在鸟分枝杆菌复杂肺部疾病中达到指南推荐的阿米卡星水平的挑战

IF 2 Q3 INFECTIOUS DISEASES

Journal of Clinical Tuberculosis and Other Mycobacterial Diseases Pub Date : 2025-01-31 DOI:10.1016/j.jctube.2025.100514

Takuya Akutsu , Kazuya Tone , Airi Hasegawa , Takaaki Kitayama , Shunsuke Inaki , Mina Gochi , Masamichi Takagi , Jun Araya

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引用次数: 0

摘要

背景：推荐在以大环内酯为基础的方案中添加氨基糖苷类药物治疗难治性鸟分枝杆菌复杂肺部疾病（MAC-PD）。对于静脉注射阿米卡星（AMK）， ATS/ERS/ESCMID/IDSA指南建议每周3次，峰值血清浓度为65-80µg/mL。然而，实现指南推荐的AMK浓度的可行性仍不清楚。方法从2018年到2022年，我们回顾性分析了每周3次AMK治疗≥3个月的难治性MAC-PD患者，并联合口服≥2种药物，包括大环内酯类药物。评价AMK的血药峰浓度及治疗效果。结果9例患者中位年龄70岁(范围：50 ~ 79岁；2男7女)。所有病例的病原菌均为鸟分枝杆菌。所有病例均表现出对AMK的敏感性，AMK的中位剂量为700 mg/天（15.8 mg/kg/天），中位持续时间为6个月。一名患者出现听力损失，导致AMK在4个月时停止使用。AMK峰浓度中位数为47.1 μg/mL，临床疗效组有高于无疗效组的趋势。除1例患者外，其余患者均未达到目标AMK峰浓度。结论在本初步研究中，大多数患者未达到指南推荐的MAC-PD AMK浓度。由于样本量小和回顾性设计，无法得出关于AMK浓度与临床结果之间关系的可靠结论。需要前瞻性随机对照试验来更好地确定AMK的疗效和安全性的最佳浓度。试验注册不适用。

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Challenges in achieving the guideline-recommended amikacin level for Mycobacterium avium complex pulmonary disease

Background

The addition of aminoglycosides to a macrolide-based regimen is recommended for refractory Mycobacterium avium complex pulmonary disease (MAC-PD). For intravenous amikacin (AMK) administration three times a week, the ATS/ERS/ESCMID/IDSA guidelines recommend targeting a peak serum concentration of 65–80 µg/mL. However, the feasibility of achieving the guideline-recommended AMK concentration remains unclear.

Methods

From 2018 to 2022, we retrospectively analyzed patients with refractory MAC-PD treated with AMK thrice weekly for ≥3 months combined with an oral regimen of ≥2 drugs, including macrolides. The peak serum concentration and therapeutic effects of AMK were evaluated.

Results

The median age of the 9 patients was 70 years (range: 50–79 years; 2 men and 7 women). The causative organism was M. avium in all cases. All cases demonstrated susceptibility to AMK, which was administered at a median dose of 700 mg/day (15.8 mg/kg/day) for a median duration of 6 months. One patient experienced hearing loss, which led to AMK discontinuation at 4 months. The median AMK peak concentration was 47.1 μg/mL, with a tendency to be higher in the clinical efficacy group compared to the nonefficacy group. None of patient, except one, achieved the target AMK peak concentration.

Conclusions

In this preliminary study, the guideline-recommended AMK concentration for MAC-PD was not achieved in the majority of patients. Due to the small sample size and retrospective design, robust conclusions regarding the association between AMK concentrations and clinical outcomes could not be drawn. Prospective randomized controlled trials are required to better define the optimal AMK concentration for efficacy and safety.

Trial registration

Not applicable.

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来源期刊

Journal of Clinical Tuberculosis and Other Mycobacterial Diseases Medicine-Pulmonary and Respiratory Medicine

CiteScore

4.00

自引率

5.00%

发文量

审稿时长

30 weeks

期刊介绍： Journal of Clinical Tuberculosis and Mycobacterial Diseases aims to provide a forum for clinically relevant articles on all aspects of tuberculosis and other mycobacterial infections, including (but not limited to) epidemiology, clinical investigation, transmission, diagnosis, treatment, drug-resistance and public policy, and encourages the submission of clinical studies, thematic reviews and case reports. Journal of Clinical Tuberculosis and Mycobacterial Diseases is an Open Access publication.