What is the first line antibiotic for strep throat?

First-Line Antibiotic for Strep Throat

Penicillin V (250 mg three to four times daily) or amoxicillin (50 mg/kg once daily for children, 500 mg twice daily for adults) for 10 days remains the definitive first-line treatment for strep throat. 1, 2

Primary Treatment Algorithm

For Non-Allergic Patients

Oral penicillin remains the gold standard due to proven efficacy, safety, narrow spectrum, and low cost. 1

• Penicillin V is the drug of choice for adults and older children: 250 mg three to four times daily OR 500 mg twice daily for 10 days 2, 3
• Amoxicillin is equally effective and preferred in young children due to better palatability: 50 mg/kg once daily (maximum 1,000 mg) OR 25 mg/kg twice daily (maximum 500 mg) for 10 days 2, 3, 4
• Intramuscular benzathine penicillin G should be used when oral compliance is uncertain: 1.2 million units as single injection for patients ≥27 kg, or 600,000 units for patients <27 kg 1, 2, 3

The WHO Expert Committee endorsed watchful waiting and symptom relief as the first-choice approach before antibiotics, with amoxicillin or phenoxymethylpenicillin as first-choice antibiotic treatment when bacterial pharyngitis is confirmed. 1

Critical Evidence Supporting Penicillin

Penicillin and amoxicillin reduce the risk of rheumatic fever by 73% (RR 0.27; 95% CI 0.12-0.60) and decrease suppurative complications including acute otitis media (RR 0.30) and peritonsillar abscess (RR 0.15). 1

Higher-dose amoxicillin (40 mg/kg/day) achieves superior bacteriologic cure rates (79.3%) compared to standard-dose penicillin V (54.5%), suggesting that perceived penicillin failures may be due to inadequate dosing. 5

Treatment for Penicillin-Allergic Patients

Non-Immediate (Non-Anaphylactic) Allergy

First-generation cephalosporins are the preferred alternative for patients without immediate hypersensitivity reactions. 6, 2, 3

• Cephalexin: 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days 6, 3
• Cefadroxil: 30 mg/kg once daily (maximum 1 gram) for 10 days 6, 3

Cephalosporins demonstrate lower clinical relapse rates compared to penicillin (OR 0.55; 95% CI 0.31-0.99), though symptom resolution is similar. 1

Immediate/Anaphylactic Allergy

Patients with immediate hypersensitivity must avoid all beta-lactams due to up to 10% cross-reactivity risk with cephalosporins. 6, 3

Clindamycin is the preferred alternative for immediate penicillin allergy:

• Dosing: 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days 6, 2, 3
• Resistance: Approximately 1% in the United States, making it highly reliable 6, 3
• Efficacy: High efficacy in eradicating streptococci, even in chronic carriers 6

Macrolide alternatives (use with caution due to resistance):

• Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days only 6, 2, 3
• Clarithromycin: 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days 6, 3

The FDA label explicitly states that penicillin by intramuscular route is the usual drug of choice, and azithromycin should be used as an alternative when first-line therapy cannot be used. 7

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. 1, 6, 2, 3

• Azithromycin is the only exception, requiring only 5 days due to its prolonged tissue half-life 6, 2, 3
• Therapy can be safely postponed up to 9 days after symptom onset and still prevent acute rheumatic fever 1
• Shortening courses by even a few days results in appreciable increases in treatment failure rates 6

Important Resistance Considerations

Macrolide resistance among Group A Streptococcus ranges from 5-8% in the United States, though this varies geographically and temporally. 6, 3, 4

Short-course macrolide treatment shows greater risk of late bacteriological recurrence (OR 1.31; 95% CI 1.16-1.48) compared to 10-day penicillin courses. 1

Clindamycin resistance remains very low at approximately 1% in the United States, making it an excellent choice for penicillin-allergic patients. 6, 3

Common Pitfalls to Avoid

• Never use azithromycin or macrolides as first-line when penicillin can be used—reserve for documented penicillin allergy 6, 2
• Do not assume all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them 6, 2
• Never prescribe trimethoprim-sulfamethoxazole for strep throat—50% resistance rate makes it ineffective 6, 3
• Do not use sulfonamides or tetracyclines due to high resistance rates and frequent treatment failures 3
• Avoid prescribing shorter courses than recommended (except azithromycin's 5-day regimen)—this leads to treatment failure and complications 6
• Do not routinely perform post-treatment cultures in asymptomatic patients who completed therapy—only consider in special circumstances like history of rheumatic fever 6

Adjunctive Therapy

For symptom management:

• Acetaminophen or NSAIDs (ibuprofen) for moderate to severe symptoms or high fever 6, 3
• Aspirin must be avoided in children due to Reye syndrome risk 6, 3
• Corticosteroids are not recommended as adjunctive therapy 6, 3