Multicenter controlled trial comparing ceftibuten with amoxillin/clavulanate in the empiric treatment of acute otitis media

The efficacy and safety of ceftibuten (9 mg/kg daily for 10 days) were compared with those of amoxicillin/clavulanate (Augmentin® 40 mg/kg/day given every 8 hours for 10 days) in the empiric treatment of acute otitis media in children. This was a multicenter, investigator-blinded study with 1 :1 randomization. Overall clinical response and signs and symptoms of otitis were collected prospectively pretreatment, 3 to 5 days during treatment, 1 to 3 days posttreatment and at 2- to 4-week follow-up. In addition to spontaneous reports of other adverse events, gastrointestinal adverse events were prospectively elicited at each visit. Two hundred ninety-six patients (146 ceftibuten and 150 amoxicillin/clavulanate) were treated with at least 1 dose of study medication. Compliance with dosing was assessable with weight of drug consumed in 127 patients in each treatment group. Five percent (6 of 127) of ceftibuten patients and 11% (14 of 127) of amoxicillin/clavulanate patients received <80% of prescribed drug (P = 0.10) and were therefore not valid. Two hundred twenty-two patients (121 ceftibuten and 101 amoxicillin/clavulanate) received a minimum of 80% of prescribed medication and were compliant with the protocol. Ceftibuten and amoxicillin/clavulanate groups were comparable both for demographic variables and for baseline signs and symptoms. Clinical success (cure/improvement) at 1 to 3 days posttreatment was seen in 93% (113 of 121) of ceftibuten-treated patients and 97% (95 of 98) of amoxicillin/clavulanate-treated patients (P = 0.10). Clinical relapse was seen in 13% (15 of 112) of ceftibuten-treated patients and 15% (14 of 93) of amoxicillin/clavulanate-treated patients (P = 0.60). Improvement in individual signs and symptoms confirm overall clinical success. No difference in resolution of middle ear effusion, based on improvement in tympanic membrane mobility or resolution of air/fluid level, was observed between ceftibuten and amoxicillin/clavulanate. Adverse events, both spontaneous and elicited, were reported more frequently with amoxicillin/clavulanate (67% (100 of 150)) than with ceftibuten (42% (61 of 146)). This difference is primarily caused by diarrhea and the related event, diaper rash. Treatment-related diarrhea occurred in 34% (51 of 150) of amoxicillin/clavulanate patients and 9% (13 of 146) of ceftibuten patients and diaper rash occurred in 17% (25 of 150) of amoxicillin/clavulanate patients and 3% (5 of 146) of ceftibuten patients. Only 3 severe adverse events occurred ; each one was diarrhea in an amoxicillin/clavulanate patient. No cases of persistent diarrhea requiring Clostridium difficile testing were reported.