Oral macrolide exposure increases the risk for sensorineural hearing loss in children, adolescents, and young adults more than penicillin exposure, according to a case-control study published in JAMA Otolaryngology – Head and Neck Surgery.

Prior research has found an association between the sudden development of sensorineural hearing loss in adults with comorbid conditions following intravenous or high-dose macrolide therapy. However, the auditory effect of outpatient oral macrolide therapy in children is extremely limited. For this retrospective case-control study, researchers compared the auditory effect of oral outpatient macrolide vs penicillin therapy in pediatric patients.

The researchers conducted a case-control study using the United States military TRICARE database between October 1, 2009 and September 30, 2014 to gather data on outpatient children, adolescents, and young adults who received treatment with macrolides and a diagnosis of sensorineural hearing loss within a year of macrolide exposure. The experimental group consisted of 875 patients who received at least 1 dose of macrolides while the control group consisted of 875 patients who received penicillin prescriptions.

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Prescribed oral macrolides included erythromycin, azithromycin, clarithromycin, fidaxomicin, and telithromycin. The researchers compared the effect of macrolides on hearing versus the effect of the penicillin group on hearing. The penicillin group consisted of amoxicillin, amoxicillin-clavulanate, ampicillin, ampicillin-sulbactam, benzylpenicillin, carbenicillin indanyl sodium, cloxacillin, dicloxacillin, oxacillin, penicillin G potassium, and phenoxymethylpenicillin.

The researchers divided the patients into 4 groups according to age — 0-2 years, 3-6 years, 7-2 years, and 13-18 years. They further subdivided these groups according to the length of time between macrolide or penicillin exposure and hearing loss — 0-30 days, 31-90 days, 91-180 days, and 181-365 days.

After adjusting for all time frames from initiation of treatment to diagnosis of sensorineural hearing loss, pediatric patients treated with macrolides demonstrated a higher likelihood of developing sensorineural hearing loss compared with pediatric patients taking penicillin derivatives (adjusted odds ratio [aOR], 1.31; 95% CI, 1.05-1.64).

Sensorineural hearing loss diagnosed more than 180 days after macrolide exposure was significantly more likely than after penicillin exposure (aOR, 1.79; 95% CI, 1.23-2.60). Diagnosis of hearing loss during the 3 other shorter time periods did not significantly correlate with macrolide exposure, possibly reflecting delayed diagnosis due to a lack of recognition of milder symptoms of hearing loss.

“Macrolides are one of the most commonly used medications for children,” the researchers wrote. They added, “In an environment in which 56% of pediatric sensorineural hearing loss is idiopathic, the data from this study suggest that macrolides warrant further study as a potential risk factor…[and] may help direct parent counseling and the monitoring of exposed children, adolescents, and young adults.”

Study limitations included lack of ability to generate incidence data from case-control groups, lack of exclusion of patients with liver, kidney, or metabolic conditions which may affect the metabolism of macrolides and increase exposure risk, the possibility of coding errors and missing data, and the lack of information regarding weight-based dosage of prescriptions.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Dabekaussen KFAA, Andriotti T, Ye J, et al. Association of outpatient oral macrolide use with sensorineural hearing loss in children, adolescents, and young adultsJAMA Otolaryngol Head Neck Surg. Published online July 21, 2022. doi:10.1001/jamaoto.2022.1293

This article originally appeared on Neurology Advisor