The prolonged use of injectable agents in a regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) is recommended by the World Health Organization, despite its association with ototoxicity and nephrotoxicity. We undertook this study to look at the relative adverse effects of capreomycin and amikacin. We reviewed the case notes of 100 consecutive patients treated at four MDR-TB treatment centers in the United Kingdom. The median total duration of treatment with an injectable agent was 178 days (interquartile range [IQR], 109 to 192 days; n = 73) for those with MDR-TB, 179 days (IQR, 104 to 192 days; n = 12) for those with MDR-TB plus fluoroquinolone resistance, and 558 days (IQR, 324 to 735 days; n = 8) for those with extensively drug-resistant tuberculosis (XDR-TB). Injectable use was longer for those started with capreomycin (183 days; IQR, 123 to 197 days) than those started with amikacin (119 days; IQR, 83 to 177 days) (P = 0.002). Excluding patients with XDR-TB, 51 of 85 (60%) patients were treated with an injectable for over 6 months and 12 of 85 (14%) were treated with an injectable for over 8 months. Forty percent of all patients discontinued the injectable due to hearing loss. Fifty-five percent of patients experienced ototoxicity, which was 5 times (hazard ratio [HR], 5.2; 95% confidence interval [CI], 1.2 to 22.6; P = 0.03) more likely to occur in those started on amikacin than in those treated with capreomycin only. Amikacin was associated with less hypokalemia than capreomycin (odds ratio, 0.28; 95% CI, 0.11 to 0.72), with 5 of 37 (14%) patients stopping capreomycin due to recurrent electrolyte loss. There was no difference in the number of patients experiencing a rise in the creatinine level of >1.5 times the baseline level. Hearing loss is frequent in this cohort, though its incidence is significantly lower in those starting capreomycin, which should be given greater consideration as a first-line agent.
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机译：尽管有耳毒性和肾毒性，世界卫生组织还是建议在治疗耐多药结核病（MDR-TB）的方案中长期使用注射剂。我们进行了这项研究，以观察红霉素和丁胺卡那霉素的相对不良反应。我们回顾了英国四个耐多药结核病治疗中心连续治疗的100名患者的病例记录。耐多药结核病患者的平均总持续时间为178天（四分位间距[IQR]，109至192天； n = 73），耐多药结核病患者的平均中位时间为179天（IQR，104至192天； n = 12）那些对耐多药结核病加氟喹诺酮类药物具有耐药性，对于那些广泛耐药结核病（XDR-TB）则为558天（IQR，324至735天； n = 8）。以开普霉素开始的患者（183天； IQR，123至197天）的注射使用时间比以阿米卡星开始的患者（119天； IQR，83至177天）的注射使用时间更长（P = 0.002）。除XDR-TB患者外，在85名患者中有51名（60％）接受了6个月以上的注射治疗，在85名患者中有12名（14％）接受了8个月以上的注射治疗。由于听力损失，所有患者中有40％停止注射。 55％的患者发生耳毒性，比起丁胺卡那霉素的患者发生耳毒性的可能性高5倍（危险比[HR]，5.2； 95％置信区间[CI]，1.2至22.6； P = 0.03）仅用红霉素治疗。阿米卡星与低钾血症的发生率比红霉素低（比值比为0.28； 95％CI为0.11至0.72），其中37例患者中有5例（14％）由于反复流失电解质而停止使用红霉素。肌酐水平升高>基线水平的1.5倍的患者数量没有差异。尽管该人群在开始使用卡普霉素的人群中其发生率明显较低，但听力损失在该人群中还是很常见的，因此应作为一线药物给予更多考虑。
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