López-Aladid Rubén, Guiu Alba, Sanclemente Gemma, López-Medrano Francisco, Cofán Frederic, Mosquera M Mar, Torre-Cisneros Julián, Vidal Elisa, Moreno Asunción, Aguado Jose Maria, Cordero Elisa, Martin-Gandul Cecilia, Pérez-Romero Pilar, Carratalá Jordi, Sabé Nuria, Niubó Jordi, Cervera Carlos, Cervilla Anna, Bodro Marta, Muñoz Patricia, Fariñas Carmen, Codina M Gemma, Aranzamendi Maitane, Montejo Miguel, Len Oscar, Marcos M Angeles
Department of Clinical Microbiology, Hospital Clinic, Universidad de Barcelona, Barcelona Institute for Global Health, Barcelona, (ISGlobal), Spain.
Department of Infectious Diseases, Hospital Clinic, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain.
J Clin Virol. 2017 May;90:57-63. doi: 10.1016/j.jcv.2017.03.014. Epub 2017 Mar 21.
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.
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.
Using Sanger sequencing we prospectively assessed the presence of resistance mutations in a nation-wide prospective study between September 2013-August 2015.
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.
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.
当前指南建议，实体器官移植（SOT）受者中耐药巨细胞病毒（CMV）的治疗必须基于基因型分析。然而，这一建议并未得到系统遵循。
评估疑似耐药的SOT受者中与CMV耐药相关的突变的存在情况、其相关危险因素以及耐药的临床影响。
在2013年9月至2015年8月的一项全国性前瞻性研究中，我们使用桑格测序法前瞻性地评估了耐药突变的存在情况。
在研究的39例患者中，9例（23%）显示出耐药突变。所有患者在UL97基因中有一个突变，其中2例在UL54基因中也有一个突变。耐药突变在肺移植受者中更为常见（44%，p=0.0068），在接受预防治疗≥6个月的患者中也更为常见（57%对17%，p=0.0180）。发生突变的患者从移植到疑似耐药的平均时间更长（分别为239天和10天，p=0.0046），疑似耐药前的中位治疗持续时间也更长（45天对16天，p=0.0081）。根据治疗策略或疑似耐药时的平均CMV载量，未发现显著差异。值得注意的是，一名患者在CMV预防期间以及一名血清学阳性的器官受者中出现了耐药相关突变。确诊耐药的患者中，CMV未得到完全抑制的情况更为常见。
我们的研究证实，对于任何有疑似临床耐药标准的患者，都有必要评估CMV耐药突变。早期确认耐药突变的存在对于优化这些患者的管理至关重要。
