In recipients of allogeneic hematopoietic cell transplant, prophylactic management strategies are essential for preventing cytomegalovirus (CMV) reactivation and associated disease. We report on a 63-year-old male patient with a D−/R+ CMV serostatus, who showed ongoing low-level CMV replication after hematopoietic cell transplant despite receiving letermovir prophylaxis. Sanger sequencing failed to detect drug resistance mutations (DRMs) until CMV pneumonitis developed, revealing a UL56-C325R DRM linked to high-level letermovir resistance. Retrospective analysis with next-generation sequencing revealed the DRM at a low frequency of 6% two weeks prior to detection by Sanger sequencing. This study highlights the importance of advanced next-generation sequencing methods for early detection of CMV DRMs, allowing for faster adjustments in antiviral treatment strategies.

中文翻译：

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揭示看不见的事物：用于莱特莫韦预防失败后耐药巨细胞病毒变异的早期检测的下一代测序


在同种异体造血细胞移植的受者中，预防性管理策略对于预防巨细胞病毒 （CMV） 再激活和相关疾病至关重要。我们报告了一名 63 岁男性 D-/R+ CMV 血清状态患者，尽管接受了莱特莫韦预防治疗，但该患者在造血细胞移植后仍显示出持续的低水平 CMV 复制。Sanger 测序未能检测到耐药突变 （DRM），直到 CMV 肺炎发生，揭示了 UL56-C325R DRM 与高水平的莱特莫韦耐药性有关。使用下一代测序进行的回顾性分析显示，在通过 Sanger 测序检测到前 2 周，DRM 的频率较低，为 6%。本研究强调了先进的下一代测序方法对早期检测 CMV DRM 的重要性，从而可以更快地调整抗病毒治疗策略。