Ear Tubes: Drops More Effective Than Oral Antibiotics

Larry Hand

February 20, 2014

Treating children with tympanostomy tubes and otorrhea with antibiotic-glucocorticoid eardrops led to a −39 percentage point (95% confidence interval [CI], −51 to −26 percentage points) risk difference for otorrhea at 2 weeks compared with treating children with oral antibiotics, according to results of a study published in the February 20 issue of the New England Journal of Medicine.

Thijs M. A. van Dongen, MD, from the Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands, and colleagues conducted an open-label pragmatic trial in which 230 children aged 1 to 10 years were randomly assigned to receive either hydrocortisone-bacitracin-colistin eardrops (n = 76) or oral amoxicillin-clavulanate suspension (n = 77) or to undergo observation (n = 77).

At 2 weeks after first treatment, only 5% of children treated with the topical antibiotics still had otorrhea compared with 44% of children treated with oral antibiotics and 55% of children observed. That amounted to a −39 percentage point risk difference between the 2 forms of antibiotics (number needed to treat, 3), and a −49 percentage point (95% CI, −62 to −37 percentage points) risk difference between the eardrops and observation.

The median duration of initial otorrhea episodes came to 4 days for the topical antibiotics group, 5 days for the oral antibiotics group, and 12 days for the initial 2-week observation group (P < .001 for both comparisons). The total number of days with otorrhea came to 5 for the topical group, 13.5 for the oral group, and 18 for the observation group during 6 months of follow-up (P < .001 both comparisons).

Children experienced only mild treatment-related adverse events and no complications of otitis media.

Stopped Early

Originally aiming for an enrollment of 315 children, researchers stopped recruiting at 230 participants on the recommendation of an independent data review committee that was blinded to the group assignments. An interim analysis showed that the smallest risk difference was −32 percentage points (95% confidence interval, −48 to −17 percentage points; P < .001), which was greater than the predetermined primary end point of a risk difference of −20 percentage points.

From June 2009 through May 2012, researchers recruited children presenting with symptoms of tympanostomy-tube otorrhea lasting up to 7 days. At home visits, physicians obtained parental consent, confirmed the diagnosis otoscopically, took otorrhea culture samples, and collected disease-specific and demographic data. An independent data manager handled the randomization, and physicians were blinded to study groups.

Study physicians did not clear the children's ears during baseline or follow-up visits, but they instructed parents of children receiving topical antibiotics to clean easily removable discharge before applying ear drops. The parents kept daily diaries for treatment adherence, adverse events, and complications, which they shared with the study physician on a visit at 2-week and 6-month intervals.

Dosing amounted to 5 drops, 3 times daily for 7 days for the topical treatment, and 30 mg amoxicillin and 7.5 mg clavulanate per kilogram of body weight per day, 3 times daily, for 7 days. Children assigned to an initial 2 weeks of observation did not receive prescriptions.

Best Evidence Yet

The results of the trial provide "the best evidence so far to reinforce current guidelines in the United States that state if kids get ear infections with ear tubes in place, we should treat them with topical drops instead of oral antibiotics. And that has a lot of implications as far as limiting side effects, including bacterial resistance," Richard M. Rosenfeld, MD, MPH, professor and chair of otolaryngology at the State University of New York Downstate Medical Center in Brooklyn, New York, told Medscape Medical News.

Dr. Rosenfeld was lead author of clinical guidelines published in July 2013 for using tympanostomy tubes for treating children aged 6 months to 12 years.

The American Academy of Otolaryngology issued the guidelines on the basis of results of 3 randomized controlled trials. The academy also made their second Choosing Wisely recommendation to use topical instead of oral antibiotics.

"This new study is a much larger study with a lot of methodologic rigor that's done in an extremely well way that, I think, makes it incontrovertible at this point that the topical drops are really the way to go," Dr. Rosenfeld said. The study results present "a big quality improvement opportunity that's currently not being taken advantage of the way it should be in the United States."

Physicians place about 670,000 tubes a year in children's ears, Dr. Rosenfeld explained. "Of those, about 25% or more are going to develop [acute otorrhea]," which means that if an estimated 30% to 40% of these 167,500 children are prescribed oral antibiotics, 50,0000 to 60,000 will be taking unnecessary oral antibiotics a year.

The main problem, he said, is antibiotic resistance. Although oral antibiotics are the main driver of resistance globally, topical antibiotics do not promote resistance, essentially because they have about a 1000-fold higher concentration.

"Atomic Bomb"

"If you drop an atomic bomb on these bacteria, nothing lives. There's nothing left to be resistant. When you tickle them with a little bit of oral that trickles its way up to the site of the infection through your blood, the weak ones go, but the intermediate and strong ones survive and you promote resistance. There's no evidence of resistance being promoted from topical drops," he explained.

He said a big strength of the new study is the magnitude of difference between topical and oral treatments, especially the finding that the number to treat to prevent an additional bad outcome came to 3. "This is about as big as it gets for effects size in medicine," he said.

Another pragmatic issue is time. Citing the daily results of the article, Dr. Rosenfeld explained, "After 2 days, there's no difference, but 4 days in, you've already seen a dramatic drop in the group that gets the eardrop. If the goal of the parent is to get the child back to school, day care, or playgroups more quickly, you're going to get your child back to their activities a lot quicker if you dry up the ear with the topical drops."

This research was supported by the Netherlands Organization for Health Research and Development. One coauthor has reported receiving grant support through her institution from GlaxoSmithKline. The other authors and Dr. Rosenfeld have disclosed no relevant financial relationships.

N Engl J Med. 2014;370:723-733. Abstract


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