Kodama Tatsuya, Aono Akio, Fujiwara Keiji, Furuuchi Koji, Ito Masashi, Kamada Keisuke, Watanabe Fumiya, Chikamatsu Kinuyo, Igarashi Yuriko, Murase Yoshiro, Ogata Hideo, Shiraishi Yuji, Yoshiyama Takashi, Ohta Ken, Mitarai Satoshi, Morimoto Kozo
Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan.
Department of Basic Mycobacteriology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
ERJ Open Res. 2025 Aug 11;11(4). doi: 10.1183/23120541.01084-2024. eCollection 2025 Jul.
Although the incidence of amikacin (AMK)-resistant complex (MAC) pulmonary disease (PD) is suspected to have increased, limited data are available on AMK-resistant MAC-PD. This study evaluated the risk factors associated with AMK resistance, the molecular characteristics of the AMK-resistant isolates, and treatment outcomes of patients with AMK-resistant MAC-PD.
This retrospective case-control study included 73 patients with severe and refractory MAC-PD who had a history of aminoglycoside drug use. Patients with initial and repeat AMK minimum inhibitory concentration (MIC) ≥64 μg·mL were classified as AMK-resistant. To clarify the clinical outcomes and prognosis, an observational study was conducted. 21 patients with AMK resistance (AMK-resistant) and 52 controls (AMK-susceptible) were analysed.
In all cases of AMK resistance where previous isolates were available, the AMK MICs were elevated compared to the levels prior to aminoglycoside administration. In the multivariate analysis of risk factors, clarithromycin resistance (OR 6.31, 95% CI 1.68-23.7) and >12 months of total duration of aminoglycoside use (OR 4.69, 95% CI 1.09-20.2) were identified as independent risk factors for AMK resistance. 12 (57%) out of 21 AMK-resistant isolates were found to have mutations in the region. There was a significant difference between the AMK-resistant and AMK-susceptible groups in terms of worsening outcomes, including the introduction of home oxygen therapy (38% 12%; p=0.01) and 3-year mortality (33% 10%; p=0.02).
Better management strategies for patients with severe and refractory MAC-PD are crucial. This includes placing a strong emphasis on preventing AMK resistance.
尽管怀疑耐阿米卡星（AMK）的非结核分枝杆菌复合群（MAC）肺病（PD）的发病率有所增加，但关于耐AMK的MAC-PD的数据有限。本研究评估了与AMK耐药相关的危险因素、耐AMK分离株的分子特征以及耐AMK的MAC-PD患者的治疗结果。
这项回顾性病例对照研究纳入了73例有氨基糖苷类药物使用史的重度难治性MAC-PD患者。初始和重复AMK最低抑菌浓度（MIC）≥64μg·mL的患者被分类为耐AMK。为了阐明临床结果和预后，进行了一项观察性研究。分析了21例耐AMK患者（耐AMK组）和52例对照患者（AMK敏感组）。
在所有有既往分离株的耐AMK病例中，与氨基糖苷类药物给药前相比，AMK的MIC升高。在危险因素的多变量分析中，克拉霉素耐药（比值比6.31，95%置信区间1.68 - 23.7）和氨基糖苷类药物总使用时长>12个月（比值比4.69，95%置信区间1.09 - 20.2）被确定为AMK耐药的独立危险因素。21株耐AMK分离株中有12株（57%）在该区域发现有突变。耐AMK组和AMK敏感组在病情恶化结果方面存在显著差异，包括开始家庭氧疗（38%对12%；p = 0.01）和3年死亡率（33%对10%；p = 0.02）。
对于重度难治性MAC-PD患者，更好的管理策略至关重要。这包括高度重视预防AMK耐药。
