دورية أكاديمية
Development and dynamics of cytomegalovirus UL97 ganciclovir resistance mutations in transplant recipients detected by next-generation sequencing
| العنوان: | Development and dynamics of cytomegalovirus UL97 ganciclovir resistance mutations in transplant recipients detected by next-generation sequencing |
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| المؤلفون: | Lodding, Isabelle P., Jørgensen, Mette, Bennedbæk, Marc, Kirkby, Nikolai, Naegele, Klaudia, Gustafsson, Finn, Perch, Michael, Rasmussen, Allan, Sengeløv, Henrik, Sørensen, Søren S., Hirsch, Hans H., Lundgren, Jens D. |
| المصدر: | Lodding , I P , Jørgensen , M , Bennedbæk , M , Kirkby , N , Naegele , K , Gustafsson , F , Perch , M , Rasmussen , A , Sengeløv , H , Sørensen , S S , Hirsch , H H & Lundgren , J D 2021 , ' Development and dynamics of cytomegalovirus UL97 ganciclovir resistance mutations in transplant recipients detected by next-generation sequencing ' , Open Forum Infectious Diseases , vol. 8 , no. 10 , ofab462 . https://doi.org/10.1093/ofid/ofab462Test |
| سنة النشر: | 2021 |
| المجموعة: | University of Copenhagen: Research / Forskning ved Københavns Universitet |
| مصطلحات موضوعية: | Cytomegalovirus, Ganciclovir resistance, Hematopoietic stem cell transplantation, Next-generation sequencing, Solid organ transplantation |
| الوصف: | Background: (Val)ganciclovir resistance mutations in CMV UL97 (UL97-GCV-R) complicate anti-CMV therapy in recipients of solid organ and hematopoietic stem cell transplants, but comprehensive data on prevalence, emergence, and outcome are scarce. Methods: Using next-generation sequencing (NGS; Illumina MiSeq platform), we analyzed UL97-GCV-R in patients with available plasma samples and refractory CMV replication/DNAemia (n = 87) containing viral loads ≥910 IU/mL. Twenty-one patients with CMV DNAemia resolving under antiviral therapy were analyzed as controls. Detected mutations were considered induced and of potential clinical significance if they increased by ≥10% compared with the first detected frequency or if they had a maximum frequency ≥25%. Results: Nineteen of 87 (21.8%) with refractory CMV replication had ≥1 UL97-GCV-R detected by NGS, in comparison to 0/21 of the controls (P = .02). One-third of the recipients had 2 or more induced UL97-GCV-R mutations. The most frequently induced mutations affected codons 595 (42% [8/19]), 594 (32% [6/19]), and 603 (32% [6/19]). C592G was present in all episodes of both cases and controls at frequencies <15%, but never induced. UL97-GCV-R tended to be more frequent in donor/recipient CMV immunoglobulin G mismatch or following failure to complete primary prophylaxis, and many developed invasive CMV disease. Conclusions: UL97-GCV-R is common among transplant patients with refractory CMV replication. Early testing by NGS allows for identification of major mutations at codons 595, 594, and 603 and excludes a major role of C592G in ganciclovir resistance. Large prospective studies on UL97-GCV-R are warranted. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1093/ofid/ofab462 |
| الإتاحة: | https://doi.org/10.1093/ofid/ofab462Test https://curis.ku.dk/portal/da/publications/development-and-dynamics-of-cytomegalovirus-ul97-ganciclovir-resistance-mutations-in-transplant-recipients-detected-by-nextgeneration-sequencingTest(87ebae97-35e4-48a9-b95b-2a7d8f4084a6).html https://curis.ku.dk/ws/files/286313668/ofab462.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.33728631 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/ofid/ofab462 |
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