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实体器官或干细胞移植后巨细胞病毒感染的管理。当前指南与未来展望。

Management of cytomegalovirus infection after solid-organ or stem-cell transplantation. Current guidelines and future prospects.

作者信息

Hebart H, Kanz L, Jahn G, Einsele H

机构信息

Medizinische Klinik und Poliklinik, Abteilung II, University Hospital, Tübingen, Germany.

出版信息

Drugs. 1998 Jan;55(1):59-72. doi: 10.2165/00003495-199855010-00005.

Abstract

Recent developments in diagnosis and therapy of cytomegalovirus (CMV) infection have helped to reduce CMV-associated mortality following organ transplantation. However, CMV is still associated with significant morbidity in recipients of an allogeneic stem cell or solid-organ transplant. The clinical symptoms of active CMV infection per se and, most importantly, the prevalence of life-threatening CMV disease show broad variation between different patient populations depending on the type of transplant and the intensity of immuno-suppression. Therefore, management of CMV infection must be stratified according to risk profiles of a given patient population. In the past decade, novel diagnostic assays (such as rapid shell-vial culture, polymerase chain reaction, pp65 antigen assay and sensitive hybridisation techniques) have been developed. Broad variations in the ability of a given test to predict a positive or negative risk of developing CMV disease have been observed between different transplant modalities. Highly effective therapeutic agents against CMV, such as ganciclovir and foscarnet, have become available, improving the outcome of patients with CMV disease. Moreover, antiviral prophylaxis with ganciclovir or aciclovir has been shown to reduce CMV infection and CMV disease following organ transplantation. However, these drugs are often associated with considerable toxicity. Moreover, antiviral resistance to ganciclovir and foscarnet has been observed in recipients of organ transplants and, even more frequently, in patients with AIDS. Short courses of pre-emptive antiviral therapy, administered after CMV infection has been documented by sensitive diagnostic techniques prior to the development of clinical symptoms, help to reduce duration and incidence of adverse effects associated with antiviral drugs and are thus an attractive strategy compared with antiviral prophylaxis. Newer options, such as oral ganciclovir, cidofovir, benzimidavir (1263W94) and lobucavir, are currently under investigation and might further improve the management of CMV infection in recipients of solid-organ or stem-cell transplants.

摘要

巨细胞病毒(CMV)感染诊断和治疗方面的最新进展有助于降低器官移植后与CMV相关的死亡率。然而,在同种异体干细胞或实体器官移植受者中,CMV仍与显著的发病率相关。活动性CMV感染本身的临床症状,以及最重要的是,危及生命的CMV疾病的患病率,在不同患者群体之间表现出广泛差异,这取决于移植类型和免疫抑制强度。因此,CMV感染的管理必须根据特定患者群体的风险状况进行分层。在过去十年中,已开发出新型诊断检测方法(如快速空斑试验培养、聚合酶链反应、pp65抗原检测和灵敏杂交技术)。在不同移植方式之间,已观察到特定检测方法预测发生CMV疾病的阳性或阴性风险的能力存在广泛差异。针对CMV的高效治疗药物,如更昔洛韦和膦甲酸钠,已可供使用,改善了CMV疾病患者的预后。此外,已证明用更昔洛韦或阿昔洛韦进行抗病毒预防可降低器官移植后的CMV感染和CMV疾病。然而,这些药物常常伴有相当大的毒性。此外,在器官移植受者中,甚至在艾滋病患者中更频繁地观察到对更昔洛韦和膦甲酸钠的抗病毒耐药性。在通过灵敏诊断技术在临床症状出现之前记录到CMV感染后给予短疗程的抢先抗病毒治疗,有助于减少与抗病毒药物相关的不良反应的持续时间和发生率,因此与抗病毒预防相比是一种有吸引力的策略。较新的选择,如口服更昔洛韦、西多福韦、苯并咪唑韦(1263W94)和洛布卡韦,目前正在研究中,可能会进一步改善实体器官或干细胞移植受者中CMV感染的管理。

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