Emergence of drug-resistant cytomegalovirus in the era of valganciclovir prophylaxis: therapeutic implications and outcomes
Emergence of drug-resistant cytomegalovirus in the era of valganciclovir prophylaxis: therapeutic implications and outcomes
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DOI：
10.1111/j.1399-0012.2007.00761.x
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发表时间：
2008-03-01
影响因子：
2.1
通讯作者：
Razonable, Raymund R.
中科院分区：
文献类型：
--
作者：
Eid, Albert J.;Arthurs, Supha K.;Razonable, Raymund R.
背景：据报道，缬更昔洛韦预防与更昔洛韦耐药巨细胞病毒（CMV）的发生率较低有关。我们评估了接受缬更昔洛韦预防的实体器官移植患者中耐药 CMV 的发生率、临床特征和结局。方法：对所有 CMV D+/R- 肾脏、胰腺、肝脏和心脏受者的病历进行 CMV 疾病筛查，并回顾耐药 CMV 患者的临床病程和结局。结果：在四年的研究期间，共有 225 名 CMV D+/R- 移植患者接受了 CMV 移植。缬更昔洛韦预防的中位时间为 92 天。 225 名患者中有 65 名 (29%) 出现迟发性原发性 CMV 疾病，其中 9 名 (14%) 疑似患有耐药病毒。四人 (6.2%) 已确认 UL97 或 UL54 突变。除一名患者外，所有患者均表现出胃肠道组织侵袭性疾病。除了减少免疫抑制外，静脉注射膦甲酸联合或不联合 CMV 超免疫球蛋白是最常见的治疗方法。药物相关的肾毒性很常见，并导致两名患者出现同种异体移植物丢失。在平均 2.2 年的随访期间，四分之二的已证实患有耐药 CMV 的患者中发生了同种异体移植物丢失和死亡，五分之三的临床疑似耐药 CMV 患者发生了同种异体移植丢失和死亡。 结论：在接受缬更昔洛韦预防的 CMV D+/R- 实体器官移植患者中，因临床怀疑或基因型证实的耐药 CMV 导致的巨细胞病毒性疾病并不罕见。由于其显着的发病率和死亡率，需要优化 CMV 预防策略，以减少耐药 CMV 对器官移植成功结果的负面影响。
Background: Valganciclovir prophylaxis is reportedly associated with a low incidence of ganciclovir-resistant cytomegalovirus (CMV). We assessed the incidence, clinical features, and outcome of drug-resistant CMV among solid organ transplant patients who received valganciclovir prophylaxis.Methods: The medical records of all CMV D+/R- kidney, pancreas, liver, and heart recipients were screened for CMV disease, and the clinical course and outcomes of patients with drug-resistant CMV were reviewed.Results: During a four-yr-study period, a total of 225 CMV D+/R- transplant patients received valganciclovir prophylaxis for a median of 92 d. Sixty-five (29%) of the 225 patients developed delayed-onset primary CMV disease, including nine (14%) suspected to have drug-resistant virus. Four (6.2%) had confirmed UL97 or UL54 mutations. All except one patient manifested gastrointestinal tissue-invasive disease. Together with reduction in immunosuppression, intravenous foscarnet with or without CMV hyperimmunoglobulin was the most common treatment. Drug-associated nephrotoxicity was commonly observed and resulted in allograft loss in two patients. During the mean follow-up of 2.2 yr, allograft loss and mortality occurred in two of four patients with proven and in three of five patients with clinically suspected drug-resistant CMV.Conclusions: Cytomegalovirus disease because of clinically suspected or genotypically confirmed drug-resistant CMV is not uncommon in CMV D+/R- solid organ transplant patients who received valganciclovir prophylaxis. Because of its significant morbidity and mortality, an optimized strategy of CMV prevention is warranted to reduce the negative impact of drug-resistant CMV on the successful outcome of organ transplantation.