Transplant Department, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
Transpl Infect Dis. 2022 Feb;24(1):e13733. doi: 10.1111/tid.13733. Epub 2021 Oct 5.
Cytomegalovirus (CMV) disease caused by genetically resistant CMV poses a major challenge in solid organ transplant recipients, and the development of resistance is associated with increased morbidity and mortality. Antiviral resistance affects 5%-12% of patients following ganciclovir (GCV) therapy, but is more common in individuals with specific underlying risk factors. These include the CMV D+R- serostatus, type of transplanted organ, dose and duration of (Val)GCV ([V]GCV) prophylaxis, peak viral loads, and the intensity of immunosuppressive therapy. Guideline recommendations for the management of GCV resistance (GanR) in solid organ transplant recipients are based on expert opinion as there is a lack of data from controlled trials. Second-line options to treat GanR include foscarnet (FOS) and cidofovir (CDV), but these drugs are often poorly tolerated due to high rates of toxicity, such as renal dysfunction and neutropenia. Here, we report seven cardiothoracic transplant recipients with GCV resistance CMV infection from our centre treated with CMV immunoglobulin (CMVIG) +/- leflunomide (LEF) and reviewed the literature on the use of these agents in this therapeutic setting.
巨细胞病毒（CMV）疾病由遗传耐药 CMV 引起，这对实体器官移植受者构成重大挑战，而耐药性的发展与发病率和死亡率的增加相关。抗病毒耐药性影响 5%-12%接受更昔洛韦（GCV）治疗的患者，但在具有特定潜在危险因素的个体中更为常见。这些因素包括 CMV D+R-血清状态、移植器官类型、（Val）GCV([V]GCV)预防的剂量和持续时间、病毒载量峰值以及免疫抑制治疗的强度。由于缺乏对照试验的数据，因此，实体器官移植受者 GCV 耐药（GanR）管理的指南建议基于专家意见。治疗 GanR 的二线选择包括膦甲酸（FOS）和更昔洛韦（CDV），但由于毒性发生率高，如肾功能障碍和中性粒细胞减少，这些药物往往难以耐受。在这里，我们报告了来自我们中心的 7 例接受 GCV 耐药 CMV 感染的心胸移植受者，他们接受了 CMV 免疫球蛋白（CMVIG）+/-来氟米特（LEF）治疗，并回顾了这些药物在这种治疗环境中的应用文献。
