What is the first-line treatment for acute pharyngitis?

First-Line Treatment for Acute Pharyngitis

For patients with confirmed Group A Streptococcal (GAS) pharyngitis, penicillin or amoxicillin for 10 days is the first-line treatment, based on their narrow spectrum, proven efficacy, safety profile, and low cost. 1

When to Treat with Antibiotics

• Do not prescribe antibiotics for patients with clinical features strongly suggesting viral etiology, including cough, rhinorrhea, hoarseness, or oral ulcers 1, 2
• Consider testing and treatment when patients present with fever, tonsillar exudate, tender anterior cervical lymphadenopathy, and absence of cough (Centor criteria 3-4) 1, 2, 3
• Testing is generally not recommended for children under 3 years old due to low incidence of GAS pharyngitis and rarity of rheumatic fever in this age group 1, 2

First-Line Antibiotic Regimens for Non-Allergic Patients

Penicillin V (oral):

• Children: 250 mg twice or three times daily for 10 days 1
• Adolescents/adults: 250 mg three to four times daily or 500 mg twice daily for 10 days 1

Amoxicillin (oral):

• Often preferred in young children due to better taste acceptance and twice-daily dosing 1
• Equivalent efficacy to penicillin V 1
• Avoid in older children and adolescents due to risk of severe rash if Epstein-Barr virus infection is present 1

Benzathine penicillin G (intramuscular):

• 1.2 million units as a single dose 1
• Preferred for patients unlikely to complete a 10-day oral course 1

Treatment for Penicillin-Allergic Patients

For non-anaphylactic penicillin allergy:

• First-generation cephalosporins (cephalexin 20 mg/kg/dose twice daily or cefadroxil 30 mg/kg once daily for 10 days) 1, 4, 5
• Up to 10% of patients with immediate hypersensitivity to penicillin may have cross-reactivity with cephalosporins and should avoid them 4

For immediate/anaphylactic penicillin allergy:

• Clindamycin: 7 mg/kg/dose three times daily (max 300 mg/dose) for 10 days 1, 4
• Clarithromycin: 7.5 mg/kg/dose twice daily (max 250 mg/dose) for 10 days 1, 4
• Azithromycin: 12 mg/kg once daily (max 500 mg) for 5 days 1, 4, 6

Critical Considerations About Macrolides

• Macrolide resistance among GAS varies geographically and ranges from 5-8% in the United States 4, 3
• Azithromycin is FDA-approved as an alternative to first-line therapy only when first-line agents cannot be used 6
• Susceptibility testing should be performed when treating with azithromycin due to known resistance 6
• Data establishing efficacy of azithromycin in preventing rheumatic fever are not available 6

Why Penicillin Remains First-Line

The 2012 IDSA guideline and 2024 WHO recommendations consistently prioritize penicillin/amoxicillin because 1:

• No documented resistance of GAS to penicillin over five decades 1
• Narrow spectrum minimizes disruption of normal flora and reduces antimicrobial resistance 1
• Proven efficacy in preventing rheumatic fever and suppurative complications 1
• Minimal adverse effects and low cost 1

Adjunctive Symptomatic Treatment

• NSAIDs or acetaminophen for moderate to severe symptoms or high fever 1, 4
• Avoid aspirin in children due to risk of Reye syndrome 1, 4, 2
• Corticosteroids are not recommended as adjunctive therapy 1, 4

Common Pitfalls to Avoid

• Do not prescribe shorter courses than recommended (except azithromycin 5 days), as this leads to treatment failure and increased complications 4
• Do not assume all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them 4
• Do not routinely perform post-treatment cultures in asymptomatic patients who completed therapy 1, 4
• Do not treat asymptomatic household contacts unless special circumstances exist 1