Department of Health & Rehabilitation Sciences, University of Cape Town, Cape Town, South Africa.
Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa.
Int J Audiol. 2020 Mar;59(3):219-223. doi: 10.1080/14992027.2019.1690170. Epub 2019 Nov 18.
The toxicity associated with the use of kanamycin includes irreversible hearing loss. There are limited data describing the relationship between hearing loss and kanamycin pharmacokinetics (PK). We explored the association of kanamycin PK with hearing loss in patients on MDR-TB treatment. We prospectively recruited patients on kanamycin-based MDR-TB treatment in Cape Town. Hearing thresholds from 0.25 to 16 kHz were tested at baseline and at 4, 8 and 12 weeks. We determined kanamycin concentrations at steady-state in serial plasma samples over 10 h, and explored factors associated with hearing loss. One hundred and two participants including 58 (56.9%) men had analysable audiometric data; median age was 34.9 years, 65 (63.7%) were HIV-positive, and 24 (23.5%) had been treated for MDR-TB previously. Eighty-four participants (82.4%) developed hearing loss. We found a 3% (95% CI: 1-6%, = 0.028) increased risk of cochleotoxicity for each 10 µg h/L increase in 0-10 h AUC. We describe a high incidence of hearing loss in MDR-TB patients treated with kanamycin, with higher AUC significantly associated with hearing loss.
使用卡那霉素相关的毒性包括不可逆转的听力损失。描述听力损失与卡那霉素药代动力学（PK）之间关系的数据有限。我们探讨了卡那霉素 PK 与耐多药结核病（MDR-TB）治疗患者听力损失的关系。我们前瞻性地招募了开普敦基于卡那霉素的 MDR-TB 治疗患者。在基线和 4、8 和 12 周时测试了 0.25 至 16 kHz 的听力阈值。我们在 10 小时的时间内连续测定了稳态时的卡那霉素浓度，并探讨了与听力损失相关的因素。102 名参与者包括 58 名（56.9%）男性有可分析的听力数据；中位年龄为 34.9 岁，65 名（63.7%）HIV 阳性，24 名（23.5%）以前接受过 MDR-TB 治疗。84 名参与者（82.4%）出现听力损失。我们发现，0-10 小时 AUC 每增加 10µg h/L，耳蜗毒性的风险增加 3%（95%CI：1-6%， = 0.028）。我们描述了耐多药结核病患者使用卡那霉素治疗时听力损失的发生率很高，AUC 较高与听力损失显著相关。
