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台湾肺部感染分离出的复杂物种之间的异质性。

Heterogeneity among complex species isolated from pulmonary infection in Taiwan.

作者信息

Lin Hsiu-Mei, Shu Chin-Chung, Chen Chun-Hao, Chen Nan-Yu, Yang Jeng-How, Chen Chih-Hung, Li Shih-Hong, Wang Chih-Liang, Yu Chih-Teng, Lin Shu-Min, Kao Kuo-Chin, Huang Chung-Chi, Yang Cheng-Ta, Lu Jang-Jih, Chiu Cheng-Hsun, Lai Hsin-Chih, Wu Ting-Shu

机构信息

Department of Family Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University School of Medicine, , Taipei, Taiwan.

出版信息

Microbiol Spectr. 2025 Jul 7:e0030925. doi: 10.1128/spectrum.00309-25.

DOI:10.1128/spectrum.00309-25
PMID:40621928
Abstract

complex (MAC) is an emerging pathogen causing nontuberculous pulmonary infections globally. However, clinical treatment guidelines regard MAC as a single entity, recommending a universal anti-mycobacterial combination therapy. Our study aimed to distinguish species among MAC and investigate the antimicrobial susceptibility for the selection of optimal antimicrobial agents in Taiwan. Two hundred ninety-four consecutive sputum samples confirmed as MAC by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were collected from 1 November 2015 to 31 August 2020 at Linkou Chang Gung Memorial Hospital in Taiwan. These isolates were identified through 16S rRNA gene, 23S rRNA gene, heat-shock protein 65 gene (), internal transcribed spacer, and beta subunit of RNA polymerase () gene sequencing and phylogenetic analyses. Antimicrobial susceptibility testing (AST) was performed with 13 antimicrobial agents. The predominant pathogen identified was clade A (122/294, 41.5%), followed by subsp. (87/294, 29.6%), subsp. (39/294, 13.3%), (35/294, 11.9%), and four other species (11/294, 3.7%). AST showed that clarithromycin and amikacin had high susceptibility rates against clade A, subsp. , subsp. and , while linezolid and moxifloxacin exhibited higher resistance. The comparison of minimum inhibitory concentrations among species within the same antimicrobial agent showed variability in susceptibility. A diverse clonality of might exist in MAC pulmonary infections in Taiwan. Among MAC species, exhibited multidrug resistance. Although international guidelines recommend macrolide, ethambutol, and rifampin for treating MAC pulmonary disease, our study highlights the importance of considering species identification and regional AST results when selecting anti-mycobacterial agents.IMPORTANCEThere are more than 10 (sub)species within the complex. According to modern biotechnology, such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, it is still difficult to differentiate the complex into specific species precisely. We utilize concatenated multi-gene sequencing to classify this complex at the (sub)species level. Indeed, we encountered poorer treatment outcomes when facing pulmonary infections compared to other species causing pulmonary infections. Individualized anti-mycobacterial therapy should focus on each species responsible for pulmonary disease.

摘要

鸟分枝杆菌复合体(MAC)是一种新出现的病原体,在全球范围内引起非结核性肺部感染。然而,临床治疗指南将MAC视为一个单一实体,推荐通用的抗分枝杆菌联合疗法。我们的研究旨在区分MAC中的菌种,并调查台湾地区的抗菌药敏情况,以选择最佳抗菌药物。2015年11月1日至2020年8月31日期间,在台湾林口长庚纪念医院收集了294份经基质辅助激光解吸/电离飞行时间质谱确认为MAC的连续痰液样本。通过16S rRNA基因、23S rRNA基因、热休克蛋白65基因()、内部转录间隔区和RNA聚合酶β亚基()基因测序及系统发育分析对这些分离株进行鉴定。使用13种抗菌药物进行抗菌药敏试验(AST)。鉴定出的主要病原体是A群(122/294,41.5%),其次是亚种(87/294,29.6%)、亚种(39/294,13.3%)、(35/294,11.9%)和其他4个菌种(11/294,3.7%)。AST显示,克拉霉素和阿米卡星对A群、亚种、亚种和的药敏率较高,而利奈唑胺和莫西沙星耐药性较高。同一抗菌药物内不同菌种的最低抑菌浓度比较显示药敏存在差异。台湾地区MAC肺部感染中可能存在多种不同的克隆型。在MAC菌种中,表现出多重耐药性。尽管国际指南推荐大环内酯类、乙胺丁醇和利福平用于治疗MAC肺部疾病,但我们的研究强调了在选择抗分枝杆菌药物时考虑菌种鉴定和地区AST结果的重要性。重要性鸟分枝杆菌复合体中有10多个(亚)种。根据现代生物技术,如基质辅助激光解吸/电离飞行时间质谱,仍难以精确区分该复合体中的具体菌种。我们利用多基因串联测序在(亚)种水平对该复合体进行分类。事实上,与其他引起肺部感染的菌种相比,我们在面对肺部感染时遇到了较差治疗效果。个体化抗分枝杆菌治疗应针对引起肺部疾病的每个菌种。

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Accurate subspecies-level identification of clinically significant Mycobacterium avium and Mycobacterium intracellulare by whole-genome sequencing.通过全基因组测序对临床重要的鸟分枝杆菌和胞内分枝杆菌进行准确的亚种水平鉴定。
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非结核分枝杆菌肺病由复杂疾病负担、未满足的需求以及治疗进展引起。
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