Jiang Meiyan, Taghizadeh Farshid, Steyger Peter S
Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR, United States.
National Center for Rehabilitative Auditory Research, VA Portland Health Care System, Portland, OR, United States.
Front Cell Neurosci. 2017 Nov 21;11:362. doi: 10.3389/fncel.2017.00362. eCollection 2017.
Aminoglycoside antibiotics remain widely used for urgent clinical treatment of life-threatening infections, despite the well-recognized risk of permanent hearing loss, i.e., cochleotoxicity. Recent studies show that aminoglycoside-induced cochleotoxicity is exacerbated by bacteriogenic-induced inflammation. This implies that those with severe bacterial infections (that induce systemic inflammation), and are treated with bactericidal aminoglycosides are at greater risk of drug-induced hearing loss than previously recognized. Incorporating this novel comorbid factor into cochleotoxicity risk prediction models will better predict which individuals are more predisposed to drug-induced hearing loss. Here, we review the cellular and/or signaling mechanisms by which host-mediated inflammatory responses to infection could enhance the trafficking of systemically administered aminoglycosides into the cochlea to enhance the degree of cochleotoxicity over that in healthy preclinical models. Once verified, these mechanisms will be potential targets for novel pharmacotherapeutics that reduce the risk of drug-induced hearing loss (and acute kidney damage) without compromising the life-saving bactericidal efficacy of aminoglycosides.
氨基糖苷类抗生素尽管存在公认的永久性听力丧失风险，即耳蜗毒性，但仍广泛用于危及生命感染的紧急临床治疗。最近的研究表明，细菌感染引起的炎症会加剧氨基糖苷类药物诱发的耳蜗毒性。这意味着，那些患有严重细菌感染（诱发全身炎症）并接受杀菌性氨基糖苷类药物治疗的人，发生药物性听力损失的风险比之前认为的更高。将这一新的合并症因素纳入耳蜗毒性风险预测模型，将能更好地预测哪些个体更容易发生药物性听力损失。在此，我们综述宿主介导的感染炎症反应增强全身给药的氨基糖苷类药物向耳蜗转运从而提高耳蜗毒性程度（相较于健康临床前模型）的细胞和/或信号传导机制。一旦得到验证，这些机制将成为新型药物治疗的潜在靶点，可降低药物性听力损失（以及急性肾损伤）风险，同时不影响氨基糖苷类药物挽救生命的杀菌效力。
