What are the first-line antibiotics for an otherwise healthy patient with strep throat?

First-Line Antibiotics for Strep Throat

Penicillin V (250 mg three to four times daily or 500 mg twice daily for 10 days) or amoxicillin (500 mg twice daily for 10 days) are the first-line antibiotics for otherwise healthy patients with strep throat. 1, 2

Why Penicillin/Amoxicillin Remain First-Line

• Penicillin has been the drug of choice for streptococcal pharyngitis for over four decades, with proven efficacy, narrow spectrum of activity, safety, and low cost 1, 2, 3
• No documented penicillin resistance in Group A Streptococcus exists anywhere in the world 4
• Amoxicillin is equally effective to penicillin V and is preferred in younger children due to better palatability and availability as suspension 1, 2
• The twice-daily dosing of penicillin V (500 mg) is as effective as three or four times daily dosing, improving compliance 5

Critical Treatment Duration

• A full 10-day course is essential to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever 4, 1, 2
• Early treatment can reduce symptom duration to less than 24 hours in most cases, decrease suppurative complications, and limit disease spread 3
• Shortening the course by even a few days dramatically increases treatment failure rates and rheumatic fever risk 4

Alternative for Penicillin-Allergic Patients

Non-Immediate (Non-Anaphylactic) Penicillin Allergy

• First-generation cephalosporins are the preferred alternatives, specifically cephalexin 500 mg twice daily for 10 days or cefadroxil 1 gram once daily for 10 days 4, 1
• Cross-reactivity risk is only 0.1% in patients with non-severe, delayed penicillin reactions 4
• These have strong, high-quality evidence for efficacy, narrow spectrum, and low cost 4, 1

Immediate/Anaphylactic Penicillin Allergy

• Clindamycin 300 mg three times daily for 10 days is the preferred choice 4, 1
• Clindamycin has only ~1% resistance among Group A Streptococcus in the United States and demonstrates high efficacy even in chronic carriers 4
• Azithromycin 500 mg once daily for 5 days is an acceptable alternative, but macrolide resistance is 5-8% in the United States 4, 6
• Patients with immediate hypersensitivity must avoid all beta-lactam antibiotics, including cephalosporins, due to up to 10% cross-reactivity risk 4

When to Treat with Antibiotics

• Antibiotics should not be used in patients with 0-2 Centor criteria to relieve symptoms 7
• For patients with 3-4 Centor criteria, discuss the modest benefits versus side effects, resistance concerns, and costs 7
• Sore throat should not be treated with antibiotics solely to prevent rheumatic fever in low-risk patients with no previous history 7

Common Pitfalls to Avoid

• Do not use azithromycin or other macrolides as first-line when penicillin can be used - reserve these for documented penicillin allergy 4, 1, 6
• Do not assume all penicillin-allergic patients cannot receive cephalosporins - only those with immediate/anaphylactic reactions should avoid them 4, 1
• Do not prescribe shorter courses than 10 days (except azithromycin's 5-day regimen) - this increases treatment failure and rheumatic fever risk 4, 1
• Do not use trimethoprim-sulfamethoxazole (Bactrim) for strep throat - it has high resistance rates and is not recommended 4

Intramuscular Alternative

• Benzathine penicillin G 1.2 million units as a single intramuscular injection is preferred when compliance with 10-day oral therapy is unlikely 1, 3
• This remains the gold standard in areas where rheumatic fever is prevalent, particularly in populations where follow-up may be lacking 3