title: 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.
abstract: 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.
authors.affiliation: Children's Hospital, Bangkok, Thailand.
authors.forename: L
authors.initials: L
authors.lastname: Damrikarnlert
authors.forename: A C
authors.initials: AC
authors.lastname: Jauregui
authors.forename: M
authors.initials: M
authors.lastname: Kzadri
mesh_terms: D000208:Acute Disease; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage* / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010033:Otitis Media / Q000188:drug therapy*; D010349:Patient Compliance; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D019980:Amoxicillin-Potassium Clavulanate Combination