Objective:

This phase 2/3, open-label, noncomparative, multi-centre study, assessed the efficacy of once daily CEF in the treatment of children with AOM at risk of PROM.

Methods:

Children aged 6 months to 4 years with signs/symptoms of AOM at risk of PROM (characterised by >=2 of the following: antibiotics in previous 3 months, age <=2 years, day-care attendance or siblings/household contacts age <=8 years), diagnosed by pneumatic otoscopy and tympanocentesis, received once daily CEF for 10 days. Children were evaluated pretreatment (Day 1), on therapy (Days 4–6), end of therapy (Days 12–14) and follow-up (Days 25–28). Repeat tympanocentesis on Days 4–6 was used to assess bacteriologic response.

Results:

A total of 447 children were enrolled in the US, Israel and Latin America. Fifty-seven percent were male, 64% were <=2 years of age. For the 227 children clinically and bacteriologically evaluable, 58% were male and 74% were <=2 years of age; 13% had received pneumococcal conjugated vaccine. Forty-two percent of these children had >=3 AOM infections within the past 12 months (including present infection) and 56% had received treatment for AOM within previous 3 months. Fifteen percent had multiple pathogens isolated pretreatment. Forty-seven percent of S. pneumoniae isolates were penicillin non-susceptible (PNSP). Bacteriologic eradication on Days 4-6 was achieved in 159/226 (70%) children and 188/262 (72%) of all pathogens were eradicated. Bacteriologic response in children with a single pathogen was 148/193 (77%). Eradication of penicillin susceptible, intermediate and resistant S. pneumoniae was 84% (46/55), 65% (17/26) and 39% (9/23), respectively; eradication of H. influenzae was 84/123 (68%). Overall clinical response for clinically and bacteriologically evaluable children on Days 12–14 was 82% and for S. pneumoniae and H. influenzae it was 75 and 82%, respectively. Clinical response on Days 25–28 was 142/167 (85%). Clinical response for children with pretreatment negative and positive cultures was 97 and 82%, respectively. CEF was discontinued due to an adverse event in only 3% of children. The most common adverse events were diarrhoea (13%) and vomiting (7%), most of mild severity.

Conclusions:

This study specifically evaluated children with AOM at risk for PROM. In this high-risk population, CEF demonstrated good activity against penicillin susceptible S. pneumoniae, but decreased activity against PNSP, and a moderate effect against other pathogens. Further studies are needed to evaluate modified dosing or formulations of CEF in this high-risk population.