Department of Respirology, St. Michael's Hospital and West Park Healthcare Centre, Rm 6-049, 30 Bond St, Toronto, ON, M5B 1W8, Canada.
Department of Surgery, University of Toronto, Toronto, Canada.
BMC Infect Dis. 2021 Mar 10;21(1):254. doi: 10.1186/s12879-021-05947-6.
The World Health Organization recommends intravenous amikacin for the treatment of MDR-TB at a dose of 15 mg/kg. However, higher doses are associated with significant toxicity.
Patients with MDR-TB treated at our institution receive amikacin at 8-10 mg/kg, with dose adjustment based on therapeutic drug monitoring. We conducted a retrospective cohort study of patients with MDR-TB who received amikacin between 2010 and 2016.
Forty-nine patients were included in the study. The median starting dose of amikacin was 8.9 mg/kg (IQR 8, 10), and target therapeutic drug levels were achieved at a median of 12 days (IQR 5, 26). The median duration of amikacin treatment was 7.2 months (IQR 5.7, 8), and median time to sputum culture conversion was 1 month (IQR 1,2). Six patients (12.2%) experienced hearing loss based on formal audiometry testing (95% CI 4.6-24.8%); 22.2% had subjective hearing loss (95% CI 11.2-37.1%) and 31.9% subjective tinnitus (95% CI 19.1-47.1%). Ten patients (23%) had a significant rise in serum creatinine (95% CI 11.8-38.6%), but only 5 patients had a GFR < 60 at treatment completion. 84% of patients had a successful treatment outcome (95% CI 84-99%).
Low dose amikacin is associated with relatively low rates of aminoglycoside-related adverse events. We hypothesize that low-dose amikacin can be used as a safe and effective treatment for MDR-TB in situations where an adequate regimen cannot be constructed with Group A and B drugs, and where careful monitoring for adverse events is feasible.
世界卫生组织推荐使用 15mg/kg 的静脉注射阿米卡星治疗耐多药结核病。然而，更高的剂量与显著的毒性相关。
我们机构治疗的耐多药结核病患者接受 8-10mg/kg 的阿米卡星治疗，并根据治疗药物监测进行剂量调整。我们对 2010 年至 2016 年期间接受阿米卡星治疗的耐多药结核病患者进行了回顾性队列研究。
本研究纳入了 49 名患者。阿米卡星的起始剂量中位数为 8.9mg/kg（IQR8,10），中位 12 天（IQR5,26）达到目标治疗药物浓度。阿米卡星治疗的中位持续时间为 7.2 个月（IQR5.7,8），中位痰培养转阴时间为 1 个月（IQR1,2）。根据正式的听力测试，有 6 名患者（12.2%）发生听力损失（95%CI4.6-24.8%）；22.2%的患者有主观听力损失（95%CI11.2-37.1%），31.9%的患者有主观耳鸣（95%CI19.1-47.1%）。10 名患者（23%）的血清肌酐显著升高（95%CI11.8-38.6%），但只有 5 名患者在治疗结束时的肾小球滤过率（GFR）<60。84%的患者有成功的治疗结果（95%CI84-99%）。
低剂量阿米卡星与氨基糖苷类药物相关不良事件的发生率相对较低。我们假设，在无法使用 A 组和 B 组药物构建适当方案的情况下，以及在能够进行不良事件的仔细监测的情况下，低剂量阿米卡星可用于耐多药结核病的安全有效治疗。
