Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance

作者：Lopez Aladid Ruben; Guiu Alba; Sanclemente Gemma; Lopez Medrano Francisco; Cofan Frederic; Mar Mosquera M; Torre Cisneros Julian; Vidal Elisa; Moreno Asuncion; Maria Aguado Jose; Cordero Elisa; Martin Gandul Cecilia; Perez Romero Pilar; Carratala Jordi; Sabe Nuria; Niubo Jordi; Cervera Carlos; Cervilla Anna; Bodro Marta; Munoz Patricia; Farinas Carmen; Gemma Codina M; Aranzamendi Maitane; Montejo Miguel; Len Oscar; Angeles Marcos M

来源：Journal of Clinical Virology, 2017, 90: 57-63.

DOI：10.1016/j.jcv.2017.03.014

• Cytomegalovirus
• Suspected resistance
• Genotypic analysis
• Solid organ transplantation

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. 100 days, respectively, p = 0.0046) as was the median treatment duration before suspicion (45 vs. 16 days, 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.

• 出版日期2017-5