Clinical Context

Acute otitis media (AOM) remains a common infection among children, and it may rarely lead to serious health consequences. The latest recommendations regarding the management of AOM among children from the American Academy of Pediatrics (AAP) were published in the journal Pediatrics^[1] in March 2013.

One of the most controversial issues in the management of pediatric AOM is the use of antibiotics. The recommendations advocate for antibiotic treatment among children between ages 6 and 23 months with AOM who have symptoms of ear pain for at least 48 hours or a temperature of 39°C or higher. Children in this age group with bilateral AOM should be treated with antibiotics regardless of their symptoms.

However, even among these young children, antibiotics for AOM may be withheld if no severe symptoms are present, and a mechanism is in place to reevaluate the child and start antibiotics if there is no improvement in symptoms or if symptoms worsen within 48 to 72 hours. This same rule generally applies for children at age 24 months and older.

Amoxicillin was considered the treatment of choice for AOM in the AAP recommendations. However, the question of the duration of treatment with antibiotics for AOM among children has been controversial. The current study by Hoberman and colleagues addresses this issue with results from a new randomized trial.

Study Synopsis and Perspective

A 10-day course of antibiotics worked better than a 5-day course for young children with ear infections in a randomized controlled trial of 520 children at 2 centers. The 5-day course did not result in any fewer cases of antibiotic-resistant infections or adverse events.

Alejandro Hoberman, MD, from the Department of Pediatrics at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, and colleagues report their findings in an article published in the December 22 issue of the New England Journal of Medicine.^[2]

"For now, 10 days of amoxicillin-clavulanate for children younger than 2 years of age who have a definite diagnosis of [AOM] seems to be a reasonable option," Margaret A. Kenna, MD, MPH, from the Department of Otolaryngology and Communication Enhancement and Boston Children's Hospital, Boston, Massachusetts, writes in an accompanying editorial.^[3]

The trial enrolled children between 6 and 23 months old -- the most likely age group to have treatment failure and recurrence. To be enrolled, the children had to have a diagnosis of AOM based on 3 criteria: the presence of middle ear effusion, moderate or marked bulging of the tympanic membrane or slight bulging along with pain or redness, and a recent score of 3 or more on the 14-point Acute Otitis Media-Severity of Symptoms scale. Tugging of ears, crying, irritability, difficulty sleeping, diminished activity, diminished appetite, and fever are the criteria on that scale. All children had had at least 2 doses of pneumococcal conjugate vaccine.

Families were given 2 bottles of medicine: one of amoxicillin and clavulanate (90 and 6.4 mg/kg body weight) for the first 5 days and a second bottle containing either the same medicine or a placebo of the same color, texture, odor, and taste.

The investigators followed up with the child's family twice in the next 2 weeks and saw the child for visits every 6 weeks through the rest of the respiratory infection season. Whenever a child contracted another ear infection, he or she was treated with the same regimen as before (either 5 or 10 days). After 2 recurrences, however, or any time treatment failed, the child was given a full 10-day dose of amoxicillin-clavulanate, ceftriaxone, or cefdinir.

Clinical failure was more common in the children receiving the 5-day course than in those receiving the 10-day course (34% vs 16%; difference of 17 percentage points; 95% confidence interval, 9-25 percentage points). To prevent 1 episode of clinical failure, the number needed to treat with a 10-day course is 6.

After the initial treatment, both groups of children had less penicillin-susceptible Streptococcus pneumoniae in their nasopharynx. Susceptible and nonsusceptible strains of Haemophilus influenzae remained the same. Adverse events were not significantly different between the groups.

Aside from treatment, children were more likely to have clinical failure if they spent more than 10 hours per week with at least 3 other children (P =.02) and if they initially presented with infections in both ears (P <.001).

The authors note that the results cannot be generalized to children older than the children in this study.

Dr Kenna, who was not involved in the study, notes that a Cochrane review on this topic found that some studies showed no difference between long and short courses of antibiotics. However, many of those studies were not blinded, did not use strict criteria for diagnosis or outcome measures, and did not directly compare the same drug in different durations.

Dr Hoberman and a coauthor have received consulting fees from Genocea Biosciences. Dr Hoberman also has received grant support from Ricoh Innovations and holding pending patents related to the development of a reduced clavulanate concentration version of amoxicillin-clavulanate potassium and the development of a method and apparatus for aiding in the diagnosis of otitis media by classifying tympanic membrane images. The remaining authors have disclosed no relevant financial relationships.

N Engl J Med. 2016;375:2446-2456, 2492-2493.

Clinical Implications

• Current recommendations state that children between 6 and 23 months old with severe symptoms of unilateral AOM or bilateral AOM with or without symptoms should receive antibiotics. Children in this age range without severe symptoms of unilateral AOM may be observed without antibiotics, as long as close follow-up can be arranged. Amoxicillin is the antibiotic of choice for AOM.
• The current study by Hoberman and colleagues demonstrates that a 5-day course of amoxicillin-clavulanate is associated with a higher risk for clinical failure vs a 10-day course among young children with AOM. There was no difference in the rates of middle ear effusion after treatment, recurrence of AOM, or colonization with resistant bacteria in comparing the 5-day vs the 10-day treatment group.
• Implications for the Healthcare Team: The natural inclination of clinicians is to give the shortest course of treatment needed to reduce patients' symptoms and improve prognosis. In AOM among young children, the healthcare team should advise patients that a longer course of antibiotics may be more beneficial.

CME Test