By Philip R. Fischer, MD, DTM&H
Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN; Department of Pediatrics, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
SYNOPSIS: In a large U.S. population group, use of short-term oral azithromycin was associated with an increased risk of sensorineural hearing loss.
SOURCE: Dabekaussen KFAA, Andriotti T, Ye J, et al. Association of outpatient oral macrolide use with sensorineural hearing loss in children, adolescents, and young adults. JAMA Otolaryngol Head Neck Surg 2022; July 21. doi 10.1001/jamaoto.2022.1293. [Online ahead of print].
In the United States, azithromycin is prescribed more than any other outpatient antibiotic, accounting for more than 54,000,000 prescriptions per year. In fact, household surveys suggest that 0.6% of U.S. children have used azithromycin within the past week. Macrolides are broadly effective in the treatment of acute otitis media, community-acquired pneumonia, and sinusitis.
Clinicians often inform families about the risks of macrolides (abdominal discomfort in 15% to 20% of children on azithromycin, and a real but rare possibility of prolongation of the QT interval in the cardiac cycle). Some studies have identified a risk of sensorineural hearing loss when high doses of macrolides are used for prolonged periods in adults, but the risk of hearing loss with routine outpatient use of macrolides in children had not been evaluated.
In the United States, up to 19% of children have hearing loss, with more than half of these having “idiopathic” hearing loss. One might wonder if a commonly used medication might account for some of these cases of “idiopathic” hearing loss.
Thus, a study team from Boston used a U.S. military insurance database to evaluate the risk of hearing loss with short-term outpatient use of macrolides in children. With a case-control study, they compared 875 children and adolescents (mean age 5.7 years) identified to have sensorineural hearing loss with 875 age- and sex-matched “controls” without hearing loss. They carefully controlled for all potentially confounding variables.
Macrolides were used more commonly (70% vs. 62%) and penicillin-family antibiotics less commonly (30% vs. 38%) in children with hearing loss than in children without hearing loss. (The most common duration of macrolide use was five days in 79% of children who received a macrolide.) A multivariate analysis demonstrated a statistically significant odds ratio of 1.37 for developing hearing loss if a macrolide, rather than a penicillin, was used.
The authors acknowledged that the risk of an individual child using azithromycin developing sensorineural hearing loss still is very low. Nonetheless, a risk of even 0.7% considered over the millions of doses of azithromycin being prescribed still could account for hundreds of thousands of individuals losing hearing.
COMMENTARY
Azithromycin is very effective against the germs causing common childhood infections, such as otitis media and pneumonia. The medication’s convenient once-daily dosing and relatively mild gastrointestinal side effects make it a popular choice in treating children. However, these new data raise a “red flag” of the possibility that irreversible hearing loss is an uncommon but real complication of macrolide use in children.
In an editorial accompanying the Boston paper, potential mechanisms of macrolide ototoxicity were discussed.1 Human case studies, animal investigations, and in vitro research suggest that macrolides can alter potassium secretion in the stria vascularis in the cochlear duct.1
REFERENCE
- Lieu JEC, Rybak L. Possibility of macrolides causing hearing loss in children – what did you say? JAMA Otolaryngol Head Neck Surg 2022; July 21. doi 10.1001/jamaoto.2022.1292. [Online ahead of print].
