What is the recommended treatment for streptococcal (strep) throat using penicillin?

Penicillin Treatment for Streptococcal Pharyngitis

Penicillin V remains the drug of choice for strep throat, dosed at 500 mg twice daily (or 250 mg four times daily) for a full 10 days in adolescents and adults, or 250 mg twice to three times daily for 10 days in children. 1

Why Penicillin Remains First-Line

Penicillin has been the treatment of choice for streptococcal pharyngitis for over five decades due to its proven efficacy, safety, narrow spectrum, and low cost 2, 1. Critically, Group A Streptococcus has never developed resistance to penicillin anywhere in the world, with no increase in minimal inhibitory concentrations over at least five decades 2. This makes it superior to alternatives despite the availability of newer antibiotics.

Specific Dosing Regimens

For Children:

• Penicillin V: 250 mg twice or three times daily for 10 days 1
• Amoxicillin (alternative): 50 mg/kg once daily (maximum 1,000 mg) OR 25 mg/kg twice daily (maximum 500 mg) for 10 days 1

For Adolescents and Adults:

• Penicillin V: 250 mg four times daily OR 500 mg twice daily for 10 days 1

When Compliance is Uncertain:

• Intramuscular benzathine penicillin G: 600,000 units (single dose) for patients <27 kg, or 1,200,000 units (single dose) for patients ≥27 kg 1

Critical Treatment Duration

A full 10-day course is mandatory to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever. 1 Twice-daily dosing of penicillin is as efficacious as more frequent dosing regimens 3, but once-daily penicillin dosing is associated with significantly decreased efficacy and should not be used 3, 4.

Why Amoxicillin is Often Preferred in Young Children

Amoxicillin is equally effective to penicillin and often preferred in young children due to better palatability and availability as suspension 2, 1. However, amoxicillin should be avoided in older children and adolescents due to the risk of severe rash in patients with undiagnosed Epstein-Barr virus infection 2.

Treatment Goals Beyond Symptom Relief

The primary goals of antibiotic therapy are preventing acute rheumatic fever and suppurative complications (peritonsillar abscess, acute otitis media, acute sinusitis), not just symptomatic improvement 2, 1. Antibiotics reduce the risk of rheumatic fever by 73% (RR 0.27; 95% CI 0.12-0.60) and decrease the incidence of acute otitis media within 14 days by 70% (RR 0.30; 95% CI 0.15-0.58) 2.

When to Consider Intramuscular Penicillin

In areas where rheumatic fever remains prevalent, particularly in poor and crowded inner-city populations where medical care is episodic, follow-up may be lacking, and compliance with oral penicillin cannot be relied on, intramuscular benzathine penicillin G remains the preferred treatment 1, 5. This single-injection regimen ensures compliance and consistently produces the highest cure rates 5.

Common Pitfalls to Avoid

• Never shorten the course below 10 days: Even a few days' reduction results in appreciable increases in treatment failure rates and rheumatic fever risk 1
• Avoid once-daily penicillin dosing: This is associated with a 12 percentage point lower cure rate (95% CI: 3-21) compared to more frequent dosing 3
• Do not use sulfonamides or tetracyclines: These have high resistance rates and frequent treatment failures 1
• Never use trimethoprim-sulfamethoxazole (Bactrim): This has 50% resistance and is not recommended for Group A Streptococcus 6, 1

Alternatives for Penicillin-Allergic Patients

Non-Immediate Penicillin Allergy:

• First-generation cephalosporins (preferred): Cephalexin 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days, or cefadroxil 30 mg/kg once daily (maximum 1 g) for 10 days 6, 1

Immediate/Anaphylactic Penicillin Allergy:

• Clindamycin (preferred): 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days, with only ~1% resistance in the United States 6, 1
• Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days only, though macrolide resistance is 5-8% in the United States 6, 1

Up to 10% cross-reactivity exists between penicillin and cephalosporins in patients with immediate hypersensitivity, making all beta-lactams unsafe in this group 6, 1.

Adjunctive Therapy

Acetaminophen or NSAIDs (such as ibuprofen) should be considered for moderate to severe symptoms or high fever 6, 1. Aspirin must be avoided in children due to Reye syndrome risk 6, 1. Corticosteroids are not recommended as adjunctive therapy 6, 1.