Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing
López-Aladid, Rúben (Barcelona Institute for Global Health (ISGlobal))
Guiu, Alba (Barcelona Institute for Global Health (ISGlobal))
Mosquera, Maria del Mar (Barcelona Institute for Global Health (ISGlobal))
López-Medrano, Francisco (Hospital Universitario 12 de Octubre (Madrid))
Cofan, Frederic (Hospital Clínic i Provincial de Barcelona)
Linares, Laura (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Torre-Cisneros, Julián (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Vidal, Elisa (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Moreno Camacho, Asunción (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Aguado, José María (Hospital Universitario 12 de Octubre (Madrid))
Cordero, Elisa (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Martin-Gandul, Cecilia (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Carratalà, Jordi (Institut d'Investigació Biomèdica de Bellvitge)
Sabé, Núria (Institut d'Investigació Biomèdica de Bellvitge)
Niubó, Jordi (Hospital Universitari de Bellvitge)
Cervera, Carlos (Department of Medicine. Division of Infectious Diseases. University of Alberta)
Capón, Alicia (Barcelona Institute for Global Health (ISGlobal))
Cervilla, Anna (Barcelona Institute for Global Health (ISGlobal))
Santos, Marta (Barcelona Institute for Global Health (ISGlobal))
Bodro, Marta (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Muñoz, Patricia (Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM))
Fariñas, María Carmen (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Antón, Andrés (Hospital Universitari Vall d'Hebron)
Aranzamendi Zaldumbide, Maitane (Hospital Universitario de Cruces (Barakaldo, País Basc))
Montejo, Miguel (Hospital Universitario de Cruces (Barakaldo, País Basc))
Pérez-Romero, Pilar (National Center for Microbiology. Instituto de Salud Carlos III)
Len, Oscar (Hospital Universitari Vall d'Hebron)
Marcos, María Ángeles (Barcelona Institute for Global Health (ISGlobal))
Universitat Autònoma de Barcelona

Data:	2019
Resum:	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.
Ajuts:	Ministerio de Economía y Competitividad PS12-02131 Instituto de Salud Carlos III PIPI17-02150
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cytomegalovirus ; Drug Resistance, Viral ; Female ; Genes, Viral ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Mutation ; Transplant Recipients
Publicat a:	PloS one, Vol. 14 Núm. 7 (2019) , p. e0219701, ISSN 1932-6203

DOI: 10.1371/journal.pone.0219701
PMID: 31318908

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