Amoxicillin Dosing for Strep Throat: Once Daily vs. Twice Daily
For strep throat, amoxicillin can be dosed either 50 mg/kg once daily (maximum 1000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose), both for 10 days—these regimens are equally effective and both carry a "strong, high" recommendation from the Infectious Diseases Society of America. 1, 2
Primary Dosing Options
Both dosing strategies are explicitly endorsed as first-line treatment options with equal strength of recommendation:
- Once-daily dosing: 50 mg/kg once daily (maximum 1000 mg) for 10 days 1, 2
- Twice-daily dosing: 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days 1, 2
For adults, this translates to either 1000 mg once daily or 500 mg twice daily for 10 days 2
Evidence Supporting Once-Daily Dosing
The once-daily regimen is not inferior to more frequent dosing schedules:
- Meta-analysis of randomized controlled trials demonstrates that once-daily amoxicillin achieves bacteriologic cure rates equivalent to twice-daily amoxicillin or three-times-daily penicillin V, with no statistically significant differences in clinical failure rates or adverse effects 3
- Clinical trials show bacteriologic treatment failure rates of 5% with once-daily amoxicillin versus 11% with three-times-daily penicillin V, demonstrating non-inferiority 4
- Once-daily amoxicillin specifically (unlike once-daily penicillin) maintains efficacy comparable to more frequent dosing regimens 5
Clinical Decision-Making Algorithm
Choose once-daily dosing when:
- Compliance concerns exist, as simplified regimens improve adherence 6, 3
- Cost is a consideration, as conventional amoxicillin once daily is less expensive than other once-daily alternatives like azithromycin or cefadroxil 6
- Patient or family preference favors convenience 4
Choose twice-daily dosing when:
- Traditional dosing is preferred by the prescriber or patient 1
- There is concern about achieving adequate drug levels throughout the day, though evidence does not support this concern 3, 5
Critical Treatment Principles
- Complete the full 10-day course regardless of symptom improvement to prevent acute rheumatic fever—this is non-negotiable 1, 2
- Patients become non-contagious after 24 hours of appropriate antibiotic therapy, but treatment must continue for the full duration 2
- Plain amoxicillin (not amoxicillin-clavulanate) is first-line for uncomplicated streptococcal pharyngitis 2
Common Pitfalls to Avoid
- Do not use once-daily penicillin V (as opposed to amoxicillin)—this is associated with cure rates 12 percentage points lower than more frequent dosing and should not be used 5
- Do not substitute amoxicillin-clavulanate for plain amoxicillin in uncomplicated cases, as it adds unnecessary clavulanate exposure and cost 2
- Do not discontinue therapy early even if symptoms resolve, as this increases the risk of acute rheumatic fever 1, 2