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中国北京临床复杂样本中已知耐药基因对表型耐药的预测能力有限。

Limited predictive power of known resistance genes for phenotypic drug resistance in clinical complex from Beijing in China.

作者信息

Hou Yue, Pi Rui, Jia Junnan, Wu Zhaojun, Huo Fengmin, Zhou Yu, Jiang Hui, Takiff Howard E, Zhu Chendi, Wang Wei, Li Weimin

机构信息

Beijing Chest Hospital, Capital Medical University, Beijing, China.

Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.

出版信息

Antimicrob Agents Chemother. 2025 Jul 2;69(7):e0184724. doi: 10.1128/aac.01847-24. Epub 2025 May 27.

Abstract

complex (MABC) is an emerging pathogen with intrinsic multidrug resistance. Genomic sequencing technology has been widely applied to predict bacterial resistance in other bacteria, but the catalog of known resistance-determining genes to explain phenotypic resistance in the MABC is incomplete for many antibiotics. Eighty-one MABC strains were isolated from sputum samples of patients with pulmonary disease in the Beijing Chest Hospital. All isolates were tested for minimum inhibitory concentrations (MICs) to eight antibiotics and underwent whole-genome sequencing (WGS). Of the total 81 MABC isolates, six strains exhibited clarithromycin (CLM) resistance by day 3 in culture, but only one (16.7%, 1/6) contained a mutation in the gene. All strains contained the (100.0%, 49/49) polymorphism and exhibited CLM-induced resistance after 14 days in culture. Of the 61 imipenem-resistant strains, 12 (19.7%, 12/61) had mutations in the gene. Although there were four (4.9%) amikacin-resistant, nine (11.1%) linezolid-resistant, eight (9.9%) clofazimine-resistant, 23 (28.4%) bedaquiline-resistant, and 27 (33.3%) cefoxitin-resistant strains, no known mutations associated with resistance to these antibiotics were found. These results suggest that the explanatory power of known resistance genes for clinical MABC resistance is limited and that other unidentified genes or novel resistance mechanisms may be involved.

摘要

复合分枝杆菌(MABC)是一种具有内在多重耐药性的新兴病原体。基因组测序技术已广泛应用于预测其他细菌的耐药性,但用于解释MABC表型耐药性的已知耐药决定基因目录对于许多抗生素来说并不完整。从北京胸科医院肺部疾病患者的痰液样本中分离出81株MABC菌株。所有分离株均检测了对8种抗生素的最低抑菌浓度(MIC),并进行了全基因组测序(WGS)。在总共81株MABC分离株中,6株在培养第3天表现出对克拉霉素(CLM)耐药,但只有1株(16.7%,1/6)在该基因中存在突变。所有菌株均含有该多态性(100.0%,49/49),并在培养14天后表现出CLM诱导的耐药性。在61株对亚胺培南耐药的菌株中,12株(19.7%,12/61)在该基因中存在突变。尽管有4株(4.9%)对阿米卡星耐药、9株(11.1%)对利奈唑胺耐药、8株(9.9%)对氯法齐明耐药、23株(28.4%)对贝达喹啉耐药和27株(33.3%)对头孢西丁耐药的菌株,但未发现与这些抗生素耐药相关的已知突变。这些结果表明,已知耐药基因对临床MABC耐药性的解释能力有限,可能涉及其他未鉴定的基因或新的耐药机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6762/12217466/b1402e77e20a/aac.01847-24.f001.jpg

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