Equivalent efficacy and reduced occurrence of diarrhea from a new formulation of amoxicillin/clavulanate potassium (Augmentin) for treatment of acute otitis media in children. Efficacy and safety of amoxycillin/clavulanate (Augmentin) twice daily versus three times daily in the treatment of acute otitis media in children. The Augmentin 454 Study Group. Is treatment of acute otitis media with once-a-day amoxicillin feasible? Results of a pilot study. Amoxicillin twice daily in the treatment of acute otitis media in infants and children. Efficacy of twice-daily dosing of amoxycillin/clavulanate in acute otitis media in children.
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.
                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.
                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).
                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. This multicenter, randomized, single-blind study compared the efficacy and safety of a new, twice-daily formulation of amoxycillin/clavulanate (Augmenting) with the standard three-times-daily formulation. Children with a clinical diagnosis of acute otitis media, aged between 2 months and 12 years, received either amoxycillin/clavulanate 45/6.4 mg/kg/day twice-daily (b.d.) (range 38.3/5.5-76.2/10.9 mg/kg/day) or amoxycillin/clavulanate 40/10 mg/kg/day three-times-daily (t.d.s.) (range 25/6.25-56/14 mg/kg/day) for 7 or 10 days. Patients were evaluated during therapy (Days 3-5), at the end of therapy (Days 7-12) and at follow-up (Days 38-42). At the end of therapy, for the intent-to-treat and per-protocol populations, respectively, clinical success (cure) was achieved by approximately 94% of patients in both treatment groups. A successful bacteriological response at the end of therapy (Visit 3) was documented in 7/9 patients (77.8%) in the twice-daily group and in 11/13 patients (84.6%) in the three-times-daily group. At follow-up (Visit 4), 93.3% of patients in the twice-daily group and 87.9% in the three-times-daily group continued to have a clinically successful response. Both treatment regimens were well tolerated, with most adverse events being of a mild-moderate and transient nature. The most common treatment-related adverse event was diarrhea, occurring in 7.2% of patients in the twice-daily group and in 10.7% of the three-times-daily group. In total, 173 patients (82.8%) in the twice-daily group and 151 patients (73.3%) in the three-times-daily group were compliant with medication. In conclusion, this study confirms that b.d. amoxycillin/clavulanate is an effective treatment for pediatric acute otitis media and demonstrates that the b.d. and t.d.s. formulations of amoxycillin/clavulanate produce equivalent efficacy. Furthermore, there was a trend towards a higher level of compliance and a lower incidence of drug-related adverse events in the twice-daily compared with the three-times-daily treatment group. We report a study of the feasibility of once-a-day amoxicillin to treat acute otitis media (AOM). Seventy-seven children between ages 7 months and 12 years with AOM participated in a double-blind, placebo-controlled trial. Subjects received amoxicillin 40 mg/kg/day for 10 days. They were similar in age, sex, history of ear infections, and presenting symptoms. Group I received one total dose of amoxicillin and two doses of placebo daily. Group II received three divided doses of amoxicillin daily. Parents kept a daily diary of symptoms related to the child's illness and possible medication side effects. Ten children were lost to follow-up. In the remaining 67, pneumatic otoscopy and tympanometry after 10 to 14 days revealed that AOM had resolved in 82% of group I and 68% of group II. Groups showed no significant differences in persistence of middle ear effusion; 39% in group I and 24% in group II still had fluid. Diaries showed no significant differences between groups in medication side effects. Thus, reduced-frequency dosing for AOM seems feasible and more realistic than current regimens. A total of 110 children with acute otitis media were assigned randomly to treatment with 60 mg/kg per day amoxicillin in a twice-daily (group A) or a thrice-daily (group B) regimen for 10 days. Patients were scheduled for follow-up examinations at mid-treatment, 5 days after the end of therapy and 30, 60, 90 days after starting therapy. At 15 days 6 out of 55 patients (10.9%) treated with amoxicillin twice daily were considered treatment failures compared to 4 children (7.2%) in the thrice daily group. Rates of cure, recurrent otitis media and persistent middle ear effusion were comparable in the two groups of patients at later time intervals. By 90 days the total cure rate was 42.3% (22/52) in children treated twice daily and 41.5% (22/53) in those who had received amoxicillin thrice daily. At the same time persistence of bilateral and unilateral effusion was noted in 12/52 (23.1%) and 8/52 (15.3%) children in group A and in 16/53 (30.1%) and in 10/53 (18.9%) in group B respectively. No significant difference was noted in the two treatment regimens with regard to adverse side effects. Because reduction in division of the amoxicillin dose caused no significant difference in the efficacy of antibiotic treatment of acute otitis media in infants and children, we think that this simplified scheme of therapy can routinely be used in clinical practice and thus improve compliance to antibiotic administration. Children with acute otitis media (AOM), aged 2-12 years, were randomised to 10 days treatment with amoxycillin/clavulanate (A/C) 70/10 mg/kg/day given b.i.d. (231 patients) or to A/C 60/15 mg/kg/day given t.i.d. (232 patients). Clinical success rates at end of therapy (10-17 days) were 91.8% for the b.i.d. group and 90.5% for the t.i.d. group and at follow-up (28-42 days) were 80.1% for the b.i.d. group and 77.6% for the t.i.d. group, indicating that the b.i.d. regimen was as effective as the t.i.d. regimen. There was no statistically significant difference in incidence of adverse experiences between the two groups. The overall incidence of protocol defined diarrhoea assessed from diary booklets was low, with a lower incidence in the b.i.d. group (6.7%) than in the t.i.d. group (10.3%). Significantly more patients in the b.i.d. group (83.1%) than in the t.i.d. group (72.8%) had at least 80% compliance over a 7-10 day treatment period. A/C given twice or three-times daily was highly effective in the treatment of AOM in children. The two regimens showed equivalent clinical efficacy, both were well tolerated, and there was evidence of improved compliance with the b.i.d. regimen.
This review showed insufficient evidence to judge whether once or twice daily doses of amoxicillin, with or without clavulanate, were comparable with three or four daily doses for the treatment of AOM. The evidence appears to be biased and therefore no firm conclusions can be drawn.