Revealing the unseen: next generation sequencing for early detection of drug-resistant cytomegalovirus variants upon letermovir prophylaxis failure.

Autor:	Nägele K; Clinical Virology, University Hospital Basel, Basel, Switzerland., Bättig V; Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland., Gosert R; Clinical Virology, University Hospital Basel, Basel, Switzerland., Walti CS; Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland., Prince SS; Institute of Pathology, University Hospital Basel, Basel, Switzerland., Halter J; Division of Hematology, University Hospital Basel, Basel, Switzerland., Mathews R; Division of Hematology, University Hospital Basel, Basel, Switzerland., Stühler C; Infection Biology Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland., Khanna N; Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.; Infection Biology Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland., Leuzinger K; Clinical Virology, University Hospital Basel, Basel, Switzerland.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2024 Aug 30. Date of Electronic Publication: 2024 Aug 30.
DOI:	10.1093/infdis/jiae414
Abstrakt:	In allogeneic hematopoietic cell transplant (HCT)-recipients, prophylactic management strategies are essential for preventing 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 post-HCT despite receiving letermovir prophylaxis. Sanger-sequencing failed to detect drug resistance mutations (DRM) until CMV-pneumonitis developed, revealing a UL56-C325R-DRM linked to high-level letermovir resistance. Retrospective analysis with next-generation-sequencing (NGS) revealed the DRM at a low frequency of 6% two weeks prior to detection by Sanger-sequencing. This study highlights the importance of advanced NGS-methods for early detection of CMV-DRMs, allowing for faster adjustments in antiviral treatment strategies. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze:	MEDLINE
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