The Association between Aminoglycoside Exposure and Ototoxicity in Children with Cystic Fibrosis

Pulmonary exacerbations increase the requirement of aminoglycoside (AG) antibiotics in people with cystic fibrosis (pwCF). Several studies have shown that AGs have a cumulative effect on ototoxicity. We aimed to investigate the relationship between AG exposure and ototoxicity by using 3 different methods in patients with CF.

The multicenter study included 121 pwCF aged between 5 and 18 years with a history of parenteral AG exposure. Standard pure-tone audiometry, extended high-frequency pure-tone audiometry (EHF-PTA), and distortion-product otoacoustic emissions (DPOAE) tests were performed. Mitochondrial mutation analysis for m1555G>A was performed in 61 patients.

Median age was 12.85 years and 52.1% (n = 63) were male. 18.2% (n = 22) of the patients had received parenteral AGs more than 5 courses/lifetime. Ototoxicity was detected in at least one of the tests in 56.2% (n = 68) of the patients. Only 10.7% (n = 13) of the patients had reported a symptom indicating ototoxicity. 30.3% (n = 30) of the patients had ototoxicity in the low exposure group, while it was 45.5% (n = 10) in the high exposure group according to EHF-PTA (p > 0.05). Median number of parenteral amikacin courses was significantly higher in the ototoxic group (2 [1.25-5.75] vs. 2 [1-3]; p = 0.045). No m1555A>G mutation was detected in 61 patients who screened for mitochondrial mutation analysis.

As AG ototoxicity occurs primarily at high frequencies, EHF-PTA is important in early detecting ototoxicity. EHF-PTA and DPOAE detected ototoxicity in some patients with normal PTA results. All pwCF with a history of AG exposure should be evaluated for hearing loss since symptoms may only be noticed in the late period.