Group A streptococcal (GAS) pharyngitis: A practical guide to diagnosis and treatment

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Acute pharyngitis is a common clinical condition that is caused most often by a viral infection. Streptococcus pyogenes (Group A Streptococcus) is the most common bacterial cause of acute pharyngitis, and can be isolated in approximately 20% to 30% of children with pharyngitis in high-income countries ^[1]. GAS pharyngitis occurs most often in children 5 to 11 years of age and during winter and spring months each year ^[2].

Asymptomatic carriage of GAS in children ≥5 years of age is 11% to 15%. However, carriage alone is associated with a low risk for GAS transmission and does not appear to be associated with an increased risk of acute rheumatic fever (ARF) or other complications ^[1][2].

Why we treat: Complications of GAS pharyngitis

GAS pharyngitis can lead to suppurative complications, including peritonsillar and retropharyngeal abscess, and sepsis. Non-suppurative complications, such as post-streptococcal glomerulonephritis and ARF, are postulated to result from aberrant immune reactions in tissues following immunologically significant GAS infection (i.e., when anti-GAS antibodies are produced) ^[3]. Antibiotic treatment of GAS pharyngitis has been shown to prevent suppurative complications and ARF, but not post-streptococcal glomerulonephritis.

The most serious manifestation of ARF is rheumatic heart disease (RHD), which can cause irreversible damage to heart valves. ARF is diagnosed using the revised Jones criteria, which differentiate between high risk and low to medium risk populations ^[4]. ARF incidence and severity appear to be influenced by environmental and pathogen- and host-specific factors. Certain M protein types (a key virulence factor) are associated with ARF-causing GAS strains ^[5][6].

Although the incidence and prevalence of ARF and RHD have decreased significantly in high-income countries, they remain important causes of morbidity and mortality in low- and middle-income countries and in Indigenous populations worldwide. One Canadian study reported an overall ARF incidence of 0.3 per 100,000 children per year, compared with a much higher incidence of 21.3 per 100,000 in a community of First Nations peoples in northern Ontario ^[7][8].

This inequity of disease burden for ARF between Indigenous and non-Indigenous populations is multifactorial, with many studies suggesting that limited access to health care and poor living conditions contribute to increased risk of ARF ^[5][7]. In settings where the disease burden is high, interventions to improve living conditions, ensure early diagnosis and treatment of GAS pharyngitis through public and health care provider education, and improve access to medical care have been shown to reduce ARF incidence ^[5][9].

Who to test: Clinical presentation and diagnosis

GAS pharyngitis is characterized by fever >38.0°C, moderate to severe sore throat, very tender anterior cervical lymphadenopathy, absence of cough and rhinorrhea, and inflamed and/or purulent tonsils. Clinical presentation varies considerably among studies and countries ^[10]. Symptoms are generally self-limited, resolving without treatment in 4 to 5 days. GAS pharyngitis is rare in children <3 years of age, and testing is only indicated in outbreak settings or when scarlet fever is suspected.

Positive throat cultures in children with symptoms of viral upper respiratory infection (i.e., rhinorrhea, cough) and sore throat often indicate GAS carriage in the setting of viral pharyngitis. Antimicrobial stewardship initiatives, including Choosing Wisely Canada, promote judicious use of investigations and antibiotics when pre-test probability is low ^[11]. Clinical decision rules, such as CENTOR (Box 1), can assist in identifying patients with higher risk for GAS who warrant testing. These are not treatment criteria, however ^[12][13].

Box 1. CENTOR Clinical decision rule

(only for children aged 3 to 14 years)

One point for each characteristic: Exudate or swollen tonsils Tender or  swollen anterior cervical lymph nodes Fever No cough If the total score is ≥3, do a throat swab. There is a 32% to 56% probability of GAS infection in such cases.

Based on reference [13]

For children with a high pre-test probability of having GAS pharyngitis (e.g., a CENTOR score ≥3), microbiological diagnosis is important to limit inappropriate antibiotic use ^[14][15]. The gold-standard test is bacterial culture from a swab of the tonsils and posterior pharyngeal wall. Point-of-care rapid antigen detection tests (RADTs) have a rapid turnaround time (about 1 hour) and high specificity (>95% reported in individual studies). Their somewhat lower sensitivity of 86% may be acceptable in low ARF burden settings, but in high burden settings, a negative RADT should be confirmed by culture ^[16]. In rare circumstances, criteria for acute pharyngitis associated with systemic toxicity may warrant treatment, provided that cultures are done. Anti-streptolysin O titer (ASOT) should not be used to diagnose GAS pharyngitis because it cannot distinguish GAS carriage from active infection ^[2].

When and how to treat GAS pharyngitis

Although GAS pharyngitis is self-limited, treatment is indicated within 9 days of symptom onset to prevent ARF and suppurative complications ^[17]. Antibiotic stewardship can be achieved by providing delayed antibiotic prescriptions (i.e., to be filled only for children with positive cultures). One Cochrane Review associated delayed antibiotics with similar patient satisfaction and no increase in ARF or suppurative complications, compared with empiric antibiotics based on clinical judgement ^[15].

Antibiotics

The optimal treatment for GAS pharyngitis continues to be penicillin or amoxicillin for 10 days, because all Group A streptococci are susceptible to penicillin (Table 1). Amoxicillin can be dosed once daily and a suspension is available (unlike penicillin V) ^[18]. For children with non-anaphylactic hypersensitivity reactions to penicillins, an oral amoxicillin challenge or cephalexin is recommended ^[19]. For the very rare patient with a clear history of anaphylaxis or documented type 1 hypersensitivity to penicillins, acceptable options are azithromycin, clarithromycin, and clindamycin. However, resistance to macrolides and clindamycin has been documented in up to 20% of isolates.

Table 1. Treatment choices for laboratory-confirmed Group A streptococcal pharyngitis
Population	Drug and dose	Duration
Most children (no history of type I hypersensitivity to penicillins)	Penicillin V (no oral suspension available) ≤27 kg: 300 mg per dose by mouth, 2 or 3 times per day Over 27 kg: 600 mg per dose by mouth, 2 or 3 times per day	10 days
	Amoxicillin 50 mg/kg by mouth once daily (or 25 mg/kg 2 times daily) to a maximum 1 g per day	10 days
For children expected to have difficulty adhering to a 10-day course of antibiotics	Penicillin G Benzathine Intramuscular <27 kg: 600,000 units or ≥27 kg: 1,200,000 units	1 dose
Children with non-anaphylactic type I hypersensitivity to penicillins	Oral amoxicillin challenge OR Cephalexin 20 mg/kg/dose 2 times per day	10 days
Children with documented anaphylaxis to penicillins*	Clarithromycin 7.5 mg/kg/dose 2 times per day ( to a maximum 250 mg/dose)	10 days
	Azithromycin 12 mg/kg/day once daily (to a maximum 500 mg)	5 days
	Clindamycin 5 to 10 mg/kg/dose every 6 to 8 hours	10 days
* Confirm local antimicrobial susceptibility whenever possible, due to high rates of regional resistance

Symptomatic management

Acetaminophen or ibuprofen are recommended for symptom management. Dexamethasone has been studied as an adjunct therapy for pain relief ^[20], but most guidelines recommend against corticosteroid use due to low quality evidence and safety concerns ^[2][12][21].

Management of GAS carriage and recurrent GAS infection

A challenging clinical problem is that of children who experience recurrent sore throat and have positive throat cultures for GAS, or who have recurring GAS infection. Although some children truly have recurring GAS pharyngitis, many others may be chronic GAS carriers. Teasing out this distinction requires careful assessment of the clinical situation, including adherence to the treatment regimen and time of response to therapy. For GAS pharyngitis, rapid clinical improvement in ≤24 hours is expected, while viral pharyngitis with incidental GAS carriage improves more gradually, over 2 to 3 days ^[12].

Repeating throat culture after treatment or performing cultures on asymptomatic children is generally not recommended. Exceptions might include families with members at risk for ARF or who appear to be passing GAS infections back and forth, or during a GAS outbreak in a closed community. In such situations, performing throat culture when the child has an asymptomatic interval may distinguish chronic GAS carriers from those with recurrent, discontinuous infections. In high-risk situations, a trial of eradication therapy may be warranted, but even when successful initially, GAS carriage is frequently re-acquired. Suggested agents for eradication therapy include a 10-day course of amoxicillin-clavulanate or clindamycin, or, alternately, penicillin or amoxicillin for 10 days with rifampin for the final 4 days ^[17].

Special considerations for populations with known or potential high risk for ARF

In populations at higher risk for ARF, such as children living in the Canadian North or in overcrowded housing conditions, and Indigenous and Pacific Islander children, a high index of clinical suspicion for GAS is needed ^[22]. For these children, the risks of acquiring or worsening ARF may exceed the risks of selective testing and treatment as currently recommended for populations at low risk for ARF. Widespread availability of RADT could increase detection of GAS pharyngitis in rural, remote, or under-resourced communities. However, access to throat culture is important to rule out false negative RADT results ^[2][16]. In situations where no testing is available, consider empiric treatment for children with CENTOR scores >3.

Crucially, improving access to health services, having adequate supply of oral penicillin and amoxicillin, providing education about GAS and ARF, and addressing housing needs are essential to ensure health equity for First Nations, Inuit, and Métis children and other populations at higher risk of ARF. More research is needed to understand the burden of ARF in Canada’s Indigencous populations.

Recommendations

Testing for GAS pharyngitis is recommended for children presenting with moderate to severe sore throat, fever, absence of cough and rhinorrhea, and purulent and/or inflamed tonsils.

Microbiological confirmation of GAS pharyngitis using RADT and/or culture is recommended before initiating antimicrobial therapy in low-risk populations. Treatment of first choice for GAS pharyngitis is 10 days of amoxicillin or penicillin.

In communities at high risk for ARF (and specifically in northern or Indigenous communities), testing should be considered in any child ≥3 years of age presenting with sore throat. When testing is not available, empiric treatment of children with higher clinical scores (e.g., CENTOR score ≥3) should be considered in select settings.

Acknowledgements

The authors wish to acknowledge Drs. Tobey Audcent and Margaret Sampson, with the Children’s Hospital of Eastern Ontario, for their background work for this document. This practice point was reviewed by the Community Paediatrics and First Nations, Inuit and Métis Health Committees of the Canadian Paediatric Society, as well as by members of AMMI Canada’s Indigenous Health Committee.

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CANADIAN PAEDIATRIC SOCIETY INFECTIOUS DISEASES AND IMMUNIZATION COMMITTEE

Members: Michelle Barton MD; Sean Bitnun MD; Shalini Desai MD (past member); A. Michael Forrester MD (past member); Ruth Grimes MD (Board Representative); Laura Sauve MD (Chair); Karina A. Top MD
Liaisons: Fahamia Koudra MD, College of Family Physicians of Canada; Marc Lebel MD, Immunization Monitoring Program, ACTive (IMPACT); Yvonne Maldonado MD, Committee on Infectious Diseases, American Academy of Pediatrics; Jane McDonald MD, Association of Medical Microbiology and Infectious Disease Canada; Dorothy L Moore MD, National Advisory Committee on Immunization (NACI); Howard Njoo MD, Public Health Agency of Canada
Principal authors: Laura Sauve MD, A. Michael Forrester MD, Karina A. Top MD

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References

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Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.