Equivalent efficacy and reduced occurrence of diarrhea from a new formulation of amoxicillin/clavulanate potassium (Augmentin®) for treatment of acute otitis media in children

OBJECTIVE: To compare the safety and efficacy, in treating acute otitis media (AOM) in children, of a new formulation of amoxicillin/clavulanate potassium (Augmentin) oral suspension providing 45/6.4 mg/kg/day and administered twice daily (bid) for 5 and 10 days, respectively, with the safety and efficacy of the original formulation providing 40/10 mg/kg/day and administered three times daily (tid) for 10 days. STUDY DESIGN: Eight hundred sixty-eight children ages 2 months to 12 years with AOM were randomly assigned to one of the three treatment groups. Stringent criteria were used for the diagnosis of AOM and for determinations of "cure" and "improvement." Subjects were reexamined on Days 12 to 14 and 32 to 38. RESULTS: Among subjects whose treatment and follow-up conformed fully to protocol, the proportion of treatment successes (clinically cured or improved) on Days 12 to 14 was 78.8% (149 of 189) in the tid 10-day group, 86.5% (154 of 178) in the bid 10-day group and 71.1% (140 of 197) in the bid 5-day group. Corresponding values on Days 32 to 38 were 64.2% (95 of 148) in the tid 10-day group, 63.1% (94 of 149) in the bid 10-day group and 57.8% (93 of 161) in the bid 5-day group. None of the differences between the tid 10-day regimen and either of the 2 bid regimens were statistically significant, but the bid 10-day regimen was significantly more effective than the bid 5-day regimen in younger subjects. In the study population as a whole, results were similar to those in per protocol subjects. Overall the incidence of protocol-defined diarrhea was 26.7% (74 of 277) in the tid 10-day group, compared with 9.6% (27 of 280) in the bid 10-day group (P < 0.0001) and 8.7% (25 of 286) in the bid 5-day group (P < 0.0001). CONCLUSIONS: In comparison with the original formulation of Augmentin administered tid for 10 days in the treatment of AOM in children, the new formulation administered bid for 10 days provides at least equivalent efficacy and causes substantially less diarrhea. Administration for 5 days appears not to provide equivalent efficacy, but the difference appears limited to younger children and the margin of difference is small.