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Título: | Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing |
Autor: | López-Aladid, Rubén; Guiu, Alba; Mosquera, María Mar; López-Medrano, Francisco; Cofán, Frederic; Linares, Laura; Torre-Cisneros, Julián; Vidal, Elisa; Moreno, Asunción; Aguado, José María; Cordero-Matía, Elisa CSIC ORCID; Martín-Gandul, Cecilia CSIC ORCID; Carratalà, Jordi; Sabé, Nuria; Niubó, Nuria; Cervera, Carlos; Capón, Alicia; Cervilla, Anna; Santos, Marta; Bodro, Marta; Muñoz García, Patricia; Fariñas, María del Carmen; Antón, Andrés; Aranzamendi Zaldumbide, Maitane; Montejo, Miguel; Pérez-Romero, Pilar CSIC ORCID; Len, Óscar; Marcos, María Ángeles | Fecha de publicación: | 18-jul-2019 | Editor: | Public Library of Science | Citación: | PLoS ONE 14(7): e0219701 (2019) | Resumen: | [Objetives] The aim of this study was to identify CMV drug resistance mutations (DRM) in solid organ transplant (SOT) recipients with suspected resistance comparing next-generation sequencing (NGS) with Sanger sequencing and assessing risk factors and the clinical impact of resistance. [Methods] Using Sanger sequencing as the reference method, we prospectively assessed the ability of NGS to detect CMV DRM in the UL97 and UL54 genes in a nationwide observational study from September 2013 to August 2016. [Results] Among 44 patients recruited, 14 DRM were detected by Sanger in 12 patients (27%) and 20 DRM were detected by NGS, in 16 (36%). NGS confirmed all the DRM detected by Sanger. The additional six mutations detected by NGS were present in <20% of the sequenced population, being located in the UL97 gene and conferring high-level resistance to ganciclovir. The presence of DRM by NGS was associated with lung transplantation (p = 0.050), the administration of prophylaxis (p = 0.039), a higher mean time between transplantation and suspicion of resistance (p = 0.038) and longer antiviral treatment duration before suspicion (p = 0.024). However, the latter was the only factor independently associated with the presence of DRM by NGS in the multivariate analysis (OR 2.24, 95% CI 1.03 to 4.87). [Conclusions] NGS showed a higher yield than Sanger sequencing for detecting CMV resistance mutations in SOT recipients. The presence of DRM detected by NGS was independently associated with longer antiviral treatment. |
Versión del editor: | https://doi.org/10.1371/journal.pone.0219701 | URI: | http://hdl.handle.net/10261/201095 | DOI: | 10.1371/journal.pone.0219701 | E-ISSN: | 1932-6203 |
Aparece en las colecciones: | (IBIS) Artículos |
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