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oai:repisalud.isciii.es:20.500.12105/87052025-04-24T18:07:57Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16938col_20.500.12105_16958col_20.500.12105_16961col_20.500.12105_16962col_20.500.12105_16978

00925njm 22002777a 4500 dc López-Aladid, Rubén author Guiu, Alba author Mosquera Gutierrez, Maria del Mar author López-Medrano, Francisco author Cofán, Frederic author Linares, Laura author Torre-Cisneros, Julian author Vidal, Elisa author Moreno, Asunción author Aguado, José María author Cordero, Elisa author Martin-Gandul, Cecilia author Carratalà, Jordi author Sabé, Nuria author Niubó, Jordi author Cervera, Carlos author Capón, Alicia author Cervilla, Anna author Santos, Marta author Bodro, Marta author Muñoz, Patricia author Fariñas, María Carmen author Antón, Andrés author Aranzamendi, Maitane author Montejo, Miguel author Perez-Romero, Pilar author Len, Oscar author Marcos, María Ángeles author 2019 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. PLoS One. 2019 Jul 18;14(7):e0219701. 10.1371/journal.pone.0219701 1932-6203 1932-6203 PloS one 31318908 http://hdl.handle.net/20.500.12105/8705 Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing