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Treatment of Streptococcal Pharyngitis With Once-Daily Compared With Twice-Daily Amoxicillin: A Noninferiority Trial

Clegg, Herbert W. MD*; Ryan, Amy G. MD*; Dallas, Steven D. PhD; Kaplan, Edward L. MD; Johnson, Dwight R. BS; Norton, H James PhD§; Roddey, Oliver F. MD*; Martin, Edward S. MD*; Swetenburg, Raymond L. MD*; Koonce, Elizabeth W. MD*; Felkner, Mary M. MD*; Giftos, P Michael MD*

The Pediatric Infectious Disease Journal: September 2006 - Volume 25 - Issue 9 - p 761-767
doi: 10.1097/01.inf.0000235678.46805.92
Original Studies

Background: Two relatively small previous studies comparing once-daily amoxicillin with conventional therapy for group A streptococcal (GAS) pharyngitis reported similar rates of bacteriologic success for each treatment group. The purpose of this study was to further evaluate once-daily amoxicillin for GAS pharyngitis in a larger study.

Methods: In a single pediatric practice, from October through May for 2 consecutive years (2001–2003), we recruited children 3 to 18 years of age who had symptoms and signs suggestive of GAS pharyngitis. Patients with a positive rapid test for GAS were stratified by weight (<40 kg or ≥40 kg) and then randomly assigned to receive once-daily (750 mg or 1000 mg) or twice-daily (2 doses of 375 mg or 500 mg) amoxicillin for 10 days. We determined bacteriologic failure rates for GAS in the pharynx from subsequent swabs taken at 14 to 21 (visit 2) and 28 to 35 (visit 3) days after treatment initiation. We conducted a randomized, controlled, investigator-blinded, noninferiority trial to evaluate whether amoxicillin given once daily would have a bacteriologic failure rate no worse than that of amoxicillin given twice daily within a prespecified margin of 10%. GAS isolates were characterized to distinguish bacteriologic failures from new acquisitions. Adverse events were described and adherence was evaluated by review of returned daily logs and dosage bottles.

Results: Of 2139 potential study patients during the 2-year period, we enrolled 652 patients, 326 into each treatment group. Children in the 2 groups were comparable with respect to all demographic and clinical characteristics except that children <40 kg more often presented with rash in each treatment group. At visit 2, failure rates were 20.1% (59 of 294) for the once-daily group and 15.5% (46 of 296) for the twice-daily group (difference, 4.53%; 90% confidence interval [CI], −0.6 to 9.7). At visit 3, failure rates were 2.8% (6 of 216) for the once-daily group and 7.1% (16 of 225) for the twice-daily group (difference, −4.33; 90% CI, −7.7 to −1.0). Gastrointestinal and other adverse events occurred in the once-daily treatment group with a frequency comparable to that in the twice-daily treatment group. Presumed allergic reactions occurred in 0.9% (6 of 635). More than 95% (516 of 541) of patients complied with 10 days of therapy with no significant differences between groups.

Conclusions: We conclude that amoxicillin given once daily is not inferior to amoxicillin given twice daily. Gastrointestinal and other events did not occur significantly more often in the once-daily treatment group. From the data in this large, investigator-blinded, controlled study, once-daily amoxicillin appears to be a suitable regimen for treatment of GAS pharyngitis.

From *Eastover Pediatrics, Charlotte, NC; †Presbyterian Laboratory Services, Microbiology Department, Presbyterian Hospital, Charlotte, NC; ‡World Health Organization Collaborating Center for Reference and Research on Streptococci, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN; and the §Department of Biostatistics, Carolinas Medical Center, Charlotte, NC.

Accepted for publication June 1, 2006.

This study was supported by grants from the American Academy of Pediatrics Research in Pediatric Practice Fund and from the Foundation for the Carolinas.

Address for correspondence: Herbert W. Clegg, MD, Eastover Pediatrics, 2600 E. 7th St., Charlotte, NC 28204. E-mail:

© 2006 Lippincott Williams & Wilkins, Inc.