What is the first line antibiotic treatment for a patient with strep throat, assuming no penicillin allergy or other contraindications?

First-Line Antibiotic for Strep Throat

Penicillin V (250 mg four times daily or 500 mg twice daily) or amoxicillin (50 mg/kg once daily, maximum 1000 mg) for 10 days are the first-line antibiotics for strep throat, with no documented penicillin resistance anywhere in the world. 1, 2, 3

Why Penicillin/Amoxicillin Remain First-Line

The Infectious Diseases Society of America endorses these agents with strong, high-quality evidence based on their proven efficacy, narrow spectrum of activity, excellent safety profile, and low cost. 1, 2, 3 Group A Streptococcus has never developed resistance to penicillin globally, making it uniquely reliable. 3

Specific Dosing Regimens

For adults and adolescents:

• Penicillin V: 250 mg four times daily OR 500 mg twice daily for 10 days 1, 2
• Amoxicillin: 500 mg twice daily for 10 days 1

For children:

• Amoxicillin: 50 mg/kg once daily (maximum 1000 mg) for 10 days 1, 2, 3
• Penicillin V: 250 mg twice or three times daily for 10 days 1

Amoxicillin is often preferred in children due to better palatability and the convenience of once-daily dosing, with equal efficacy to penicillin V. 2, 3

When Compliance Is Uncertain

Intramuscular benzathine penicillin G as a single dose is the preferred option when adherence to oral therapy cannot be assured, particularly in populations where rheumatic fever remains prevalent or follow-up is uncertain. 1, 2

Dosing:

• <27 kg: 600,000 units
• ≥27 kg: 1,200,000 units 1

This single injection ensures complete treatment and remains the gold standard for guaranteed compliance. 1, 2

Critical Treatment Duration

A full 10-day course is essential to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever. 1, 2, 3 Shortening the course by even a few days dramatically increases treatment failure rates and rheumatic fever risk. 4, 2 The primary goal is not just symptomatic improvement but prevention of acute rheumatic fever, which requires adequate bacterial eradication. 4

Alternatives for Penicillin-Allergic Patients

Non-Immediate (Non-Anaphylactic) Penicillin Allergy

First-generation cephalosporins are the preferred alternatives with strong, high-quality evidence. 1, 4, 2, 3

• Cephalexin: 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days 1, 4, 2, 3
• Cefadroxil: 30 mg/kg once daily (maximum 1 gram) for 10 days 1, 4

The cross-reactivity risk with first-generation cephalosporins is only 0.1% in patients with non-severe, delayed penicillin reactions. 4

Immediate/Anaphylactic Penicillin Allergy

All beta-lactam antibiotics must be avoided due to up to 10% cross-reactivity risk in patients with immediate hypersensitivity (anaphylaxis, angioedema, respiratory distress, or urticaria within 1 hour). 1, 4

Clindamycin is the preferred choice with strong, moderate-quality evidence:

• Dosing: 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days 1, 4, 2, 3
• Resistance: Approximately 1% among Group A Streptococcus in the United States 4
• Additional benefit: Particularly effective in chronic carriers who have failed penicillin treatment 4, 3

Macrolides (azithromycin or clarithromycin) are acceptable alternatives but less preferred:

• Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days 1, 4, 2
• Clarithromycin: 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days 1, 4
• Resistance concern: 5-8% macrolide resistance in the United States, varying geographically 1, 4, 2

Critical Pitfalls to Avoid

1. Never prescribe shorter courses than 10 days (except azithromycin's 5-day regimen) as this leads to treatment failure and increased rheumatic fever risk. 4, 2

2. Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to the 10% cross-reactivity risk. 1, 4

3. Avoid trimethoprim-sulfamethoxazole (Bactrim) for strep throat—it is not effective against Group A Streptococcus and should never be used. 4

4. Do not use azithromycin as first-line therapy when penicillin can be used, as there is no data proving it prevents rheumatic fever and resistance rates are concerning. 4, 5

5. Azithromycin requires only 5 days due to its prolonged tissue half-life—do not prescribe 10 days. 1, 4, 2

Adjunctive Therapy

• Acetaminophen or NSAIDs (ibuprofen) should be used for moderate to severe symptoms or high fever 4, 2, 3
• Avoid aspirin in children due to Reye syndrome risk 4, 2, 3
• Do not use corticosteroids as adjunctive therapy 4, 3

Special Consideration: Chronic Carriers

Chronic carriers (asymptomatic patients with persistently positive cultures) generally do not require antimicrobial therapy, as they are unlikely to spread infection or develop complications. 1, 2, 3 If treatment is indicated for chronic carriers, clindamycin is particularly effective due to its ability to eradicate the organism. 4, 2, 3