Children with a certain diagnosis of acute otitis media who were treated with amoxicillin-clavulanate recovered more quickly, compared with those who received placebo, results from two large, separate studies demonstrated.
The findings, conducted by researchers at the University of Pittsburgh and at the University of Turku, Finland, and which appear in the Jan. 13, 2011, edition of the New England Journal of Medicine, provide the strongest evidence to date supporting a regimen of antimicrobial therapy in children with a certain diagnosis of acute otitis media (AOM).
"A study with an appropriate design was needed to resolve the controversy regarding antimicrobial therapy versus observation in children with certain diagnoses of acute otitis media," Dr. Jerome O. Klein of the department of pediatrics at Boston University, wrote in an editorial about the studies (N. Engl. J. Med. 2011;364:168-9). "The investigators in both Pittsburgh and Turku have provided such a study. They performed randomized, blinded trials of the use of amoxicillin-clavulanate as compared with placebo in the age group at greatest risk."
In 2004, the American Academy of Pediatrics and the American Academy of Family Physicians issued a clinical practice guideline that endorsed initial observation as an option in children aged 6-23 months with mild otalgia and a temperature of less than 39°C in the last 24 hours, and in whom the diagnosis of AOM is uncertain (Pediatrics 2004;113:1451-65).
However, those recommendations were based on previous clinical trials that contained "substantial limitations," according to researchers from one of the studies, who were led by Dr. Alejandro Hoberman of the department of pediatrics at the University of Pittsburgh (N. Engl. J. Med. 2011;364:105-15).
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.* Moreover, rates of spontaneous improvement similar to the rates seen in those studies among children receiving placebo have not been found uniformly. Therefore, for children with acute otitis media, the circumstances in which immediate antimicrobial treatment is the preferred strategy have remained unclear," they said.
Dr. Hoberman and his associates randomized 291 children aged 6-23 months who were diagnosed with AOM to receive amoxicillin-clavulanate or placebo for 10 days. To meet eligibility for the trial, the children were required to have received at least two doses of pneumococcal conjugate vaccine and to have AOM that was diagnosed based on all three criteria: onset of symptoms within 48 hours that parents rated with a score of at least 3 on the Acute Otitis Media Severity of Symptoms (AOM-SOS) scale; the presence of middle-ear effusion; and moderate or marked bulging of the tympanic membrane or slight bulging accompanied by either otalgia or marked erythema of the membrane.*
A significantly higher proportion of children who received amoxicillin-clavulanate had initial clearance within 7 days, compared with their counterparts in the placebo group (35% vs. 28%, respectively by day 2; 61% vs. 54% by day 4; and 80% vs. 74% by day 7). A similar relationship was seen in terms of sustained resolution of symptoms (20% vs. 14% by day 2; 41% vs. 36% by day 4; and 67% vs. 53% by day 7).
The rate of clinical failure, which was defined as the persistence of signs of acute infection on otoscopic evaluation, was less likely in the children who received amoxicillin-clavulanate, compared with those who received placebo (4% vs. 23%, respectively, at or before the visit on day 4 or 5; and 16% vs. 51% at or before the visit on days 10-12).
Dr. Hoberman and his associates concluded that treatment with amoxicillin-clavulanate for 10 days in children aged 6-23 months with AOM "affords a measurable short-term benefit, irrespective of the apparent severity of the illness. The benefit must be weighed against concern not only about the side effects of the medication but also about the contribution of antimicrobial treatment to the emergence of bacterial resistance. These considerations underscore the need to restrict treatment to children whose illness is diagnosed with the use of stringent criteria."
Researchers from Finland reported similar findings. With equally strict eligibility criteria, Dr. Paula Tähtinen and her associates at Turku University Hospital randomized 319 children aged 6-35 months who were diagnosed with AOM to receive amoxicillin-clavulanate or placebo for 7 days (N. Engl. J. Med. 2011;364:116-26).