Forensic DNA Division, National Forensic Service Seoul Institute, Seoul, Republic of Korea.
Seoul National University Biomedical Informatics (SNUBI), Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Front Cell Infect Microbiol. 2024 Aug 29;14:1379790. doi: 10.3389/fcimb.2024.1379790. eCollection 2024.
The decreasing eradication rate is primarily attributed to antibiotic resistance, and further exacerbated by uniform drug administration disregarding a host's metabolic capability. Consequently, applying personalized treatment based on antibiotic resistance-associated variants and the host's metabolic phenotype can potentially increase the eradication rate.
A custom next-generation sequencing panel for personalized eradication treatment (NGS-PHET) was designed which targeted the regions for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin-resistance in and human proton-pump inhibitor (PPI) metabolism. The libraries were constructed following customized methods and sequenced simultaneously. The customized framework criteria, grounded in previously reported antibiotic resistance associated variants and the host's PPI metabolism, was applied to the NGS-PHET results and suggested a personalized treatment for each subject, which was validated through each subject's actual eradication outcome.
Both previously reported and novel variants were identified from sequencing results. Concurrently, five homozygous extensive metabolizers and three intermediate metabolizers were identified. Among the total of 12 subjects, clarithromycin triple therapy was suggested for five subjects, bismuth quadruple therapy was suggested for six subjects, and rifabutin triple therapy was suggested for one subject by following the customized framework criteria. The treatment suggestion for nine of the 12 subjects was consistent with the treatment that each subject achieved eradication with.
Applying the methodology using the NGS-PHET and customized framework helps to perform eradication treatment quickly and effectively in most patients with antibiotic-resistant strains, and is also useful in research to find novel antibiotic-resistance candidates.
根除率的降低主要归因于抗生素耐药性，而统一的药物管理不考虑宿主的代谢能力进一步加剧了这一问题。因此，基于抗生素耐药相关变异和宿主代谢表型应用个体化治疗可能会提高根除率。
设计了一种用于个体化根除治疗的定制下一代测序（NGS-PHET）面板，该面板靶向了与阿莫西林、克拉霉素、甲硝唑、四环素和左氧氟沙星耐药相关的区域，以及人类质子泵抑制剂（PPI）代谢。采用定制方法构建文库，并同时进行测序。定制的框架标准基于先前报道的抗生素耐药相关变异和宿主的 PPI 代谢，应用于 NGS-PHET 结果，并为每位受试者提供了个体化治疗建议，该建议通过每位受试者的实际根除结果进行验证。
从 测序结果中既鉴定出了先前报道的变异，也鉴定出了新的变异。同时，鉴定出了五个 纯合子强代谢者和三个 中间代谢者。在总共 12 名受试者中，根据定制框架标准，建议五名受试者采用克拉霉素三联疗法，六名受试者采用铋四联疗法，一名受试者采用利福布汀三联疗法。12 名受试者中有 9 名的治疗建议与每位受试者实际根除的治疗建议一致。
应用 NGS-PHET 和定制框架的方法有助于在大多数具有抗生素耐药 菌株的患者中快速有效地进行根除治疗，并且在寻找新的抗生素耐药候选药物的研究中也很有用。
