University of Wisconsin-Madison School of Pharmacy, Madison, Wisconsin.
Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, Wisconsin.
Pharmacotherapy. 2017 Oct;37(10):1258-1271. doi: 10.1002/phar.1987. Epub 2017 Sep 3.
Ganciclovir-resistant cytomegalovirus (GR-CMV) is emerging as a significant infection in the abdominal transplant population. GR-CMV is difficult to manage, and treatment options are limited. We report a descriptive case series of 15 patients who had documented GR-CMV at our center and review the literature on treatment of GR-CMV. The first case in this series was detected in 2012; the majority of cases occurred after January 1, 2014, with approximately 50% occurring in 2015. UL97 and UL54 viral genome mutations were present in 100% and 40% of CMV-infected patients, respectively. GR-CMV infection occurred ≤ 1 year posttransplantation in 11 patients (73%). All patients experienced dose reduction of valganciclovir (the oral prodrug of ganciclovir) before the development of GR-CMV. Initial treatment for GR-CMV included a variety of regimens, all including reduction in maintenance immunosuppression. Of the 6 patients with detectable GR-CMV by polymerase chain reaction (PCR) who were discharged without GR-CMV treatment and had a length of stay (LOS) less than 14 days, 83% were subsequently readmitted for treatment of GR-CMV within 2 months (60% in < 20 days); none received leflunomide. Of six patients with a LOS ≥ 14 days, 80% had CMV PCR below quantification on hospital discharge, and only one patient was readmitted in less than 20 days; 83% received leflunomide. Following GR-CMV, there was a 50% rejection incidence, 27% graft loss, and 20% mortality. For patients with more than three admissions for GR-CMV treatment, 100% had a major complication: 60% rejection, 20% graft loss, and 40% mortality. Common clinical characteristics of patients with GR-CMV included high-risk serostatus, lymphocyte depletion, and history of valganciclovir dose reduction. Overall, outcomes were poor. It appears that hospital readmission rate was reduced when CMV was treated to negativity with an initial treatment regimen of reduced immunosuppression, foscarnet, intravenous immunoglobulins, and leflunomide.
巨细胞病毒（CMV）耐药株（GR-CMV）在腹部移植人群中已成为一种重要的感染。GR-CMV 难以治疗，且治疗选择有限。我们报告了 15 例在本中心确诊为 GR-CMV 的患者的描述性病例系列，并回顾了关于 GR-CMV 治疗的文献。该系列中的首例病例于 2012 年检出；大多数病例发生在 2014 年 1 月 1 日之后，其中约 50%发生在 2015 年。100%的 CMV 感染患者存在 UL97 和 UL54 病毒基因组突变，40%的患者存在 UL54 病毒基因组突变。11 例（73%）患者的 GR-CMV 感染发生在移植后 1 年内。所有患者在发生 GR-CMV 之前均经历了缬更昔洛韦（更昔洛韦的口服前体药物）剂量减少。GR-CMV 的初始治疗包括多种方案，均包括降低维持性免疫抑制。6 例可检测到聚合酶链反应（PCR）的 GR-CMV 的患者出院时未接受 GR-CMV 治疗且住院时间（LOS）少于 14 天，83%在 2 个月内因 GR-CMV 再次入院（60%在 20 天内）；无患者接受来氟米特治疗。6 例 LOS≥14 天的患者中，80%在出院时 CMV-PCR 低于定量，仅 1 例在 20 天内再次入院；83%接受来氟米特治疗。GR-CMV 后，排斥反应发生率为 50%，移植物丢失率为 27%，死亡率为 20%。对于因 GR-CMV 治疗而住院超过 3 次的患者，100%发生严重并发症：60%排斥反应、20%移植物丢失和 40%死亡率。GR-CMV 患者的共同临床特征包括高危血清状态、淋巴细胞耗竭和缬更昔洛韦剂量减少史。总体而言，预后较差。似乎当最初的治疗方案采用降低免疫抑制、膦甲酸、静脉注射免疫球蛋白和来氟米特治疗使 CMV 转阴时，医院再入院率降低。
