Dual Resistance to Maribavir and Ganciclovir in Transplant Recipients.

IF 3.8 3区医学 Q2 VIROLOGY

Viruses-Basel Pub Date : 2025-03-14 DOI:10.3390/v17030421

Steven B Kleiboeker

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引用次数: 0

Abstract

Background: Human cytomegalovirus (CMV) remains an important pathogen, especially for immunocompromised patients such as solid organ and hematopoietic stem cell recipients. Viral genomic mutations conferring drug resistance are an important impediment to effective CMV management and frequently lead to use of alternative antiviral drugs to treat CMV disease.

Methods: Results from 1459 de-identified patient samples with both UL54 and UL97 sequencing results were analyzed for ganciclovir (GCV) and maribavir (MBV) resistance mutations. Genomic sequencing was performed by the Sanger method and resistance mutations were identified by comparison to CMV reference strain AD169.

Results: Ganciclovir resistance was identified in 379 of 1459 (25.98%) of the samples tested, with most resistance-conferring mutations present in viral gene UL97. A total of 121 of 1459 (8.29%) samples had MBV resistance mutations, and 84 (69.42%) of the 121 samples with MBV resistance also had GCV resistance mutations. Of the 84 samples with resistance to both MBV and GCV, 35 (41.67%) had a single UL97 mutation conferring resistance to both drugs, either C480F or F342Y. The overall prevalence of C480F was increased relative to an earlier analysis of samples from this reference laboratory.

Conclusions: Although a high prevalence of CMV resistance mutations was identified, this must be taken in the context of healthcare providers submitting samples from patients with suspected CMV resistance. Most MBV-resistant samples were also resistant to GCV, suggesting that use of MBV as an alternative to GCV may benefit from genotypic resistance testing to achieve the effective control of CMV disease.

查看原文本刊更多论文

移植受者对马里巴韦和更昔洛韦的双重耐药。

背景：人巨细胞病毒（CMV）仍然是一种重要的病原体，特别是对于免疫功能低下的患者，如实体器官和造血干细胞受体。具有耐药性的病毒基因组突变是有效管理巨细胞病毒的重要障碍，并经常导致使用替代抗病毒药物来治疗巨细胞病毒疾病。方法：对1459份同时具有UL54和UL97测序结果的去鉴定患者样本进行更昔洛韦（GCV）和马里巴韦（MBV）耐药突变分析。采用Sanger法进行基因组测序，并与CMV参考菌株AD169进行比较，鉴定抗性突变。结果：1459份检测样本中有379份（25.98%）被鉴定出更昔洛韦耐药，大多数耐药突变存在于病毒基因UL97。1459份样本中有121份（8.29%）发生MBV耐药突变，其中84份（69.42%）同时发生GCV耐药突变。在84例同时对MBV和GCV耐药的样本中，35例（41.67%）具有单一UL97突变，同时对C480F或F342Y两种药物耐药。C480F的总体流行率相对于早先对该参考实验室样本的分析有所增加。结论：虽然发现了巨细胞病毒耐药突变的高发率，但在医疗保健提供者提交疑似巨细胞病毒耐药患者的样本时，必须考虑到这一点。大多数MBV耐药样本也对GCV耐药，这表明使用MBV作为GCV的替代品可能受益于基因型耐药检测，从而实现对CMV疾病的有效控制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Viruses-Basel VIROLOGY-

CiteScore

7.30

自引率

12.80%

发文量

2445

审稿时长

1 months

期刊介绍： Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.