The impact of dosing frequency on the efficacy of 10-day penicillin or amoxicillin therapy for streptococcal tonsillopharyngitis: A meta-analysis

Pediatrics. 2000 Feb;105(2):E19. doi: 10.1542/peds.105.2.e19.


Objective: The recommended dosing frequency of oral penicillin for the treatment of acute streptococcal tonsillopharyngitis has long been 3 to 4 times daily. In 1994, treatment guidelines included twice-daily (BID) dosing for the first time, a recommendation that could significantly increase the ease of compliance. This meta-analysis was performed to determine whether overall cure rates differed between BID or once-daily (QD) versus more frequent dosing schedules in the treatment of streptococcal tonsillopharyngitis.

Data sources: Candidate studies for this meta-analysis included all clinical trials of therapy for streptococcal tonsillopharyngitis published through August 1998 and identified using Medline, Dissertation Abstracts, conference proceedings, and bibliographies of all retrieved articles.

Study selection: A study was eligible for inclusion if it was a randomized clinical trial that compared the efficacies of different dosing frequencies of 10-day penicillin or amoxicillin in the treatment of streptococcal tonsillopharyngitis. Of the 30 articles initially identified, 6 studies met eligibility criteria.

Outcome measure: The measure of interest was the difference in proportion cured between the BID or QD dosing group and the comparison group with more frequent dosing.

Results: The results of this analysis suggest that BID dosing of 10-day penicillin is as efficacious as more frequent dosing regimens in the treatment of streptococcal tonsillopharyngitis. This result also holds true in a subgroup analysis confined to pediatric cases and does not vary with total daily dose of the regimen. QD dosing of penicillin is associated with a cure rate that is 12 percentage points lower than more frequent dosing (95% confidence interval: 3-21). In contrast, this decreased efficacy is not found with QD dosing of amoxicillin.

Conclusions: This meta-analysis supports current recommendations for BID dosing of penicillin in treating streptococcal tonsillopharyngitis. QD penicillin is associated with decreased efficacy and should not be used. Simplified regimens of amoxicillin of shorter duration or of less frequent dosing should be further investigated.

Publication types

  • Meta-Analysis

MeSH terms

  • Administration, Oral
  • Amoxicillin / administration & dosage*
  • Drug Administration Schedule
  • Humans
  • Penicillins / administration & dosage*
  • Pharyngitis / drug therapy*
  • Pharyngitis / microbiology
  • Streptococcal Infections / drug therapy*
  • Streptococcal Infections / microbiology
  • Streptococcus pyogenes*
  • Tonsillitis / drug therapy
  • Tonsillitis / microbiology
  • Treatment Outcome


  • Penicillins
  • Amoxicillin