What is the recommended dosing frequency of amoxicillin (Amox) 50 mg/kg for the treatment of streptococcal pharyngitis, once daily or twice daily?

Amoxicillin 50 mg/kg Once Daily for Streptococcal Pharyngitis

Amoxicillin 50 mg/kg once daily (maximum 1000 mg) for 10 days is an acceptable and effective treatment regimen for streptococcal pharyngitis, with efficacy equivalent to twice-daily dosing. 1

Dosing Options

The IDSA guidelines explicitly state that once-daily amoxicillin (50 mg/kg, maximum 1000 mg) for 10 days has been shown to be effective for GAS pharyngitis in comparative clinical trials, with the advantage of enhanced adherence due to simplified dosing. 1

Alternative dosing includes:

• 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days 2
• For adults: 500 mg twice daily for 10 days 2, 3

Evidence Supporting Once-Daily Dosing

The recommendation for once-daily dosing carries a "strong, high" quality evidence rating from the IDSA. 1 This regimen offers several advantages:

• Narrow spectrum of activity with few adverse effects 2
• Enhanced adherence compared to multiple daily doses 1
• Relatively inexpensive and palatable, particularly important for pediatric patients 1

Meta-analysis data demonstrate that once-daily amoxicillin is not inferior to other dosing schedules, with no statistically significant differences in bacteriologic cure rates or clinical failure. 4 A 2019 molecular study using real-time PCR confirmed that once-daily dosing achieved equivalent bacterial eradication compared to twice or three-times daily regimens. 5

Critical Treatment Considerations

The full 10-day course is essential to prevent acute rheumatic fever, even if symptoms resolve earlier. 1, 2, 6 This duration is non-negotiable for GAS pharyngitis. 1

Patients become non-contagious after 24 hours of appropriate antibiotic therapy. 2, 3

Important Distinction: Penicillin vs Amoxicillin

While once-daily dosing is effective for amoxicillin, this does NOT apply to penicillin V. Meta-analysis shows that once-daily penicillin is associated with a 12 percentage point lower cure rate (95% CI: 3-21) compared to more frequent dosing and should not be used. 7 In contrast, once-daily amoxicillin does not show this decreased efficacy. 7

Clinical Algorithm

For non-penicillin-allergic patients with confirmed GAS pharyngitis:

1. First choice: Amoxicillin 50 mg/kg once daily (max 1000 mg) for 10 days 1, 2
2. Alternative: Amoxicillin 25 mg/kg twice daily (max 500 mg per dose) for 10 days 2
3. For compliance concerns: Consider intramuscular benzathine penicillin G as a single dose 1

Common Pitfalls to Avoid

• Do not use once-daily penicillin V – only amoxicillin has proven efficacy with once-daily dosing 7
• Do not shorten the 10-day course – shorter courses lack sufficient evidence and may not prevent rheumatic fever 1
• Do not exceed maximum doses – 1000 mg daily for once-daily regimen, 500 mg per dose for twice-daily 2, 6
• Do not use broad-spectrum alternatives (cefdinir, cefpodoxime) as first-line – they are more expensive and promote resistance 1