Revealing the Unseen: Next-Generation Sequencing for Early Detection of Drug-Resistant Cytomegalovirus Variants Upon Letermovir Prophylaxis Failure.

Nägele, Klaudia; Bättig, Veronika; Gosert, Rainer; Walti, Carla S; Prince, Spasenija Savic; Halter, Jörg; Mathews, Roby; Stühler, Claudia et al. · J Infect Dis · 2025

case_report · Level V

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Abstract

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.

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