Duncan S R, Grgurich W F, Iacono A T, Burckart G J, Yousem S A, Paradis I L, Williams P A, Johnson B A, Griffith B P
Department of Medicine, University of Pittsburgh, Pennsylvania.
Am J Respir Crit Care Med. 1994 Jul;150(1):146-52. doi: 10.1164/ajrccm.150.1.8025741.
In an attempt to modify the sequelae of cytomegalovirus (CMV) infections after lung transplantation, 25 allograft recipients were randomized to either ganciclovir 5 mg/kg once a day 5 d/wk (Group G) or acyclovir 800 mg four times a day (Group A). All subjects received ganciclovir during postoperative Weeks 1 through 3, and they were then given either A or G regimens until Day 90. At termination of study enrollment, the cumulative incidence of all CMV infections (including seroconversions) was increased in Group A compared with that in Group G (75% versus 15%, p < 0.01), as was the incidence of overt CMV shedding and/or pneumonitis (50% versus 15%, p < 0.043). In comparison with those in Group G, subjects in Group A were also afflicted with an increased prevalence of obliterative bronchiolitis (OB) during the first year after transplantation (54% versus 17%, p < 0.033). Intravenous catheters for ganciclovir administration resulted in four complications among three of the subjects in Group G (23%). The short-term benefits of ganciclovir were ultimately limited, moreover, in that cumulative rates of CMV and prevalence of OB are now similar in both treatment groups after approximately 2 yr of observation. We conclude that prolonged ganciclovir prophylaxis decreases the early incidence of CMV and OB among lung transplant recipients, but these effects are of finite duration. Although CMV prevention appears to have considerable potential value in this population, definitive viral prophylaxis will require development of protracted or repeated treatment regimens, or longer-acting agents.
为了改善肺移植后巨细胞病毒(CMV)感染的后遗症,25例同种异体移植受者被随机分为两组,一组接受更昔洛韦5mg/kg,每天1次,每周5天(G组),另一组接受阿昔洛韦800mg,每天4次(A组)。所有受试者在术后第1至3周接受更昔洛韦治疗,然后给予A组或G组方案直至第90天。在研究入组结束时,A组所有CMV感染(包括血清转化)的累积发生率高于G组(75%对15%,p<0.01),显性CMV脱落和/或肺炎的发生率也是如此(50%对15%,p<0.043)。与G组相比,A组受试者在移植后第一年闭塞性细支气管炎(OB)的患病率也有所增加(54%对17%,p<0.033)。G组中3名受试者因静脉注射更昔洛韦导管出现了4例并发症(23%)。此外,更昔洛韦的短期益处最终是有限的,因为在观察约2年后,两个治疗组的CMV累积发生率和OB患病率现在相似。我们得出结论,延长更昔洛韦预防时间可降低肺移植受者CMV和OB的早期发生率,但这些效果持续时间有限。虽然CMV预防在该人群中似乎具有相当大的潜在价值,但明确的病毒预防将需要开发长期或重复的治疗方案,或作用时间更长的药物。