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Once-daily amoxicillin versus twice-daily penicillin V in group A β-haemolytic streptococcal pharyngitis
  1. D R Lennon1,
  2. E Farrell2,
  3. D R Martin3,
  4. J M Stewart1
  1. 1
    University of Auckland, Auckland, New Zealand
  2. 2
    Counties Manukau District Health Board, Manukau City, New Zealand
  3. 3
    Institute of Environmental Science and Research Ltd, Porirua, New Zealand
  1. Professor Diana R Lennon, Department of Paediatrics, University of Auckland, Private Bag 92019, Auckland, New Zealand; d.lennon{at}


Background: Rheumatic fever is a preventable chronic disease preceded by group A β-haemolytic streptococcal (GABHS) pharyngitis.

Objective: To test the non-inferiority of once-daily (QD) oral amoxicillin to the recommended twice-daily (BID) oral penicillin V in GABHS pharyngitis.

Methods: This was a randomised non-inferiority trial carried out in a school-based clinic in New Zealand. Children presenting with GABHS pharyngitis were randomised to oral amoxicillin 1500 mg QD (or 750 mg if bodyweight was ⩽30 kg) or to oral penicillin V 500 mg BID (or 250 mg if bodyweight was ⩽20 kg) for 10 days. Observed medication and weekend diary cards were used to monitor adherence.

Outcome: Eradication of GABHS, determined with follow-up throat cultures on days 3–6, 12–16 and 26–36. GABHS isolates were serotyped to distinguish bacteriological treatment failures (and relapses) from new acquisitions. Non-inferiority was defined as an upper 95% confidence limit (CL) for the difference in success of eradication in the amoxicillin and penicillin V treatment groups of ⩽10%.

Results: 353 children with positive throat swabs for GABHS were randomised to amoxicillin (n = 177) or penicillin V (n = 176). The upper 95% CL for the differences in positive cultures between the antibiotics was 4.9% at days 3–6, 6.5% at days 12–16 and 8.5% at days 26–36. Treatment failures (including relapses) occurred at each visit in 5.8%, 12.7% and 10.7% of amoxicillin recipients and 6.2%, 11.9% and 11.3% of penicillin V recipients, respectively. No significant differences in resolution of symptoms were noted between treatment groups. One case of unsubstantiated acute rheumatic fever occurred after 7 days of amoxicillin.

Conclusion: In this adequately powered study, once-daily oral amoxicillin is not inferior to twice-daily penicillin V for the treatment and eradication of GABHS in children with pharyngitis.

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  • Funding: This study was funded by the New Zealand Heart Foundation, who had no role in the study design, the collection, analysis and interpretation of data, the writing of the report or the decision to submit the paper for publication.

  • Competing interests: None.