Nahar Lutfun, Hagiya Hideharu, Gotoh Kazuyoshi, Asaduzzaman Md, Otsuka Fumio
Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Department of Infectious Diseases, Okayama University Hospital, Okayama 700-8558, Japan.
J Clin Med. 2024 Jul 18;13(14):4199. doi: 10.3390/jcm13144199.
: Among various carbapenemases, New Delhi metallo-beta-lactamases (NDMs) are recognized as the most powerful type capable of hydrolyzing all beta-lactam antibiotics, often conferring multi-drug resistance to the microorganism. The objective of this review is to synthesize current scientific data on NDM inhibitors to facilitate the development of future therapeutics for challenging-to-treat pathogens. : Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews, we conducted a MEDLINE search for articles with relevant keywords from the beginning of 2009 to December 2022. We employed various generic terms to encompass all the literature ever published on potential NDM inhibitors. : Out of the 1760 articles identified through the database search, 91 met the eligibility criteria and were included in our analysis. The fractional inhibitory concentration index was assessed using the checkerboard assay for 47 compounds in 37 articles, which included 8 compounds already approved by the Food and Drug Administration (FDA) of the United States. Time-killing curve assays (14 studies, 25%), kinetic assays (15 studies, 40.5%), molecular investigations (25 studies, 67.6%), in vivo studies (14 studies, 37.8%), and toxicity assays (13 studies, 35.1%) were also conducted to strengthen the laboratory-level evidence of the potential inhibitors. None of them appeared to have been applied to human infections. : Ongoing research efforts have identified several potential NDM inhibitors; however, there are currently no clinically applicable drugs. To address this, we must foster interdisciplinary and multifaceted collaborations by broadening our own horizons.
在各种碳青霉烯酶中,新德里金属β-内酰胺酶(NDMs)被认为是最强大的类型,能够水解所有β-内酰胺抗生素,常常使微生物具有多重耐药性。本综述的目的是综合目前关于NDM抑制剂的科学数据,以促进针对难治疗病原体的未来疗法的开发。:遵循系统评价和Meta分析的首选报告项目(PRISMA)扩展版的范围综述要求,我们在MEDLINE数据库中检索了从2009年初到2022年12月的相关关键词文章。我们使用了各种通用术语来涵盖所有已发表的关于潜在NDM抑制剂的文献。:通过数据库搜索确定的1760篇文章中,91篇符合纳入标准并被纳入我们的分析。对37篇文章中的47种化合物使用棋盘法评估了分数抑菌浓度指数,其中包括8种已被美国食品药品监督管理局(FDA)批准的化合物。还进行了时间杀菌曲线试验(14项研究,25%)、动力学试验(15项研究,40.5%)、分子研究(25项研究,67.6%)、体内研究(14项研究,37.8%)和毒性试验(13项研究,35.1%),以加强潜在抑制剂的实验室水平证据。它们似乎都未应用于人类感染。:正在进行的研究工作已经确定了几种潜在的NDM抑制剂;然而,目前尚无临床适用的药物。为了解决这个问题,我们必须通过拓宽自己的视野来促进跨学科和多方面的合作。