Treatment of Streptococcal Pharyngitis
First-Line Therapy for Non-Allergic Patients
Penicillin V or amoxicillin for 10 days is the gold standard treatment for strep throat in patients without penicillin allergy. 1, 2
Dosing Regimens
Adults:
- Penicillin V 250 mg orally 2–3 times daily (or 500 mg twice daily) for 10 days 1
- Amoxicillin 500 mg orally twice daily for 10 days 2
Children:
- Penicillin V 250 mg orally 2–3 times daily for 10 days 1
- Amoxicillin 50 mg/kg once daily (maximum 1000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days 3, 2
Amoxicillin is often preferred over penicillin V in children because of better palatability and more convenient dosing, though both have identical efficacy. 1, 2 Higher-dose amoxicillin (40–50 mg/kg/day) achieves superior clinical cure rates (88% vs 71%) and bacteriologic eradication (79% vs 55%) compared with lower-dose penicillin V. 3, 4
Why Penicillin Remains First-Line
- Zero documented resistance worldwide – no Group A Streptococcus resistance to penicillin has ever been reported 1, 5
- Narrow antimicrobial spectrum minimizes selection of resistant flora 1, 5
- Proven efficacy in preventing acute rheumatic fever 1, 5
- Lowest cost among all options 1, 5
- Excellent safety profile 1
Intramuscular Option for Compliance Concerns
Benzathine penicillin G as a single intramuscular dose is preferred when adherence to oral therapy is uncertain: 1, 2
Treatment for Penicillin-Allergic Patients
Step 1: Determine Type of Allergic Reaction
The type of penicillin reaction dictates which alternatives are safe. 3
Immediate/anaphylactic reactions (anaphylaxis, angioedema, urticaria within 1 hour) carry up to 10% cross-reactivity with all beta-lactams including cephalosporins – these patients must avoid all beta-lactam antibiotics. 3, 2
Non-immediate/delayed reactions (mild rash >1 hour after exposure) have only 0.1% cross-reactivity with first-generation cephalosporins – these patients can safely receive cephalosporins. 3
For Non-Immediate Penicillin Allergy
First-generation cephalosporins are the preferred alternatives with strong, high-quality evidence: 3, 2
Adults:
- Cephalexin 500 mg orally twice daily for 10 days 3, 2
- Cefadroxil 1 gram orally once daily for 10 days 3
Children:
- Cephalexin 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days 3, 2
- Cefadroxil 30 mg/kg once daily (maximum 1 gram) for 10 days 3
For Immediate/Anaphylactic Penicillin Allergy
Clindamycin is the preferred choice with only ~1% resistance among U.S. Group A Streptococcus isolates and superior eradication rates even in chronic carriers: 3, 2
Adults:
Children:
Macrolide alternatives (less preferred due to 5–8% resistance in the United States): 3, 5
Azithromycin:
- Adults: 500 mg orally once daily for 5 days 3, 2
- Children: 12 mg/kg once daily (maximum 500 mg) for 5 days 3, 2
Clarithromycin:
- Adults: 250 mg orally twice daily for 10 days 3
- Children: 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days 3
Erythromycin (least preferred due to high gastrointestinal side effects):
- Erythromycin estolate: 20–40 mg/kg/day divided 2–3 times daily (maximum 1 gram/day) for 10 days 1, 3
- Erythromycin ethylsuccinate: 40 mg/kg/day divided 2–3 times daily for 10 days 1
Critical Treatment Duration Requirements
A full 10-day course is mandatory for all antibiotics except azithromycin to achieve maximal pharyngeal eradication and prevent acute rheumatic fever. 3, 2, 5 Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk, even when symptoms resolve within 3–4 days. 3, 5
Azithromycin is the only exception, requiring only 5 days due to its prolonged tissue half-life. 3, 2
Therapy can be safely postponed up to 9 days after symptom onset and still prevent acute rheumatic fever. 3, 5
Treatment of Recurrent/Persistent Infections
For patients who fail initial therapy or chronic carriers, clindamycin is substantially more effective than penicillin or amoxicillin in eliminating chronic streptococcal carriage: 3, 2
Clindamycin:
- Children: 20–30 mg/kg/day divided three times daily for 10 days 2
- Adults: 600 mg/day in 2–4 equally divided doses for 10 days 2
Amoxicillin-clavulanate:
- 40 mg/kg/day (amoxicillin component) divided three times daily (maximum 2000 mg amoxicillin/day) for 10 days 3, 2
Penicillin V plus rifampin:
- Penicillin V 50 mg/kg/day divided four times daily (maximum 2000 mg/day) for 10 days
- Plus rifampin 20 mg/kg/day once daily for the final 4 days (maximum 600 mg/day) 3
Adjunctive Symptomatic Treatment
Acetaminophen or NSAIDs (ibuprofen) should be offered for moderate to severe symptoms or high fever. 3, 2, 5 These provide modest benefit, shortening sore throat duration by only 1–2 days. 5
Aspirin is acceptable in adults but must be avoided in children due to Reye syndrome risk. 3, 2, 5
Corticosteroids are not recommended as adjunctive therapy. 3
Common Pitfalls to Avoid
- Do not prescribe cephalosporins to patients with immediate/anaphylactic penicillin reactions due to 10% cross-reactivity risk 3, 2
- Do not shorten the antibiotic course below 10 days (except azithromycin's 5-day regimen) as this markedly increases treatment failure and rheumatic fever risk 3, 2, 5
- Do not use trimethoprim-sulfamethoxazole (Bactrim) – sulfonamides fail to eradicate Group A Streptococcus in 20–25% of cases 3
- Do not use tetracyclines – they fail to eradicate the organism and do not prevent rheumatic fever 1, 3
- Do not prescribe broad-spectrum antibiotics when narrow-spectrum penicillin/amoxicillin is appropriate, as this unnecessarily selects for resistant flora 1, 5
- Do not order routine post-treatment throat cultures for asymptomatic patients who completed therapy; reserve testing for special circumstances such as history of rheumatic fever 3
Antibiotics to Avoid
The following agents should NOT be used for streptococcal pharyngitis: