What are the recommended antibiotics and dosing for streptococcal pharyngitis in adults and children, and what are the alternatives for patients with penicillin allergy or who are pregnant?

Antibiotic Treatment for Streptococcal Pharyngitis

First-Line Treatment for Non-Allergic Patients

For adults and children without penicillin allergy, amoxicillin or penicillin V remains the drug of choice due to proven efficacy, narrow spectrum, safety, low cost, and zero documented resistance worldwide. 1, 2

Pediatric Dosing (Children ≥3 months and ≥12 weeks)

• 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
• Amoxicillin is preferred over penicillin V in younger children due to better palatability and liquid formulation availability 1
• Alternative: Penicillin V 250 mg twice or three times daily for 10 days 1, 3

Adult Dosing

• Penicillin V 500 mg twice daily OR 250 mg three to four times daily for 10 days 1, 4, 3
• Alternative: Amoxicillin 500 mg twice daily for 10 days 4, 2

Critical Treatment Duration

• A full 10-day course is mandatory for all antibiotics (except azithromycin) to achieve maximal pharyngeal eradication and prevent acute rheumatic fever, even if symptoms resolve within 3-4 days 1, 4
• Shortening the course by even a few days dramatically increases treatment failure rates and rheumatic fever risk 1
• Therapy can be safely postponed up to 9 days after symptom onset and still prevent rheumatic fever 1

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Treatment for Penicillin-Allergic Patients

The choice of alternative antibiotic depends critically on the type of allergic reaction:

Non-Immediate (Delayed) Penicillin Allergy

For patients with delayed, non-anaphylactic reactions (e.g., mild rash occurring >1 hour after exposure), first-generation cephalosporins are the preferred alternative with strong, high-quality evidence. 1, 5

Dosing

• Adults: Cephalexin 500 mg twice daily for 10 days 4, 6
• Children: Cephalexin 20 mg/kg twice daily (maximum 500 mg per dose) for 10 days 1, 6
• Alternative: Cefadroxil 1 gram once daily (adults) or 30 mg/kg once daily (children, maximum 1 gram) for 10 days 1, 4

Rationale

• Cross-reactivity risk with first-generation cephalosporins is only 0.1% in patients with non-severe, delayed penicillin reactions 1, 5
• First-generation cephalosporins have narrower spectrum, lower cost, and stronger evidence than broader-spectrum alternatives 1

Immediate/Anaphylactic Penicillin Allergy

For patients with immediate hypersensitivity (anaphylaxis, angioedema, urticaria within 1 hour, respiratory distress), ALL beta-lactams including cephalosporins must be avoided due to up to 10% cross-reactivity risk. 1, 5

Preferred: Clindamycin

• Adults: Clindamycin 300 mg three times daily for 10 days 4, 5
• Children: Clindamycin 7 mg/kg three times daily (maximum 300 mg per dose) for 10 days 1, 5
• Clindamycin has only ~1% resistance among Group A Streptococcus in the United States and demonstrates superior eradication rates even in chronic carriers 1, 5

Alternative: Azithromycin

• Adults: Azithromycin 500 mg on day 1, then 250 mg daily for days 2-5 4
• Children: Azithromycin 12 mg/kg once daily (maximum 500 mg) for 5 days 1, 7
• Azithromycin is the only antibiotic requiring just 5 days due to its prolonged tissue half-life 1
• Caution: Macrolide resistance ranges from 5-8% in the United States and varies geographically; local resistance patterns should guide use 1, 5

Alternative: Clarithromycin

• Adults: Clarithromycin 250 mg twice daily for 10 days 4
• Children: Clarithromycin 7.5 mg/kg twice daily (maximum 250 mg per dose) for 10 days 1
• Same resistance concerns as azithromycin 1

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Special Populations

Pregnancy

• Penicillin and amoxicillin remain safe and preferred in pregnancy 1
• For penicillin-allergic pregnant women requiring Group B Streptococcus prophylaxis: cefazolin for non-anaphylactic allergy; clindamycin or vancomycin (based on susceptibility) for immediate allergy 1

Treatment Failures or Chronic Carriers

• Clindamycin 300 mg three times daily (adults) or 7 mg/kg three times daily (children) for 10 days is the optimal choice for treatment failures, demonstrating substantially higher eradication rates than penicillin or amoxicillin 1
• Alternative regimens: amoxicillin-clavulanate or penicillin plus rifampin for the last 4 days 1
• Most chronic carriers do not require treatment unless special circumstances exist (community outbreak, family history of rheumatic fever) 1

Patients Unlikely to Complete Oral Therapy

• Intramuscular benzathine penicillin G 1.2 million units as a single dose 1, 4

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Critical Pitfalls to Avoid

• Never use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to 10% cross-reactivity risk 1, 5
• Never shorten the antibiotic course below 10 days (except azithromycin's validated 5-day regimen), as this markedly increases treatment failure and rheumatic fever risk 1, 4
• Never prescribe trimethoprim-sulfamethoxazole (Bactrim) for strep throat—it fails to eradicate Group A Streptococcus in 20-25% of cases 1
• Never use broad-spectrum cephalosporins (cefdinir, cefpodoxime, cefuroxime) when narrow-spectrum first-generation agents are appropriate—they increase cost and select for resistant flora 1
• Never prescribe antibiotics without confirming Group A Streptococcus via rapid antigen test or throat culture, as most pharyngitis is viral 1
• Never order routine post-treatment throat cultures for asymptomatic patients who completed therapy 1, 4

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Adjunctive Symptomatic Management

• Acetaminophen or ibuprofen for moderate to severe symptoms or high fever 1, 4
• Aspirin must be avoided in children due to Reye syndrome risk 1, 4
• Corticosteroids are not recommended as adjunctive therapy 1, 4

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Key Clinical Pearls

• Patients become non-contagious after 24 hours of appropriate antibiotic therapy but must complete the full course 1
• The primary goal of treatment is preventing acute rheumatic fever and suppurative complications, not just symptom relief 1
• Clindamycin resistance remains very low at ~1% in the United States, making it more reliable than macrolides when beta-lactams cannot be used 1, 5
• Consider local macrolide resistance patterns before prescribing azithromycin or clarithromycin 1, 5