Overall, 47% of children given antibiotics developed asymptomatic middle ear effusion -- defined as a type B tympanogram -- compared with 50.6% of placebo patients (relative risk 0.93, 95% CI 0.82 to 1.04, P=0.19), reported Maroeska Rovers, Ph.D., of University Medical Center Utrecht, and colleagues, in the February issue of Archives of Otolaryngology -- Head and Neck Surgery.
The largest -- but nonsignificant -- beneficial effect from antibiotics was found in the subgroup of children two and older who did not have recurrent acute otitis media (35.7% of placebo patients and 24.3% of those receiving antibiotics developed effusion at one month, RR 0.68, 95% CI 0.34 to 1.02, P=0.44).
"Because of this marginal effect and the known negative effects of prescribing antibiotics, including the development of antibiotic resistance and adverse effects, we do not recommend prescribing antibiotics to prevent [middle ear effusion]," Dr. Rovers and colleagues wrote. This is in agreement with current guidelines.
They performed a literature search for randomized trials that studied children no older than 12 with acute otitis media. The studies had to compare antibiotic therapy with placebo or no antibiotics. All were required to have measured middle ear effusion at one month, the primary outcome for the meta-analysis.
The researchers identified 19 trials but 13 were excluded because of inadequate randomization or the use of antibiotics in the control arm. Data from another trial were unavailable, leaving five for the final analysis.
Amoxicillin was the antibiotic used in each of the five trials (amoxicillin-clavulanate in one). Amoxicillin was compared with placebo in four and delayed treatment with the drug in one. Duration of treatment was seven or 10 days.
The meta-analysis included 1,328 children ages six months to 12 years who received antibiotics; 44% were younger than two, 50.2% were male, 51.8% had recurrent acute otitis media, 34.3% had bilateral acute otitis media, and 94.4% had a red tympanic membrane.
To assess independent predictors for developing asymptomatic middle ear effusion at one month absent antibiotic treatment, the researchers looked at the 660 children from the control arms of the trials. They identified two predictors, age younger than two (odds ratio 2.2, 95% CI 1.6 to 3.0) and recurrent acute otitis media (OR 1.5, 95% CI 1.1 to 2.1).
The highest absolute risk of asymptomatic middle ear effusion at one month was 64% (95% CI 58% to 70%) in children younger than two who had recurrent acute otitis media; the lowest was 30% (95% CI 25% to 35%) in children two or older without the recurrent condition.
Dr. Rovers and colleagues acknowledged that certain limitations of the meta-analysis should be considered. The primary outcome of asymptomatic middle ear effusion at one month was selected because it was the only time point that tympanograms were obtained in all available trials. With a longer study period they may have found a smaller antibiotic effect because of more spontaneous resolution, they said.
Also, use of a type B tympanogram to define the primary outcome may have caused some misclassification.
Furthermore, antibiotic treatment in the trials lasted either seven or 10 days, and longer treatment may have increased effectiveness.
Finally, the researchers did not study all possible subgroups. "Other subgroups that might benefit more from treatment using antibiotics (e.g., those with Down's syndrome or cleft palate) could not be studied in this [individual patient data] meta-analysis because these subgroups were excluded from the individual trials," they said.
"More research is need to identify relevant subgroups of children who have [middle ear effusion] that might benefit from other treatments," they concluded.
|The study was supported by the Dutch College of General Practitioners and a grant from the Netherlands Organization for Health Research and Development.
- Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine, Harvard Medical School, Boston
Archives of Otolaryngology -- Head and Neck SurgerySource Reference: Koopman L, et al "Antibiotic therapy to prevent the development of asymptomatic middle ear effusion in children with acute otitis media" Arch Otolaryngol Head Neck Surg 2008; 134: 128-132.