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NitroSpeed坦尼硼巴坦NP试验作为检测β-内酰胺酶介导的对坦尼硼巴坦敏感性的快速试验。

The NitroSpeed Taniborbactam NP test as a rapid test for detection of β-lactamase-mediated susceptibility to taniborbactam.

作者信息

Raro Otávio Hallal Ferreira, Herrera-Espejo Soraya, Bouvier Maxime, Kerbol Auriane, Poirel Laurent, Nordmann Patrice

机构信息

Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland.

Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital/CSIC/University of Seville, 41013 Seville, Spain.

出版信息

FEMS Microbiol Lett. 2025 Jan 10;372. doi: 10.1093/femsle/fnaf044.

DOI:10.1093/femsle/fnaf044
PMID:40328681
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12065395/
Abstract

Taniborbactam (TAN) is an investigational β-lactamase inhibitor in clinical development combined with cefepime for the treatment of bacterial infections caused by broad-spectrum β-lactamase-expressing bacteria. Its spectrum of inhibition encompasses all classes of β-lactamases, including clinically important metallo-β-lactamases (MBLs) NDM-1 and VIM-2. However, TAN lacks a significant inhibition of imipenemase-type β-lactamases. Rare TAN-resistant New Delhi metallo-β-lactamase (NDM) or Verona integron-encoded metallo-β-lactamase (VIM) variants (namely NDM-9, NDM-30, and VIM-83) have been identified. The NitroSpeed Taniborbactam NP test was developed to rapidly assess the β-lactamase inhibitory activity of TAN against various β-lactamases, particularly serving as an efficient tool for identifying compounds with potential activity against different types of MBLs. The test is based on the hydrolysis of (i) nitrocefin (to determine the presence or absence of β-lactamase), (ii) ertapenem (to confirm the presence or the absence of carbapenemase), and (iii) TAN (to assess whether the carbapenemase is inhibited by TAN). The test was validated using a collection of 134 genetically characterized clinical isolates (103 Enterobacterales and 31 Pseudomonas aeruginosa). The NitroSpeed Taniborbactam NP test is simple, easy to perform, and provides results within ≤15 min. When evaluated against a broad set of β-lactamases, the test demonstrated 100% sensitivity, specificity, and accuracy.

摘要

他尼硼巴坦(TAN)是一种处于临床开发阶段的研究性β-内酰胺酶抑制剂,与头孢吡肟联合用于治疗由产广谱β-内酰胺酶的细菌引起的细菌感染。其抑制谱涵盖所有类型的β-内酰胺酶,包括临床上重要的金属β-内酰胺酶(MBL)NDM-1和VIM-2。然而,TAN对亚胺培南酶型β-内酰胺酶缺乏显著抑制作用。已鉴定出罕见的对TAN耐药的新德里金属β-内酰胺酶(NDM)或维罗纳整合子编码金属β-内酰胺酶(VIM)变体(即NDM-9、NDM-30和VIM-83)。开发了NitroSpeed他尼硼巴坦NP试验,以快速评估TAN对各种β-内酰胺酶的β-内酰胺酶抑制活性,特别是作为鉴定对不同类型MBL具有潜在活性的化合物的有效工具。该试验基于(i)硝噻吩(用于确定β-内酰胺酶的存在与否)、(ii)厄他培南(用于确认碳青霉烯酶的存在与否)和(iii)TAN(用于评估碳青霉烯酶是否被TAN抑制)的水解反应。使用134株经基因特征鉴定的临床分离株(103株肠杆菌科细菌和31株铜绿假单胞菌)对该试验进行了验证。NitroSpeed他尼硼巴坦NP试验简单、易于操作,且在≤15分钟内即可得出结果。在针对多种β-内酰胺酶进行评估时,该试验显示出100%的敏感性、特异性和准确性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04bc/12065395/0c13ac7de5ce/fnaf044fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04bc/12065395/0c13ac7de5ce/fnaf044fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04bc/12065395/0c13ac7de5ce/fnaf044fig1.jpg

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本文引用的文献

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Cefepime-Taniborbactam in Complicated Urinary Tract Infection.头孢吡肟-他唑巴坦治疗复杂性尿路感染。
N Engl J Med. 2024 Feb 15;390(7):611-622. doi: 10.1056/NEJMoa2304748.
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The metallo-β-lactamases strike back: emergence of taniborbactam escape variants.金属β-内酰胺酶卷土重来:坦尼硼巴坦逃逸变异体的出现。
Antimicrob Agents Chemother. 2024 Feb 7;68(2):e0151023. doi: 10.1128/aac.01510-23. Epub 2024 Jan 4.
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Structural basis of metallo-β-lactamase resistance to taniborbactam.金属β-内酰胺酶对替加环素耐药的结构基础。
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potency of xeruborbactam in combination with multiple β-lactam antibiotics in comparison with other β-lactam/β-lactamase inhibitor (BLI) combinations against carbapenem-resistant and extended-spectrum β-lactamase-producing .比较 X 型头孢洛巴坦与其他β-内酰胺/β-内酰胺酶抑制剂(BLI)组合对碳青霉烯类耐药和产超广谱β-内酰胺酶的抗菌活性。
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Wide dissemination of Gram-negative bacteria producing the taniborbactam-resistant NDM-9 variant: a One Health concern.产耐替加环素NDM-9变体的革兰氏阴性菌的广泛传播:一个“同一健康”问题
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Deciphering the evolution of metallo-β-lactamases: A journey from the test tube to the bacterial periplasm.解析金属β-内酰胺酶的进化:从试管到细菌周质的旅程。
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National surveillance pilot study unveils a multicenter, clonal outbreak of VIM-2-producing Pseudomonas aeruginosa ST111 in the Netherlands between 2015 and 2017.国家监测试点研究揭示了 2015 年至 2017 年间,荷兰发生了多中心、克隆的 VIM-2 型铜绿假单胞菌 ST111 感染事件。
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