Yilmaz Yegit Cansu, Ergenekon Pinar, Yanaz Mürüvvet, Ozturk Akar Nezafet, Toktas Yavuz Fatma, Molla Kafi Hale, Çollak Abdülhamit, Bal Nilüfer, Gedik Toker Özge, Meral Özge, Ataş Ahmet, Çetin Kara Halide, Ayhan Yetkin, Guliyeva Aynur, Yuksel Kalyoncu Mine, Selçuk Balcı Merve, Karabulut Şeyda, Taştan Gamze, Uzunoglu Burcu, Karasu Nesibe, Oruc Yesim, Acar Melda, Yumuşakhuylu Ali Cemal, Dogan Remzi, Gozen Tan Emine Deniz, Ata Pinar, Kılınç Sakallı Ayşe Ayzıt, Girit Saniye, Cakir Erkan, Gokdemir Yasemin, Erdem Eralp Ela, Ciprut Ayca, Karakoc Fazilet, Karadag Bulent
Division of Pediatric Pulmonology, Marmara University, School of Medicine, Istanbul, Turkey.
Health Science Institute, Marmara University, Istanbul, Turkey.
Respiration. 2025;104(1):48-57. doi: 10.1159/000541447. Epub 2024 Sep 19.
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.
MATERIALS/METHODS: 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.
肺部加重会增加囊性纤维化患者(pwCF)对氨基糖苷类(AG)抗生素的需求。多项研究表明,AGs对耳毒性有累积作用。我们旨在通过三种不同方法研究CF患者中AG暴露与耳毒性之间的关系。
材料/方法:这项多中心研究纳入了121名年龄在5至18岁之间有肠外AG暴露史的pwCF患者。进行了标准纯音听力测定、扩展高频纯音听力测定(EHF-PTA)和畸变产物耳声发射(DPOAE)测试。对61名患者进行了m1555G>A线粒体突变分析。
中位年龄为12.85岁,52.1%(n = 63)为男性。18.2%(n = 22)的患者接受肠外AGs超过5个疗程/一生。56.2%(n = 68)的患者在至少一项测试中检测到耳毒性。只有10.7%(n = 13)的患者报告有表明耳毒性的症状。根据EHF-PTA,低暴露组30.3%(n = 30)的患者有耳毒性,而高暴露组为45.5%(n = 10)(p>0.05)。耳毒性组肠外阿米卡星疗程的中位数显著更高(2 [1.25 - 5.75] 对 2 [1 - 3];p = 0.045)。在61名接受线粒体突变分析筛查的患者中未检测到m1555A>G突变。
由于AG耳毒性主要发生在高频,EHF-PTA对早期检测耳毒性很重要。EHF-PTA和DPOAE在一些纯音听力测定(PTA)结果正常的患者中检测到了耳毒性。所有有AG暴露史的pwCF患者都应进行听力损失评估,因为症状可能仅在晚期才被注意到。