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

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

Authors :
Ministerio de Economía y Competitividad (España)
Generalitat de Catalunya
European Commission
Fundació La Marató de TV3
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
Martín-Gandul, Cecilia
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
Len, Óscar
Marcos, María Ángeles
Ministerio de Economía y Competitividad (España)
Generalitat de Catalunya
European Commission
Fundació La Marató de TV3
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
Martín-Gandul, Cecilia
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
Len, Óscar
Marcos, María Ángeles
Publication Year :
2019

Abstract

[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.<br />[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.<br />[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).<br />[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.

Details

Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1286537766
Document Type :
Electronic Resource