dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | López-Aladid, Rubén |
dc.contributor.author | Guiu, Alba |
dc.contributor.author | Mosquera, Maria M. |
dc.contributor.author | López-Medrano, Francisco |
dc.contributor.author | Cofan-Pujol, Frederic |
dc.contributor.author | Linares, Laura |
dc.contributor.author | Antón Pagarolas, Andres |
dc.contributor.author | Len Abad, Oscar |
dc.date.accessioned | 2020-01-29T07:59:37Z |
dc.date.available | 2020-01-29T07:59:37Z |
dc.date.issued | 2019-07-18 |
dc.identifier.citation | López-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.issn | 1932-6203 |
dc.identifier.uri | https://hdl.handle.net/11351/4564 |
dc.description | Antiviral resistance; Solid organ transplant; Next-generation sequencing |
dc.description.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.
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.iso | eng |
dc.publisher | Public Library of Science |
dc.relation.ispartofseries | PLoS One;14(7) |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.source | Scientia |
dc.subject | Trasplantació d'òrgans, teixits, etc |
dc.subject | Resistència als medicaments |
dc.subject | ADN - Anàlisi |
dc.subject.mesh | Drug Resistance, Viral |
dc.subject.mesh | Sequence Analysis, DNA |
dc.subject.mesh | Transplants |
dc.title | Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1371/journal.pone.0219701 |
dc.subject.decs | farmacorresistencia viral |
dc.subject.decs | análisis de secuencias de ADN |
dc.subject.decs | trasplantes |
dc.relation.publishversion | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219701 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
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.pmid | 31318908 |
dc.identifier.wos | 000482340700044 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |