Minor J R, Baltz J K
Pharmacy Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892.
DICP. 1991 Jan;25(1):41-7. doi: 10.1177/106002809102500109.
Cytomegalovirus (CMV), a major opportunistic viral pathogen frequently causing disease in immunocompromised patients such as organ transplant recipients and people with AIDS, may present as pneumonitis, gastrointestinal disease, or encephalitis. Its most common manifestation in patients with AIDS is retinitis which, if left untreated, invariably progresses to extensive retinal necrosis and ultimately to blindness. Ganciclovir sodium, currently the only licensed antiviral agent for the treatment of CMV retinitis, effectively controls this infection in a majority of AIDS patients, but significant granulocytopenia or thrombocytopenia related to ganciclovir therapy often limit its clinical application. Myelosuppression may be further exacerbated in AIDS patients by such other agents as zidovudine or trimethoprim/sulfamethoxazole, often necessitating dosage reductions or discontinuation of these agents in patients receiving ganciclovir. Foscarnet sodium, a pyrophosphate analog active against both cytomegalovirus and the human immunodeficiency virus type 1 (HIV), may be an effective alternative to ganciclovir in the management of CMV retinitis. Trials with intravenous foscarnet in CMV retinitis have reported favorable results using initial daily doses of 180-230 mg/kg/d given as intermittent infusions every eight hours, followed by maintenance regimens of 60-90 mg/kg/d given as single daily one- or two-hour infusions. Foscarnet therapy may result in renal impairment, and indefinite intravenous maintenance therapy may be required to prevent recurrence of CMV infection. Despite these drawbacks, foscarnet's lack of major myelosuppressive toxicity, and its activity in suppressing HIV replication, make this a potentially safe and effective alternative agent for the management of CMV infection, especially in AIDS patients.
巨细胞病毒(CMV)是一种主要的机会性病毒病原体,经常在免疫功能低下的患者中引发疾病,如器官移植受者和艾滋病患者,其可能表现为肺炎、胃肠道疾病或脑炎。它在艾滋病患者中最常见的表现是视网膜炎,如果不进行治疗,视网膜炎必然会发展为广泛的视网膜坏死,最终导致失明。更昔洛韦钠是目前唯一被批准用于治疗CMV视网膜炎的抗病毒药物,它能有效控制大多数艾滋病患者的这种感染,但与更昔洛韦治疗相关的严重粒细胞减少或血小板减少常常限制其临床应用。齐多夫定或甲氧苄啶/磺胺甲恶唑等其他药物可能会使艾滋病患者的骨髓抑制进一步加重,这通常使得接受更昔洛韦治疗的患者必须减少这些药物的剂量或停药。膦甲酸钠是一种焦磷酸盐类似物,对巨细胞病毒和1型人类免疫缺陷病毒(HIV)均有活性,在CMV视网膜炎的治疗中可能是更昔洛韦的有效替代药物。针对CMV视网膜炎进行的静脉注射膦甲酸钠试验报告了良好的结果,初始每日剂量为180 - 230mg/kg/d,每八小时进行一次间歇输注,随后的维持方案为60 - 90mg/kg/d,每日进行一次一至两小时的单次输注。膦甲酸钠治疗可能会导致肾功能损害,并且可能需要进行无限期的静脉维持治疗以预防CMV感染复发。尽管有这些缺点,但膦甲酸钠缺乏主要的骨髓抑制毒性,并且具有抑制HIV复制的活性,这使其成为治疗CMV感染的一种潜在安全有效的替代药物,尤其是在艾滋病患者中。