Among Dutch children with tympanostomy tubes who developed acute otorrhea, eardrops containing an antibiotic and glucocorticoid were more effective than oral antibiotics and much more effective than observation only at clearing the otorrhea in an open-label clinical trial, investigators reported online Feb. 19 in the New England Journal of Medicine.
In addition, the median duration of that episode of otorrhea was shorter, the median number of days with otorrhea during the next 6 months was much lower, and the median number of recurrences of otorrhea during the next 6 months was smaller with the eardrops. Disease-specific and health-related quality of life scores also "consistently favored eardrops," reported Dr. Thijs M.A. van Dongen of the epidemiology department, Julius Center for Health Sciences and Primary Care, University of Utrecht (the Netherlands) Medical Center, and his associates.
The findings suggest that observation only "may not be an adequate management strategy in such children," they noted.
The eardrops used in this study (Bacicoline-B, manufactured by Daleco Pharma) contain hydrocortisone, bacitracin, and colistin, and are active against most bacteria that cause acute tympanostomy-tube otorrhea, such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa. But the eardrops "are not routinely available outside the Netherlands and France."
Although there is no evidence yet to support this opinion, "we believe that any combination of antibiotic-glucocorticoid eardrops with similar antimicrobial activity, such as ciprofloxacin and dexamethasone, would be likely to have similar results," Dr. van Dongen and his colleagues wrote.
The researchers compared the three management strategies during a 3-year period in 230 children aged 1-10 years who were referred to the trial by ear, nose, and throat surgeons and family physicians. The mean age of the participants was 4.5 years, and the median duration of otorrhea before entry into the study was 3 days.
The children were randomly assigned to receive either five eardrops three times per day for 1 week in the discharging ear or ears (76 patients), oral amoxicillin-clavulanate suspension divided into three daily doses for 1 week (77 patients), or observation only for 2 weeks (77 patients). The children in group 2 received the dose recommended in the Netherlands and other countries in Europe, where resistance rates are low: 30 mg of amoxicillin and 7.5 mg of clavulanate per kilogram per day.
The first follow-up visit was scheduled at 2 weeks, with a final follow-up for complications and ear-related symptoms at 6 months.
The primary outcome measure – treatment failure, defined as the presence of otorrhea in one or both ears at 2 weeks – occurred in 5% of the eardrop group, 44% of the oral antibiotic group, and 55% of the observation-only group, the investigators said (N. Engl. J. Med. 2014;370:723-33).
The median duration of the index episode of otorrhea was 4 days for children who received eardrops, 5 days for those who received oral antibiotics, and 12 days for those assigned to observation only.
The median number of days with otorrhea during follow-up was 5 days for the eardrop group, 13.5 days for the oral antibiotic group, and 18 days for the observation-only group. Children treated with eardrops had no recurrences of otorrhea during follow-up; children in the other two groups had a median of 1 recurrence each within that 6-month period.
Scores on measures of disease-specific health-related quality of life improved slightly but significantly in the eardrop group, compared with the other study groups.
No serious complications of otitis media occurred, such as local cellulitis, perichondritis, mastoiditis, or intracranial abnormalities. Eighteen children who received oral antibiotics (23% of that group) developed gastrointestinal symptoms, and 3 (4%) developed rash.
The investigators noted that when designing this trial, they assumed that an absolute reduction of 20 percentage points in the incidence of otorrhea at 2 weeks would be necessary to show that one of the management strategies was superior to the others in a clinically relevant way. In the event, the reduction in risk was actually twice as large, "showing the importance of our findings for clinical practice," they said.
Dr. van Dongen and his associates added, "We believe our findings are applicable to children with uncomplicated acute tympanostomy-tube otorrhea presenting in either primary or secondary care."
This study was supported by the Netherlands Organization for Health Research and Development. Dr. van Dongen reported no financial conflicts of interest; one of his associates reported receiving grants from GlaxoSmithKline.