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Title: Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance
Author: López Aladid, Rubén
Guiu, Alba
Sanclemente, Gemma
López Medrano, Francisco
Cofán Pujol, Federico
Mosquera, M. Mar
Torre-Cisneros, Julián
Vidal, Elisa
Moreno, Asunción
Aguado, Jose Maria
Cordero, Elisa
Martin Gandul, Cecilia
Pérez Romero, Pilar
Carratalà, Jordi
Sabe, Nuria
Niubo, Jordi
Cervera, Carlos
Cervilla, Anna
Bodro, Marta
Munoz, Patricia
Fariñas, Carmen
Codina, M. Gemma
Aranzamendi, Maite
Montejo, Miguel
Len, Oscar
Marcos, Ma. Angeles
Keywords: Citomegalovirus
Trasplantament d'òrgans
Transplantation of organs
Issue Date: 16-Mar-2017
Publisher: Elsevier
Abstract: BACKGROUND: Current guidelines recommend that treatment of resistant cytomegalovirus (CMV) in solid organ transplant (SOT) recipients must be based on genotypic analysis. However, this recommendation is not systematically followed. OBJECTIVES: To assess the presence of mutations associated with CMV resistance in SOT recipients with suspected resistance, their associated risk factors and the clinical impact of resistance. STUDY DESIGN: Using Sanger sequencing we prospectively assessed the presence of resistance mutations in a nation-wide prospective study between September 2013-August 2015. RESULTS: Of 39 patients studied, 9 (23%) showed resistance mutations. All had one mutation in the UL 97 gene and two also had one mutation in the UL54 gene. Resistance mutations were more frequent in lung transplant recipients (44% p=0.0068) and in patients receiving prophylaxis >/=6 months (57% vs. 17%, p=0.0180). The mean time between transplantation and suspicion of resistance was longer in patients with mutations (239 vs. 100days, respectively, p=0.0046) as was the median treatment duration before suspicion (45 vs. 16days, p=0.0081). There were no significant differences according to the treatment strategies or the mean CMV load at the time of suspicion. Of note, resistance-associated mutations appeared in one patient during CMV prophylaxis and also in a seropositive organ recipient. Incomplete suppression of CMV was more frequent in patients with confirmed resistance. CONCLUSIONS: Our study confirms the need to assess CMV resistance mutations in any patient with criteria of suspected clinical resistance. Early confirmation of the presence of resistance mutations is essential to optimize the management of these patients.
Note: Versió postprint del document publicat a:
It is part of: Journal of Clinical Virology, 2017, vol. 90, p. 57-63
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ISSN: 1386-6532
Appears in Collections:Articles publicats en revistes (ISGlobal)

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