High fever (>39°C [102.2°F]), elevated white blood cell count, and elevated erythrocyte sedimentation rate (ESR) are typical but nonspecific findings [1,23,43]. A scarlatiniform rash (picture 1 and picture 2) followed by desquamation is often noted.
A focal source of infection is present in 60 to 90 percent of cases and may include the following [1-3,14-17,44-47]:
●Cellulitis (15 to 35 percent)
●Lymphadenitis (5 to 17 percent)
●Abscess (5 to 19 percent)
●Septic arthritis (7 to 15 percent)
●Pyomyositis/myositis (12 percent)
●Osteomyelitis (5 to 12 percent)
●Pneumonia/empyema (5 to 15 percent)
●Necrotizing fasciitis (1 to 9 percent)
●Peritonitis (1 to 5 percent)
●Thrombophlebitis (0.5 to 5 percent)
●Meningitis or epidural abscess (1 to 4 percent)
●Pericarditis (1 to 3 percent)
Patients without a focal source of infection tend to have a less severe disease course [17].
The clinical course may be fulminant, and severe organ dysfunction can occur, including [1,3,14,17,44]:
●Disseminated intravascular coagulation (10 to 20 percent)
●Hepatic dysfunction (17 percent)
●Toxic shock syndrome (5 to 15 percent)
●Hypotension (10 to 15 percent)
●Respiratory failure (10 to 15 percent)
●Kidney failure (5 percent)
Bacteremia associated with the early onset of shock and organ failure is characteristic of the case definition of streptococcal toxic shock syndrome (table 1). Affected patients typically develop kidney failure, acute respiratory distress syndrome, hepatic dysfunction, and a diffuse capillary leak syndrome. (See "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis".)
Patients with GAS bacteremia also can develop secondary infections. Musculoskeletal infections are the most common focal infections resulting from the bacteremia. In one case series, 12 of 29 patients with acute hematogenous osteomyelitis caused by GAS had a positive blood culture [45].
TREATMENT
Supportive care — Supportive care for patients with invasive GAS infections may include:
●Intravenous fluid therapy (see "Shock in children in resource-abundant settings: Initial management", section on 'Fluid resuscitation' and "Maintenance intravenous fluid therapy in children")
●Hemodynamic support for patients with evidence of shock (see "Children with sepsis in resource-abundant settings: Rapid recognition and initial resuscitation (first hour)", section on 'Hypotensive patients')
●Respiratory support for patients with respiratory compromise (see "Continuous oxygen delivery systems for the acute care of infants, children, and adults" and "High-flow nasal cannula oxygen therapy in children")
●Fever control
Consultation with appropriate specialists (including infectious disease specialists, surgeons, and pediatric intensivists) should occur early in the disease course.
Antibiotic therapy — Antibiotic therapy should be tailored to antibiotic susceptibilities.
Choice of regimen — The approach to treatment of invasive GAS infection should be guided by the primary presentation, as detailed in separate topics:
●Toxic shock syndrome (TSS) (see "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'Antibiotic regimens')
●Necrotizing soft tissue infection (see "Necrotizing soft tissue infections", section on 'Antibiotic therapy')
●Bone and joint infections (see "Hematogenous osteomyelitis in children: Management", section on 'Antimicrobial therapy' and "Bacterial arthritis in infants and children: Treatment and outcome", section on 'Antibiotic therapy')
●Pneumonia and empyema (see "Pneumonia in children: Inpatient treatment", section on 'Empiric therapy' and "Management and prognosis of parapneumonic effusion and empyema in children", section on 'Antibiotic therapy')
For GAS bacteremia in the absence of shock, organ failure, or necrotizing infection, we suggest initial combination therapy with both:
●A beta-lactam (eg, penicillin G 200,000 to 400,000 units/kg per day intravenously [IV], divided every 4 to 6 hours in patients with normal kidney function; maximum daily dose of 24 million units), plus
●Clindamycin (25 to 40 mg/kg per day IV, divided every 6 to 8 hours; maximum daily dose of 2.7 grams)
GAS is exquisitely susceptible to beta-lactam antibiotics. The rationale for adding clindamycin is that it suppresses toxin production and may reduce the risk of treatment failure. This approach is based on observational clinical studies and animal data [48-50]. Clindamycin should not be used as a monotherapy for invasive GAS infection, because it is not bactericidal and because the prevalence of clindamycin resistance among GAS isolates has been rapidly increasing since the early 2000s in many regions [51-53]. In the Center for Disease Control and Prevention (CDC) ABCs surveillance report from 2022, one-third of all invasive GAS isolates were resistant to clindamycin [30].
Because of the high prevalence of clindamycin resistance, some experts suggest linezolid rather than clindamycin in the treatment regimen for invasive GAS infection, though there are few data to support this approach [54]. Local antibiotic susceptibility patterns should be used to guide the selection of clindamycin versus linezolid for empiric treatment of these infections.
Duration of therapy — Patients with GAS bacteremia are treated for a minimum of 14 days. However, in patients with serious soft tissue infection (eg, necrotizing fasciitis), length of therapy depends upon the clinical response of the soft tissue infection to antibiotic treatment. Therapy is usually continued for 14 days from the last positive culture obtained during surgical debridement. There are no clinical studies addressing the optimal duration of antibiotic therapy in GAS bacteremia, and duration of antibiotic therapy should be individualized.
How long combination agents should be used is unknown. For children without necrotizing fasciitis who are initially treated with combination penicillin and clindamycin, we suggest that clindamycin can be discontinued once the child is afebrile, clinically well, and without evidence of shock or other manifestations of toxic shock syndrome.
Surgical consultation — If there is a focal site of infection (eg, necrotizing soft tissue infection, osteomyelitis, septic arthritis, empyema), appropriate surgical specialists should be consulted to determine whether the patient requires surgical exploration, drainage, and/or resection of necrotic tissue. (See "Surgical management of necrotizing soft tissue infections" and "Hematogenous osteomyelitis in children: Management", section on 'Indications for surgery' and "Bacterial arthritis in infants and children: Treatment and outcome", section on 'Drainage' and "Management and prognosis of parapneumonic effusion and empyema in children", section on 'Surgical therapy'.)
Adjunctive intravenous immune globulin (IVIG) — IVIG is suggested for patients with severe invasive GAS infections, particularly TSS and necrotizing soft tissue infection [55]. This is discussed separately. (See "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'Intravenous immune globulin' and "Necrotizing soft tissue infections", section on 'Intravenous immune globulin'.)
PROGNOSIS —
Invasive GAS disease is a serious infection. The estimated mortality rate associated with invasive GAS infections in children ranges from 2 to 8 percent [1,3,4,14,17,22,43,44]. Long-term disability occurs in an additional 3 to 8 percent of children following invasive GAS infection [1,17].
Mortality rates vary depending on the clinical syndrome. In a report of 1272 pediatric cases of invasive GAS disease, case fatality rates according to the type of clinical syndrome were as follows [2]:
●Septic shock – 10 percent
●Meningitis – 9 percent
●Toxic shock syndrome – 5 percent
●Bacteremia without an apparent focus – 5 percent
●Abdominal/peritoneal infection – 5 percent
●Necrotizing fasciitis – 4 percent
●Pneumonia – 2 percent
●Osteomyelitis – 1 percent
●Septic arthritis – No deaths
●Cellulitis or abscess with associated bacteremia – No deaths
SUMMARY AND RECOMMENDATIONS
●Incidence – GAS bacteremia usually occurs secondary to a primary site of infection, most commonly in the skin and soft tissues. The estimated incidence of invasive GAS infection in children is 2 to 3 cases per 100,000 per year. The highest incidence is in infants ≤1 year of age. (See 'Incidence' above.)
●Predisposing factors – Predisposing factors that increase the risk of invasive GAS infection include (see 'Predisposing factors' above):
•Influenza infection
•Varicella-zoster infection
•Preceding skin disruption from minor trauma, burns, eczema, or recent surgery
•Age <1 year
•Underlying immunocompromise
•Malignancy
•Intravenous drug use
●Clinical manifestations – The clinical manifestations of GAS bacteremia include those of the primary site of infection and signs and symptoms attributable to bacteremia. High fever, elevated white blood cell count, and elevated erythrocyte sedimentation rate (ESR) are common but nonspecific. The clinical course may be fulminant, and severe organ dysfunction can occur. Among patients with focal infections, skin and soft tissue infections are the most common sites. Patients without a focal source of infection tend to have less severe disease. (See 'Clinical manifestations' above.)
●Management
•Antibiotic therapy – The approach to treatment of invasive GAS infection should be guided by the antibiotic susceptibilities and the primary presentation, as detailed in separate topics:
-Toxic shock syndrome (TSS) (see "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'Antibiotic regimens')
-Necrotizing soft tissue infection (see "Necrotizing soft tissue infections", section on 'Antibiotic therapy')
-Bone and joint infections (see "Hematogenous osteomyelitis in children: Management", section on 'Antimicrobial therapy' and "Bacterial arthritis in infants and children: Treatment and outcome", section on 'Antibiotic therapy')
-Pneumonia and empyema (see "Pneumonia in children: Inpatient treatment", section on 'Empiric therapy' and "Management and prognosis of parapneumonic effusion and empyema in children", section on 'Antibiotic therapy')
For most patients with GAS bacteremia in the absence of shock, organ failure, or necrotizing infection, we suggest initial combination therapy with a beta-lactam (eg, penicillin G) plus clindamycin rather than penicillin monotherapy (Grade 2C). GAS is exquisitely susceptible to beta-lactam antibiotics. The rationale for adding clindamycin is that it suppresses toxin production and may reduce the risk of treatment failure. Clindamycin should not be used as a monotherapy for invasive GAS infection, because it is not bactericidal and because the prevalence of clindamycin resistance is rising among GAS isolates. Linezolid is an acceptable alternative to clindamycin and may be preferred if clindamycin resistance is a concern.
The minimum duration of treatment is at least 14 days. However, in patients with serious soft tissue infection (eg, necrotizing fasciitis), the length of therapy depends upon the clinical response to treatment. (See 'Duration of therapy' above.)
•Surgical intervention – If there is a focal site of infection (eg, necrotizing soft tissue infection, osteomyelitis, septic arthritis, empyema), appropriate surgical specialists should be consulted to determine whether the patient requires surgical exploration, drainage, and/or resection of necrotic tissue. (See "Surgical management of necrotizing soft tissue infections" and "Hematogenous osteomyelitis in children: Management", section on 'Indications for surgery' and "Bacterial arthritis in infants and children: Treatment and outcome", section on 'Drainage' and "Management and prognosis of parapneumonic effusion and empyema in children", section on 'Surgical therapy'.)
•Intravenous immune globulin (IVIG) – IVIG is suggested for patients with severe invasive GAS infections (ie, TSS or necrotizing soft tissue infection). This is discussed separately. (See "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'Intravenous immune globulin' and "Necrotizing soft tissue infections", section on 'Intravenous immune globulin'.)
●Prognosis – The mortality rate in children with invasive GAS infection is approximately 2 to 8 percent; long-term disability occurs in an additional 3 to 8 percent. (See 'Prognosis' above.)
