The main outcome of the study was time to treatment failure from the first dose until the end-of-treatment visit on day 8. Treatment failure was a composite outcome consisting of six components: no improvement in overall condition by the first scheduled visit (day 3); a worsening of the child’s condition at any time; no improvement in otoscopic signs by day 8; perforation of the tympanic membrane at any time; severe infection that required systemic open-label antimicrobial treatment at any time; or any other reason for discontinuing the study drug.
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 group (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.
* CORRECTION, 3/17/2011: The original version of this article omitted the word "few" from the following sentence: "These include the lack of stringent diagnostic criteria, the inclusion of very few young children, and the use of an antimicrobial drug that had limited efficacy or that was administered in suboptimal doses." An earlier version of this story also said that children were required to meet one of three criteria in order to participate in the trial; they were actually required to meet all criteria. This version has been corrected.