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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorLópez-Aladid, Rubén
dc.contributor.authorGuiu, Alba
dc.contributor.authorMosquera, Maria M.
dc.contributor.authorLópez-Medrano, Francisco
dc.contributor.authorCofan-Pujol, Frederic
dc.contributor.authorLinares, Laura
dc.contributor.authorAntón Pagarolas, Andres
dc.contributor.authorLen Abad, Oscar
dc.date.accessioned2020-01-29T07:59:37Z
dc.date.available2020-01-29T07:59:37Z
dc.date.issued2019-07-18
dc.identifier.citationLópez-Aladid R, Guiu A, Mosquera MM, López-Medrano F, Cofán F, Linares L, et al. Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing. PLoS One. 2019;14(7):e0219701.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11351/4564
dc.descriptionAntiviral resistance; Solid organ transplant; Next-generation sequencing
dc.description.abstractOBJETIVES: 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.
dc.language.isoeng
dc.publisherPublic Library of Science
dc.relation.ispartofseriesPLoS One;14(7)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectTrasplantació d'òrgans, teixits, etc
dc.subjectResistència als medicaments
dc.subjectADN - Anàlisi
dc.subject.meshDrug Resistance, Viral
dc.subject.meshSequence Analysis, DNA
dc.subject.meshTransplants
dc.titleImprovement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1371/journal.pone.0219701
dc.subject.decsfarmacorresistencia viral
dc.subject.decsanálisis de secuencias de ADN
dc.subject.decstrasplantes
dc.relation.publishversionhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219701
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.authoraffiliation[López-Aladid R, Guiu A, Mosquera MM] Department of Clinical Microbiology, Hospital Clinic, Universidad de Barcelona, Barcelona, Spain. Institute for Global Health (ISGlobal), Barcelona, Spain. [López-Medrano F] Unit of Infectious Diseases, Instituto de Investigación Hospital 12 Octubre (i + 12), University Hospital 12 de Octubre, Madrid, Spain. Universidad Complutense, Madrid, Spain. [Cofán F] Department of Nephrology and Renal Transplant, Hospital Clinic, Universidad de Barcelona, Barcelona, Spain. [Linares L] Department of Infectious Diseases, Hospital Clinic, Universidad de Barcelona, Barcelona, Spain. Institut d’Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain. [Antón A] Servei de Microbiologia, Hospital Universitari Vall d'Hebron, Barcelona, Spain. [Len O] Servei de Malalties Infeccioses, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain
dc.identifier.pmid31318908
dc.identifier.wos000482340700044
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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