Penicillin for streptococcal pharyngitis: Is it time for a new paradigm in Canada?

Acute pharyngitis is a common presentation to primary care, accounting for 6% of visits to primary care by children in high-income nations (1). Approximately 20%–40% of pharyngitis in children is caused by group A Streptococcus (GAS) infection (2). However, 60%–70% of children presenting with acute pharyngitis will be prescribed an antibiotic (3,4), suggesting that use of antimicrobial therapy in this setting could be improved. The impact of antimicrobial treatment of pharyngitis on antimicrobial resistance is unknown. Amoxicillin is the antimicrobial most prescribed in the community in Canada (5.08 defined daily doses/1,000 patient days); pharyngitis is the trigger for 5% of antimicrobial prescribing among children aged 0–9 years, and 9% among children aged 10–19 years (5). A study by Malhotra-Kumar et al found that although resistance selection following the use of amoxicillin is modest and short-lived, amoxicillin non-susceptible streptococci increased 2.5-fold within 48 hours of use when compared with placebo (6).

Traditional approaches to antimicrobial stewardship in pharyngitis have optimized laboratory testing for GAS, including the selection of patients for testing using clinical prediction rules (7,8), and the promotion of point-of-care rapid tests to distinguish viral from bacterial pharyngitis (3). Clinical prediction rules do not have adequate diagnostic performance characteristics to eliminate the need for laboratory testing (9). Because GAS colonization occurs in 5%–20% of healthy children, GAS detection is not definitive evidence of disease (8). Adherence to testing guidelines is low in primary care (10). Furthermore, Canada lacks national guidelines for the treatment of acute pharyngitis.

In the setting of increased focus on antimicrobial stewardship and antimicrobial resistance, authors have suggested that antibiotic treatment for streptococcal pharyngitis may not always be justified (11). Treatment suggestions from national guidelines are variable, with American guidelines being more supportive of testing and treatment compared with European guidelines (11).

Because the natural history of untreated streptococcal pharyngitis is clinical resolution, antibiotics contribute only modest improvement in symptoms (12). The primary justification for treatment is the prevention of suppurative complications, including peritonsillar and retropharyngeal abscess, and non-suppurative complications, including acute rheumatic fever (ARF) and post-streptococcal glomerulonephritis (PSGN). While these complications are serious, they are rare in Canada, and an increasing appreciation of the harms of antibiotics adds a new perspective to treatment decisions.

The incidence of pediatric retropharyngeal abscess is increasing in the United States; however, the absolute risk is still extremely low, at 0.22 cases/10,000 people/year (13). ARF incidence in developed countries is <1/100,000 people/year, with a dramatic reduction in the last century. However, most incidence studies were not large enough to be representative, so this estimate may be under-biased. It has been suggested that the reduction in incidence may be due to improvements in hygiene and crowding, and the emergence of less rheumatogenic strains. Although often cited, the decreased incidence of ARF was not solely attributable to antibiotic treatment alone, because it began before antibiotics were widely available (14). It is important to note that ARF incidence remains higher among Indigenous populations in Canada (15).

The number of pharyngitis cases needed to treat with penicillin to prevent one case of rheumatic fever is 53 (16), reflecting that although relative risk reduction is high, this complication may be too rare to justify treatment. Of the 16 studies of penicillin efficacy for the prevention of ARF included in the 2013 Cochrane review, 9 studies observed no ARF in the placebo group. The most recent study containing ARF cases in the placebo group was published in 1961 (12). Treatment of pharyngitis relieves symptoms modestly. After one week of symptoms, 90% of patients were symptom-free, and the number needed to treat to prevent symptoms at one week was 21 (12).

In comparison, the number needed to harm with antibiotics is low. Antimicrobials are responsible for more adverse events than chemotherapy (17). Antimicrobials were the most common cause of medication-related visits to the emergency department in Vancouver, British Columbia (18).

Current treatment guidelines in the United Kingdom, the Netherlands, Belgium, Germany, and Scotland recommend selective treatment for GAS pharyngitis among patients at risk for complications only, such as immunocompromised children, children with previous ARF, or in the setting of a GAS outbreak. It could be argued that Indigenous children in Canada would also benefit from treatment if local ARF incidence approximates ARF incidence in developing countries, as recommended in Australia (19).

It may be time in Canada to reconsider the universal treatment approach for streptococcal pharyngitis. As we increasingly understand the negative cost and outcome impacts of antimicrobial resistance in Canada—and the influence that antimicrobial use has on antimicrobial resistance—we may need to consider more selective treatment.

Conflicts of Interest:

The author has no conflicts of interest to declare.

Funding:

No funding was received for this work.

Disclosures:

The author has nothing to disclose.