What is the first‑line empirical oral antibiotic regimen for acute bacterial tonsillitis in a child or adult without a penicillin allergy?

First-Line Empirical Antibiotic for Acute Bacterial Tonsillitis

Prescribe oral penicillin V 500 mg twice daily (or 250 mg four times daily) for adults, or amoxicillin 500 mg twice daily for adults, for a mandatory 10-day course; for children, use amoxicillin 50 mg/kg once daily (maximum 1000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days. 1, 2

Why Penicillin or Amoxicillin Remains First-Line

• Penicillin and amoxicillin are the drugs of choice because Group A Streptococcus has never developed resistance to penicillin anywhere in the world, ensuring reliable bacterial eradication. 1, 2

• These agents offer proven efficacy in preventing acute rheumatic fever and suppurative complications (peritonsillar abscess, cervical lymphadenitis), have an excellent safety profile, narrow antimicrobial spectrum, and low cost. 1, 2

• Amoxicillin is preferred over penicillin V in younger children due to better palatability and availability as a liquid suspension, though both have identical efficacy against Group A Streptococcus. 2

Critical Treatment Duration

• A complete 10-day course is mandatory to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever, even if symptoms resolve within 3–4 days. 1, 2, 3

• Shortening the course by even a few days leads to appreciable increases in treatment failure rates and rheumatic fever risk. 1, 2

• Five-day standard-dose penicillin regimens show inferior bacteriologic eradication (OR 0.43; 95% CI 0.23–0.82) and cannot be recommended. 1

Alternatives for Penicillin Allergy

Non-Immediate (Delayed) Penicillin Allergy

• First-generation cephalosporins are the preferred first-line alternatives with strong, high-quality evidence supporting their efficacy. 2, 1

• Cephalexin 500 mg twice daily for adults or 20 mg/kg per dose twice daily (maximum 500 mg) for children, for 10 days. 2, 3

• Cefadroxil 1 gram once daily for adults or 30 mg/kg once daily (maximum 1 gram) for children, for 10 days. 2, 1

• The cross-reactivity risk with first-generation cephalosporins is only 0.1% in patients with non-severe, delayed penicillin reactions (e.g., mild rash). 2, 3

Immediate/Anaphylactic Penicillin Allergy

• All beta-lactam antibiotics must be avoided in patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, urticaria within 1 hour) due to up to 10% cross-reactivity risk. 2, 1, 3

• Clindamycin is the preferred choice with strong, moderate-quality evidence: 300 mg orally three times daily for adults, or 7 mg/kg per dose three times daily (maximum 300 mg) for children, for 10 days. 2, 1

• Clindamycin has only approximately 1% resistance among Group A Streptococcus in the United States and demonstrates high efficacy even in chronic carriers and treatment failures. 2, 1

• Azithromycin 500 mg once daily for adults or 12 mg/kg once daily (maximum 500 mg) for children, for 5 days, is an acceptable alternative but has 5–8% macrolide resistance in the United States. 2, 1

• Clarithromycin 250 mg twice daily for adults or 7.5 mg/kg per dose twice daily (maximum 250 mg) for children, for 10 days, is another macrolide option with similar resistance concerns. 2, 1

• Azithromycin is the only antibiotic requiring just 5 days due to its prolonged tissue half-life; all other agents require the full 10-day course. 2, 1

Common Pitfalls to Avoid

• Do not prescribe antibiotics without confirming bacterial infection—viral pharyngitis is far more common, and features such as cough, rhinorrhea, hoarseness, and oral ulcers suggest a viral etiology. 1, 4

• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to the 10% cross-reactivity risk. 2, 1, 3

• Do not prescribe broad-spectrum cephalosporins (cefdinir, cefixime, cefpodoxime, cefuroxime) when narrow-spectrum first-generation agents are appropriate—they are more expensive and more likely to select for antibiotic-resistant flora. 2, 3

• Do not shorten the antibiotic course below 10 days (except azithromycin's 5-day regimen)—this dramatically increases treatment failure and rheumatic fever risk. 2, 1, 3

• Trimethoprim-sulfamethoxazole should never be used for streptococcal pharyngitis because it fails to eradicate Group A Streptococcus in 20–25% of cases. 2, 1

• Macrolides should be reserved for true penicillin allergy—they should not be used as first-line therapy due to rising resistance rates. 1, 5

Adjunctive Symptomatic Treatment

• Acetaminophen or NSAIDs (such as ibuprofen) should be offered for moderate to severe symptoms or high fever. 2, 3

• Aspirin must be avoided in children due to the risk of Reye syndrome. 2, 3

• Corticosteroids are not recommended as adjunctive therapy for streptococcal pharyngitis. 2, 3

When to Reassess

• If there is no clinical improvement within 48–72 hours of appropriate antibiotic therapy, reassess the diagnosis and consider suppurative complications (peritonsillar abscess, cervical lymphadenitis) or alternative diagnoses. 1, 4

• Routine post-treatment throat cultures are not recommended for asymptomatic patients who have completed therapy; testing should only be considered in special circumstances such as a history of rheumatic fever. 2