Dr. Tähtinen and her associates reported that a significantly lower rate of treatment failures occurred in children who received amoxicillin-clavulanate, compared with those who received placebo (18.6% vs. 44.9%, respectively). The difference in treatment failures was already apparent on day 3 in 13.7% of children who received amoxicillin-clavulanate, compared with 25.3% of those who received placebo. They also reported that overall, amoxicillin-clavulanate reduced the progression to treatment failure by 62% (hazard ratio 0.38) and the need for rescue treatment by 81% (HR 0.19).
In terms of side effects, the prevalence of diarrhea and eczema in the amoxicillin-clavulanate group was 47.8% and 8.7%, respectively, which was statistically higher than the rates in the placebo group (26.6% vs. 3.2%).
Going forward, they hypothesized, the identification of prognostic markers, “together with the use of stringent diagnostic criteria, could reduce the use of antimicrobial agents in the treatment of acute otitis media. Reduced use of antimicrobial agents may limit the development of resistant bacteria and increase the chances that the subsequent use of antimicrobial agents, when truly indicated, would be beneficial.”
Dr. Klein noted in his editorial that since physicians “cannot determine at the onset of the illness which child is likely to benefit from antimicrobial therapy, we need to consider these data as applicable to all young children in whom a certain diagnosis of acute otitis media has been made. Is acute otitis media a treatable disease? The investigators in Pittsburgh and Turku have provided the best data yet to answer the question, and the answer is yes; more young children with a certain diagnosis of acute otitis media recover more quickly with an appropriate antimicrobial agent.”
Dr. Hoberman disclosed that he has received honoraria and travel expense reimbursement from GlaxoSmithKline. One of the other study authors, Dr. Ellen R. Wald, disclosed that she has received grant support from Merck and GlaxoSmithKline. Dr. Jack Paradise disclosed that he received a consulting fee from University of Pittsburgh Medical Center. The study was supported by a grant from the National Institute of Allergy and Infectious Diseases.
The Turku study was supported by the Fellowship Award of the European Society for Pediatric Infectious Diseases. It also was supported by grants from the Foundation for Pediatric Research; Research Funds from Specified Government Transfers; the Jenny and Antti Wihuri Foundation; the Paulo Foundation; the Maud Kuistila Memorial Foundation; the Emil Aaltonen Foundation; the Finnish Cultural Foundation, Varsinais-Suomi Regional Fund; the Turku University Hospital Research Foundation; and the Finnish–Norwegian Medical Foundation. One of the other study authors, Dr. Aino Ruohola, disclosed that he received support for the travel to meetings for the study or other purposes from the Finnish Society of Infectious Disease Specialists, and that Inverness Medical Point of Care Diagnostics, Binax Inc. donated Binax NOW Streptococcus pneumoniae test for the study project. Dr. Olli Ruuskanen disclosed that he had been a consultant for Abbott and Novartis.
Dr. Klein disclosed that he received honoraria from Innovia Medical from 2005 to 2008.
View on the News
Trials Are Well Designed
Prior clinical studies have compared the outcome of AOM treated with antibiotics to that with placebo and have in general reported a more rapid resolution of signs and/or symptoms of AOM in the antibiotic-treated cohort. What is new?
First, both studies employed stringent criteria for entry ensuring that most, if not all, had AOM. Second, the choice and dose of amoxicillin-clavulanate provided coverage based on pharmacokinetic-pharmacodynamic principles for the majority of pneumococcal and Haemophilus isolates in each community. Thirdly, the study protocol provided for a sufficient frequency of follow-up to address the primary outcome (time to resolution in Pittsburgh and time to treatment failure in Turku). The results, a high rate of treatment failure in the placebo groups in both studies, distinguish these trials from several recent clinical trials and detail the potential advantages of effective antimicrobial therapy on the resolution of signs and symptoms.
Will these results change our approach to young children with AOM? As most episodes are currently treated with antibiotics, presumably these results will reinforce that approach. But these results also should challenge clinicians to further develop their diagnostic approach to AOM with greater emphasis on physical exam and to emphasize close follow-up for children who are initially managed with symptomatic care only.
DR. STEPHEN I. PELTON is with the division of pediatric infectious diseases at Boston Medical Center. He said he had no relevant financial disclosures.
