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Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638921/ https://www.ncbi.nlm.nih.gov/pubmed/31318908 http://dx.doi.org/10.1371/journal.pone.0219701 |
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author | López-Aladid, Rubén Guiu, Alba Mosquera, Maria Mar López-Medrano, Francisco Cofán, Frederic Linares, Laura Torre-Cisneros, Julián Vidal, Elisa Moreno, Asunción Aguado, Jose María Cordero, Elisa Martin-Gandul, Cecilia Carratalá, Jordi Sabé, Nuria Niubó, Jordi Cervera, Carlos Capón, Alicia Cervilla, Anna Santos, Marta Bodro, Marta Muñoz, Patricia Fariñas, Maria Carmen Antón, Andrés Aranzamendi, Maitane Montejo, Miguel Pérez-Romero, Pilar Len, Oscar Marcos, Maria Ángeles |
author_facet | López-Aladid, Rubén Guiu, Alba Mosquera, Maria Mar López-Medrano, Francisco Cofán, Frederic Linares, Laura Torre-Cisneros, Julián Vidal, Elisa Moreno, Asunción Aguado, Jose María Cordero, Elisa Martin-Gandul, Cecilia Carratalá, Jordi Sabé, Nuria Niubó, Jordi Cervera, Carlos Capón, Alicia Cervilla, Anna Santos, Marta Bodro, Marta Muñoz, Patricia Fariñas, Maria Carmen Antón, Andrés Aranzamendi, Maitane Montejo, Miguel Pérez-Romero, Pilar Len, Oscar Marcos, Maria Ángeles |
author_sort | López-Aladid, Rubén |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6638921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-66389212019-07-25 Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing López-Aladid, Rubén Guiu, Alba Mosquera, Maria Mar López-Medrano, Francisco Cofán, Frederic Linares, Laura Torre-Cisneros, Julián Vidal, Elisa Moreno, Asunción Aguado, Jose María Cordero, Elisa Martin-Gandul, Cecilia Carratalá, Jordi Sabé, Nuria Niubó, Jordi Cervera, Carlos Capón, Alicia Cervilla, Anna Santos, Marta Bodro, Marta Muñoz, Patricia Fariñas, Maria Carmen Antón, Andrés Aranzamendi, Maitane Montejo, Miguel Pérez-Romero, Pilar Len, Oscar Marcos, Maria Ángeles PLoS One Research Article 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. Public Library of Science 2019-07-18 /pmc/articles/PMC6638921/ /pubmed/31318908 http://dx.doi.org/10.1371/journal.pone.0219701 Text en © 2019 López-Aladid et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article López-Aladid, Rubén Guiu, Alba Mosquera, Maria Mar López-Medrano, Francisco Cofán, Frederic Linares, Laura Torre-Cisneros, Julián Vidal, Elisa Moreno, Asunción Aguado, Jose María Cordero, Elisa Martin-Gandul, Cecilia Carratalá, Jordi Sabé, Nuria Niubó, Jordi Cervera, Carlos Capón, Alicia Cervilla, Anna Santos, Marta Bodro, Marta Muñoz, Patricia Fariñas, Maria Carmen Antón, Andrés Aranzamendi, Maitane Montejo, Miguel Pérez-Romero, Pilar Len, Oscar Marcos, Maria Ángeles Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing |
title | Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing |
title_full | Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing |
title_fullStr | Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing |
title_full_unstemmed | Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing |
title_short | Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing |
title_sort | improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638921/ https://www.ncbi.nlm.nih.gov/pubmed/31318908 http://dx.doi.org/10.1371/journal.pone.0219701 |
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