Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing

Objectives: 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: Usin...

ver descrição completa

Detalhes bibliográficos
Autores: López Aladid, Rubén, Guiu, Alba, Mosquera, Maria Mar, López Medrano, Francisco, Cofán Pujol, Federico, Linares, Laura, Torre Cisneros, Julián, Vidal, Elisa, Moreno Camacho, Ma. Asunción, Aguado, José María, Cordero, Elisa, Martin Gandul, Cecilia, Carratalà, Jordi, Sabé, Nuria, Niubó, Jordi, Cervera, Carlos, Capón, Alicia, Cervilla, Anna, Santos, Marta, Bodro, Marta, Muñoz, Patricia, Farinas, Maria Carmen, Antón, Andrés, Aranzamendi, Maitane, Montejo, Miguel, Pérez Romero, Pilar, Len, Óscar, Marcos, Ma. Angeles
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2019
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/139039
Acesso em linha:https://hdl.handle.net/2445/139039
Access Level:Acceso aberto
Palavra-chave:Citomegalovirus
Trasplantament hepàtic
Cytomegaloviruses
Hepatic transplantation
Descrição
Resumo:Objectives: 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.

Registros relacionados