Background Macrolides are widely prescribed antibiotics for many different indications. However, there are concerns about adverse effects such as ototoxicity. Objectives To investigate whether macrolide use is associated with tinnitus and hearing loss in the general population. Methods Cross-sectional (n = 4286) and longitudinal (n = 636) analyses were performed within the population-based Rotterdam Study. We investigated with multivariable logistic regression models the association between macrolides and tinnitus, and with multivariable linear regression models the association between macrolides and two different hearing thresholds (both ears, averaged over 0.25, 0.5, 1, 2, 4 and 8 kHz and 2, 4 and 8 kHz). Both regression models were adjusted for age, sex, systolic blood pressure, alcohol, smoking, BMI, diabetes, education level, estimated glomerular filtration rate and other ototoxic or tinnitus-generating drugs. Cumulative exposure to macrolides was categorized according to the number of dispensed DDDs and duration of action. Results In the fully adjusted model, ever use of macrolides was associated with a 25% higher likelihood of prevalent tinnitus (OR = 1.25; 95% CI 1.07–1.46). This association was more prominent in participants with a cumulative dose of more than 14 DDDs and among users of intermediate- or long-acting macrolides. Macrolide use in between both assessments was associated with more than a 2-fold increased risk on incident tinnitus. No general association between macrolides and hearing loss was observed. A borderline significant higher hearing threshold in very recent users (≤3 weeks) was found. Conclusions Macrolide use was significantly associated with both prevalent and incident tinnitus. Macrolide-associated tinnitus was likely cumulative dose-dependent.

中文翻译：

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大环内酯类耳毒性：一项横断面和纵向研究评估大环内酯类使用与耳鸣和听力损失的关系

背景 大环内酯类是广泛用于许多不同适应症的抗生素。然而，人们担心耳毒性等副作用。目的 调查大环内酯类药物的使用是否与普通人群的耳鸣和听力损失有关。方法 在基于人群的鹿特丹研究中进行横断面 (n = 4286) 和纵向 (n = 636) 分析。我们使用多变量逻辑回归模型研究了大环内酯类药物与耳鸣之间的关联，并使用多变量线性回归模型研究了大环内酯类药物与两种不同听力阈值（双耳，平均超过 0.25、0.5、1、2、4 和 8 kHz 以及 2、 4 和 8 kHz）。两个回归模型都针对年龄、性别、收缩压、酒精、吸烟、BMI、糖尿病、教育水平、估计肾小球滤过率和其他产生耳毒性或耳鸣的药物。大环内酯类的累积暴露量根据分配的 DDD 数量和作用持续时间进行分类。结果 在完全调整的模型中，曾经使用过大环内酯类药物与流行耳鸣的可能性增加 25% 相关（OR = 1.25；95% CI 1.07–1.46）。这种关联在累积剂量超过 14 种 DDD 的参与者以及中效或长效大环内酯类药物的使用者中更为突出。在两次评估之间使用大环内酯与耳鸣事件风险增加 2 倍以上有关。未观察到大环内酯类与听力损失之间的一般关联。在最近的用户（≤3 周）中发现了临界显着更高的听力阈值。结论 大环内酯类药物的使用与耳鸣的流行和耳鸣事件显着相关。大环内酯相关的耳鸣可能是累积剂量依赖性的。