Gentamicin (brand names Garamycin, Cidomycin, and Septopal) is an aminoglycoside antibiotic that is used to treat sepsis. Gentamicin is administered by injection to treat serious infections caused by gram-negative bacteria (for example, , species, , species, and species). Additionally, gentamicin is used as an adjuvant treatment for infections caused by gram-positive bacteria (such as species) (1). Gentamicin may also be used topically to treat ophthalmic and dermatological infections. In most individuals, prolonged exposure to high gentamicin levels will cause ototoxicity (damage to the inner ear). However, among individuals who have specific variants in the mitochondrial gene , a single dose of gentamicin can result in hearing loss (cochleotoxicity). This toxicity occurs in genetically susceptible individuals, despite serum drug concentrations within the normal therapeutic range (2). This hearing loss can be triggered not only by gentamicin, but by other aminoglycoside antibiotics and is referred to as aminoglycoside-induced hearing loss (AIHL). Substantial literature has reported that a high proportion of individuals with the m.1555A>G variant (NC_012920.1:m.1555A>G) develop hearing loss after receiving aminoglycoside therapy. The onset of hearing loss among these individuals varies, but once it occurs, it is usually moderate to profound, bilateral, and irreversible (3). Additional genotypes associated with increased risk of AIHL include m.1095T>C and m.1494C>T (4). The FDA-approved drug label for gentamicin does not include a statement regarding (5); however, the Clinical Pharmacogenetics Implementation Consortium (CPIC) has published guidelines for administration of aminoglycosides, including gentamicin, with respect to variants in the gene (4). These guidelines (Table 1) recommend avoiding the use of aminoglycoside antibiotics, such as gentamicin unless there are no satisfactory alternatives, by individuals who have a genotype that puts them at high risk for AIHL. The CPIC guideline further advises that individuals with normal-risk alleles or uncertain-risk alleles at the locus should all use aminoglycosides at standard doses for the shortest feasible course, with regular evaluation for hearing loss. This extends the 2014 American College of Medical Genetics and Genomics guideline with the following recommendation: “Single-gene testing may be warranted in cases in which the medical or family history, or presentation of the hearing loss, suggests a specific etiology. For example, testing for mitochondrial DNA variants associated with aminoglycoside ototoxicity may be considered for individuals with a history of use of aminoglycoside antibiotics” (6, 7).
庆大霉素（商品名：加新霉素、西多霉素和塞普托）是一种氨基糖苷类抗生素，用于治疗败血症。庆大霉素通过注射给药，用于治疗由革兰氏阴性菌引起的严重感染（例如， 菌属、 菌属、 菌属和 菌属）。此外，庆大霉素还用作革兰氏阳性菌（如 菌属）引起的感染的辅助治疗药物(1)。庆大霉素也可局部用于治疗眼科和皮肤感染。在大多数个体中，长时间暴露于高浓度庆大霉素会导致耳毒性（内耳损伤）。然而，在线粒体基因 有特定变异的个体中，单剂量庆大霉素就可导致听力丧失（耳蜗毒性）。尽管血清药物浓度在正常治疗范围内，但这种毒性仍会在基因易感性个体中发生(2)。这种听力丧失不仅可由庆大霉素引发，也可由其他氨基糖苷类抗生素引发，被称为氨基糖苷类抗生素所致听力丧失（AIHL）。大量文献报道，携带m.1555A>G变异（NC_012920.1:m.1555A>G）的个体在接受氨基糖苷类治疗后有很大比例会出现听力丧失。这些个体听力丧失的发病情况各不相同，但一旦发生，通常为中度至重度、双侧且不可逆(3)。与AIHL风险增加相关的其他 基因型包括m.1095T>C和m.1494C>T(4)。美国食品药品监督管理局（FDA）批准的庆大霉素药品标签未包含有关 的声明(5)；然而，临床药物基因组学实施联盟（CPIC）已发布关于氨基糖苷类药物（包括庆大霉素）给药的指南，涉及 基因变异(4)。这些指南（表1）建议，对于有 基因型且处于AIHL高风险的个体，除非没有令人满意的替代药物，否则应避免使用氨基糖苷类抗生素，如庆大霉素。CPIC指南进一步建议，在 位点具有正常风险等位基因或不确定风险等位基因的个体均应以标准剂量使用氨基糖苷类药物，并尽可能缩短疗程，同时定期评估听力丧失情况。这扩展了2014年美国医学遗传学与基因组学学会的指南，其建议如下：“在医学史或家族史或听力丧失表现提示特定病因的情况下，可能需要进行单基因检测。例如，对于有氨基糖苷类抗生素使用史的个体，可考虑检测与氨基糖苷类耳毒性相关的线粒体DNA变异”(6, 7)。
