Sound Pharmaceuticals, Inc., 4010 Stone Way N, Ste 120, Seattle, WA, 98103, United States.
Sound Pharmaceuticals, Inc., 4010 Stone Way N, Ste 120, Seattle, WA, 98103, United States.
J Cyst Fibros. 2021 Mar;20(2):288-294. doi: 10.1016/j.jcf.2020.11.020. Epub 2020 Dec 16.
Aminoglycosides are commonly used to treat infections in CF patients and are highly ototoxic. The incidence of tobramycin-induced hearing loss, tinnitus, vertigo or dizziness (ototoxicity) varies widely from 0 to 56% secondary to variation in patient enrollment, dosing, audiometry, and ototoxic criteria. The aim of this study is to determine the incidence of ototoxicity after one course of once-daily IV tobramycin in CF patients. Adult CF patients with acute pulmonary exacerbations were enrolled on IV tobramycin (10 mg/kg/d, ≥10 days). Pure-tone audiometry was performed for standard and extended high frequencies in the sensitive range for ototoxicity (SRO). American-Speech-Language-Hearing-Association cochleotoxicity criteria were applied. Distortion product otoacoustic emissions (DPOAE) and the words-in-noise-test (WINT) were assessed. Tinnitus Functional Index (TFI) and Vertigo Symptoms Scale (VSS) were used. Eighteen CF patients, mean age 31.1 (18-59), were enrolled. The incidence of cochleotoxic change from baseline at 2 and 4 weeks post-treatment was 89% and 93%. For DPOAE, a measure of outer hair-cell function, the incidence of ≥5 dB decrease was 82% and 80%. For WINT, a measure of word recognition, the incidence of ≥10% decrease was 17% and 40%. For TFI, the incidence of ≥10pt increase was 12% and 8%, and for VSS, the incidence of ≥6pt increase was 0% and 8%. One course of IV tobramycin was sufficient to cause hearing loss and other ototoxic symptoms four weeks after treatment ended. Audiometric measures were more sensitive to ototoxic change than TFI & VSS. Age and duration of tobramycin treatment were not obvious factors for predicting ototoxicity.
氨基糖苷类药物通常用于治疗 CF 患者的感染,具有高度耳毒性。妥布霉素引起的听力损失、耳鸣、眩晕或头晕(耳毒性)的发生率因患者入组、剂量、听力测试和耳毒性标准的不同而有很大差异,范围为 0 至 56%。本研究旨在确定 CF 患者接受一次每日一次静脉注射妥布霉素治疗后耳毒性的发生率。患有急性肺部恶化的成年 CF 患者被纳入 IV 妥布霉素(10mg/kg/d,≥10 天)治疗。在敏感范围(SRO)内进行标准和扩展高频纯音听力测试。采用美国言语-语言-听力协会的耳蜗毒性标准。评估畸变产物耳声发射(DPOAE)和噪声中言语测试(WINT)。使用耳鸣功能指数(TFI)和眩晕症状量表(VSS)。18 名 CF 患者,平均年龄 31.1(18-59)岁,入组。治疗后 2 周和 4 周时从基线开始的耳蜗毒性变化发生率分别为 89%和 93%。对于 DPOAE,一种外毛细胞功能的测量方法,≥5dB 下降的发生率为 82%和 80%。对于 WINT,一种言语识别的测量方法,≥10%下降的发生率为 17%和 40%。对于 TFI,≥10 分增加的发生率为 12%和 8%,对于 VSS,≥6 分增加的发生率为 0%和 8%。一个疗程的 IV 妥布霉素足以在治疗结束后四周引起听力损失和其他耳毒性症状。听力测量比 TFI 和 VSS 更能敏感地反映耳毒性变化。年龄和妥布霉素治疗时间不是预测耳毒性的明显因素。