Bueno Javier, Ramil Carmen, Green Michael
Pediatric Transplantation Unit, Juan Canalejo Hospital, A Coruña, Spain.
Paediatr Drugs. 2002;4(5):279-90. doi: 10.2165/00128072-200204050-00001.
Cytomegalovirus (CMV) is a significant cause of morbidity and mortality following transplantation, especially in the pediatric population, who remain at high risk of primary infection. The availability of effective antiviral therapy has led to dramatic improvements in the outcome of CMV infection in patients undergoing transplantation. In recent years, three major strategies have been developed for the prevention of CMV disease in this population: reduction of risk of viral acquisition or reactivation by management of risk factors; prophylaxis of all 'at-risk' patients using prophylactic strategies for a defined period of time, initiated at or near the time of transplant; and pre-emptive treatment with ganciclovir of selected 'at-risk' patients, guided by either laboratory markers indicative of subclinical infection or the presence of specific risk factors. In general, well designed comparative studies of one or more antiviral agents for the prevention of CMV have not been carried out. While ganciclovir appears to be more effective than aciclovir, its tolerability profile is less optimal. The use of foscarnet avoids myelosuppresions, but is associated with significant nephrotoxicity. Its use should be reserved for patients unable to tolerate ganciclovir or with ganciclovir-resistant CMV disease. Similar to foscarnet, the high frequency of nephrotoxicity associated with the use of cidofovir limits its use to clinical scenarios suggestive of ganciclovir resistance. Newer options, such as valaciclovir and valganciclovir, are currently under investigation and preliminary experience has been promising. Finally, passive immunoprophylaxis has been shown to prevent CMV disease after solid organ transplantation, but its use in bone marrow transplantation is controversial. Essentially, pre-emptive strategies have relied on the quantitation in the peripheral blood of CMV phosphoprotein pp65 antigen and/or the polymerase chain reaction assay. Strict guidelines for the use of those assays as a guide to pre-emptive therapy have not been standardized. Prospective trials comparing pre-emptive therapy using either intravenous or oral ganciclovir, and now oral valganciclovir or valaciclovir, are necessary to determine the relative cost effectiveness and efficacy of these alternative strategies. Finally, it remains controversial as to whether prophylaxis or pre-emptive therapy is the optimal strategy for preventing CMV disease. While a growing body of literature describes these approaches in adult transplant recipients, published experience in children has been much more limited.
巨细胞病毒（CMV）是移植后发病和死亡的重要原因，尤其是在儿科人群中，他们仍面临原发性感染的高风险。有效的抗病毒治疗的出现使接受移植患者的CMV感染结局有了显著改善。近年来，已制定了三种主要策略来预防该人群的CMV疾病：通过管理风险因素降低病毒感染或再激活的风险；对所有“高危”患者在移植时或接近移植时开始使用预防性策略进行一定时期的预防；以及根据指示亚临床感染的实验室指标或特定风险因素的存在，对选定的“高危”患者进行更昔洛韦抢先治疗。一般来说，尚未对一种或多种预防CMV的抗病毒药物进行精心设计的比较研究。虽然更昔洛韦似乎比阿昔洛韦更有效，但其耐受性不太理想。膦甲酸钠的使用可避免骨髓抑制，但与显著的肾毒性相关。其使用应仅限于无法耐受更昔洛韦或患有更昔洛韦耐药CMV疾病的患者。与膦甲酸钠类似，使用西多福韦相关的高频率肾毒性将其使用限制在提示更昔洛韦耐药的临床情况中。新的选择，如伐昔洛韦和缬更昔洛韦，目前正在研究中，初步经验很有前景。最后，被动免疫预防已被证明可预防实体器官移植后的CMV疾病，但在骨髓移植中的使用存在争议。从本质上讲，抢先策略依赖于外周血中CMV磷蛋白pp65抗原的定量和/或聚合酶链反应检测。将这些检测用作抢先治疗指南的严格标准尚未标准化。有必要进行前瞻性试验，比较使用静脉或口服更昔洛韦以及现在的口服缬更昔洛韦或伐昔洛韦的抢先治疗，以确定这些替代策略的相对成本效益和疗效。最后，预防或抢先治疗是否是预防CMV疾病的最佳策略仍存在争议。虽然越来越多的文献描述了这些方法在成人移植受者中的应用，但儿童中的已发表经验要有限得多。
