Simplifying the Science: The Treatment of Group A Streptococcal Infections

Column Author: Phil Jurasinski, DO | Internal Medicine-Pediatrics Resident

Column Editor: Rana El Feghaly, MD, MSCI | Pediatric Infectious Diseases | Director, Clinical Services; Director, Outpatient Antibiotic Stewardship Program

Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Clinical Assistant Professor of Pediatrics, University of Kansas School of Medicine

Streptococcus pyogenes, also known as group A streptococcus (GAS), is a familiar pathogen for almost all pediatric providers. GAS infection typically presents as either non-invasive or invasive forms of infections. Non-invasive infections include streptococcal pharyngitis and impetigo. Invasive GAS infections may present in other ways including isolated bacteremia, deep-seated abscesses, pneumonia, necrotizing fasciitis and streptococcal toxic shock syndrome.¹ We saw an increase in invasive disease early this year coincident with the early influenza season, and are currently seeing high rates of GAS pharyngitis.

What is the epidemiology of invasive group A streptococcal infections? 

Invasive GAS has been on the rise nationally for the past several years, with 15,000 cases in both 2014 and 2015, 18,000 cases in 2016, and 23,000-25,000 cases yearly in 2017-2019.¹ Many of these infections have presented as cellulitis (38.6%-48.7% of cases), with the number of bacteremia, pneumonias, necrotizing fasciitis and streptococcal toxic shock syndrome remaining roughly the same at 21%, 14%, 6% and 3%, respectively.¹ In December 2022, the Centers for Disease Control and Prevention (CDC) released a statement that it was investigating an increase in invasive GAS infections nationally.² The World Health Organization also reported an increase in invasive GAS infections from around the globe at around the same time. Similarly, at Children’s Mercy, we have treated multiple children with invasive GAS infections this winter. Worth remembering is that these invasive infections do not routinely begin as GAS pharyngitis.  

How is group A streptococcal pharyngitis diagnosed? 

GAS pharyngitis typically occurs in children 5-15 years old. Many viral infections feature pharyngitis, such as Epstein-Barr virus, adenovirus, coronaviruses and rhinoviruses. Centor criteria are usually inaccurate for children under the age of 15.⁴ Patients with viral symptoms such as cough, rhinorrhea, oral ulcers or hoarseness should not be tested for GAS pharyngitis.^3,4 Children under the age of 3 should not be tested unless there is a known close GAS exposure (e.g., older sibling in the home). Since viral pharyngitis can present with fever and sore throat only and be indistinguishable from GAS clinically, the diagnosis of GAS pharyngitis should always be confirmed. Rapid antigen detection tests are highly specific; if positive, the diagnosis is confirmed. However, if the result is negative, a back-up throat culture is currently still recommended for confirmatory testing.⁴ Polymerase chain reaction testing is also available commercially and is highly sensitive. Neither of these methods distinguishes colonization from true disease, thus the importance of testing only when indicated. Data from Children’s Mercy for the past several weeks show a significant increase in the numbers of positive tests for GAS pharyngitis along with an increase in positivity rate up to 60%. Other pediatric institutions around the country are reporting similar increases with reported positivity rates of up to 80%. 

Why treat group A streptococcal pharyngitis? 

Non-invasive GAS can rarely lead to significant morbidity and mortality, such as rheumatic heart disease and poststreptococcal glomerulonephritis; it can lead to local suppurative complications such as peritonsillar abscess.^3,4 The risk of rheumatic fever from GAS pharyngitis is exceedingly rare in most developed countries (approximately one case per 100,000 school-aged children compared to 19 per 100,000 school-aged children worldwide). Whether antibiotics are recommended to treat every case of GAS pharyngitis remains a controversial topic.⁵ In the U.S., our national guidelines continue to recommend antibiotic therapy for GAS pharyngitis.⁴  

What are the treatment options for GAS infections? 

Penicillin-based antibiotics continue to be the gold standard for GAS, with universal susceptibility. For GAS pharyngitis, we recommend a once-daily dose of amoxicillin (50 mg/kg) for 10 days; twice or three times a day dosing of penicillin VK for 10 days; or a one-time dose of IM benzathine penicillin G. For patients with non-severe penicillin allergy, a first-generation cephalosporin such as cephalexin would be an appropriate alternative to penicillin.⁴ Macrolides have traditionally been considered a second-line antibiotic option for those with severe penicillin allergy, followed by lincosamide antibiotics such as clindamycin, but resistance patterns are on the rise. One study that examined the CDC’s Active Bacterial Core Surveillance found that in 2017, erythromycin and clindamycin resistance among invasive isolates were at 22.8% and 22.0%, respectively.⁶ Resistance to these two antibiotics has further increased to 29% as of 2020.¹  

What are alternatives for treatment considering the amoxicillin shortage? 

Local pediatricians have done an amazing job prescribing appropriate antibiotics during the antibiotic shortages we have all been facing for the last few months. For children <27 kg, penicillin VK 250 mg twice or three times daily for 10 days or a one-time dose of 600,000 units of IM penicillin G benzathine are excellent options.⁷ For children ≥27 kg, it is recommended to prescribe 500 mg of penicillin VK twice daily for 10 days or a one-time dose of 1,200,000 units of IM penicillin G.⁷ Cephalexin 40 mg/kg/day divided twice daily (max 500 mg/dose) is an alternative for patients with penicillin allergy.⁷ A one-time dose of IM ceftriaxone, which can be used for the treatment of acute otitis media, has not been studied for GAS pharyngitis and so should not be used.  

In conclusion, although invasive GAS infections are on the rise, outside of peritonsillar abscess, these infections generally do not arise from pharyngitis. Thus, we should continue to be diligent in testing only patients who meet clinical criteria for streptococcal testing. Penicillin and amoxicillin remain the drugs of choice to treat GAS pharyngitis. First-generation cephalosporins are appropriate alternatives except in cases of severe allergies, where azithromycin and clindamycin may be appropriate options, although resistance rates are increasing. A one-time dose of ceftriaxone has not been studied or recommended for management of GAS pharyngitis. 

References: 

1. Active bacterial core surveillance (ABCs). Centers for Disease Control and Prevention. Accessed January 22, 2023. https://www.cdc.gov/abcs/bact-facts-interactive-dashboard.html 
2. Increase in invasive group A strep infections, 2022-2023. Centers for Disease Control and Prevention. Accessed January 14, 2023. https://www.cdc.gov/groupastrep/igas-infections-investigation.html  
3. Randel A; Infectious Disease Society of America. IDSA updates guideline for managing group A streptococcal pharyngitis. Am Fam Physician. 2013;88(5):338-340. 
4. Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55(10):e86-e102. 
5. Mustafa Z, Ghaffary M. Diagnostic methods, clinical guidelines, and antibiotic treatment for group A streptococcal pharyngitis: a narrative review. Front Cell Infect Microbiol. 2020;10:563627. 
6. Fay K, Onukwube J, Chochua S, et al. Patterns of antibiotic nonsusceptibility among invasive group A Streptococcus infections—United States, 2006–2017. Clin Infect Dis. 2021;73(11):1957-1964. 
7. American Academy of Pediatrics. Amoxicillin shortage: antibiotic options for common pediatric conditions. Red Book Online. American Academy of Pediatrics. November 21, 2022. Accessed January 14, 2023. https://publications.aap.org/redbook/resources/22761