Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas; Children's Medical Center, University of Texas Southwestern Medical Center, Dallas, Texas.
Pediatr Blood Cancer. 2013 Nov;60(11):1772-7. doi: 10.1002/pbc.24631. Epub 2013 Jun 20.
Children undergoing cancer therapy often receive aminoglycosides to treat febrile neutropenia or gram-negative infections. The magnitude of the risk of developing aminoglycoside-induced ototoxicity and the dose threshold at which that risk significantly increases are unknown.
Eligible cancer patients received the aminoglycoside amikacin at Children's Medical Center between 2004 and 2007. They were aged 3-8 years; were without prior hearing loss; had no platinum-based chemotherapy, cranial radiation, nor bone marrow transplant; and received no loop diuretics within 6 weeks of testing. Consenting patients underwent complete hearing and vestibular testing.
We tested 23 patients who had significant amikacin exposure. Three (13%) had abnormal hearing tests, and four (17%) had subclinical vestibular dysfunction; none had both. Of those with hearing loss, two were known to have developed hearing loss after aminoglycoside exposure, but the third had moderate to severe high-frequency sensorineural hearing loss bilaterally that had been undiagnosed. We observed clear dose-dependent ototoxicity; of the eight patients who received amikacin for a cumulative total of more than 50 days, five (68%) developed toxicity. Similarly, of the seven who received a cumulative total of more than 1,200 mg/kg, five developed toxicity.
These data highlight the risks of prolonged aminoglycoside administration and warrant further validation in a larger group of patients. Patients to be treated with prolonged aminoglycoside therapy may benefit from prospective hearing screening.
接受癌症治疗的儿童常接受氨基糖苷类药物来治疗发热性中性粒细胞减少症或革兰氏阴性感染。氨基糖苷类药物引起耳毒性的风险程度以及风险显著增加的剂量阈值尚不清楚。
2004 年至 2007 年间，符合条件的癌症患儿在儿童医疗中心接受氨基糖苷类药物阿米卡星治疗。患儿年龄在 3-8 岁之间；无听力损失史；未接受过含铂化疗、颅放疗或骨髓移植；且在检测前 6 周内未使用过噻嗪类利尿剂。同意的患儿接受了全面的听力和前庭测试。
我们测试了 23 名有显著阿米卡星暴露的患者。3 名（13%）听力测试异常，4 名（17%）有亚临床前庭功能障碍；均无两者兼具者。在有听力损失的患者中，2 名已知在氨基糖苷类药物暴露后发生了听力损失，但第 3 名双侧出现了中度至重度高频感音神经性听力损失，此前并未被诊断出来。我们观察到明显的剂量依赖性耳毒性；在接受累计超过 50 天阿米卡星治疗的 8 名患者中，有 5 名（68%）发生了毒性。同样，在接受累计超过 1200mg/kg 的 7 名患者中，有 5 名发生了毒性。
这些数据突出了长期氨基糖苷类药物给药的风险，需要在更大的患者群体中进一步验证。需要长期氨基糖苷类药物治疗的患者可能受益于前瞻性听力筛查。
