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preemptive 与序贯预防性-抢先治疗方案在肾移植中治疗巨细胞病毒:治疗失败和抗病毒耐药的比较。

Preemptive versus sequential prophylactic-preemptive treatment regimens for cytomegalovirus in renal transplantation: comparison of treatment failure and antiviral resistance.

机构信息

Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Transplantation. 2010 Feb 15;89(3):320-6. doi: 10.1097/TP.0b013e3181bc0301.

DOI:10.1097/TP.0b013e3181bc0301
PMID:20145523
Abstract

BACKGROUND

Cytomegalovirus (CMV) infections after transplantation are commonly treated using a prophylactic or preemptive regimen with (val)ganciclovir. It remains unclear, which approach is most effective in preventing CMV disease in D+R- patients. The aim of this retrospective study was to compare the treatment response and antiviral resistance in CMV infections between two treatment regimens in D+R- renal transplant recipients.

METHODS

Before 2006, a preemptive treatment regimen with valganciclovir was applied (42 patients). From 2006 onwards, patients first received prophylaxis with valganciclovir for 90 days, followed by a preemptive regimen (29 patients). CMV infections were monitored by regular determination of the CMV DNA load in plasma. Patient charts were reviewed for antiviral treatment data, and resistance was analyzed by nucleotide sequence analysis of the UL97 and UL54 genes in CMV DNA-positive samples.

RESULTS

Treatment failure, defined as a CMV DNA load more than or equal to 1000 copies/mL after at least 2 weeks of treatment, occurred less frequently in the prophylaxis cohort than in the preemptive cohort (14% vs. 71%, P<0.001). No CMV end-organ disease occurred in either cohort. Resistant viral isolates were found during treatment in one patient in the prophylaxis cohort versus in three patients in the preemptive group. All CMV infections with resistant virus were cleared without switch of (val)ganciclovir treatment.

CONCLUSIONS

Treatment failure of CMV infections occurred less frequently in D+R- renal transplant patients on a sequential prophylaxis-preemptive regimen than in patients on a purely preemptive regimen. Antiviral resistance was observed infrequently and apparently played a minor role in treatment failure.

摘要

背景

移植后巨细胞病毒(CMV)感染通常采用预防性或抢先治疗方案,使用(val)更昔洛韦。目前尚不清楚哪种方法在预防 D+R-患者的 CMV 疾病方面最有效。本回顾性研究的目的是比较两种治疗方案在 D+R-肾移植受者 CMV 感染中的治疗反应和抗病毒耐药性。

方法

2006 年之前,采用抢先治疗方案(val)更昔洛韦(42 例)。从 2006 年开始,患者首先接受(val)更昔洛韦 90 天的预防治疗,然后采用抢先治疗方案(29 例)。通过定期检测血浆中 CMV DNA 载量监测 CMV 感染。回顾患者病历以获取抗病毒治疗数据,并通过分析 CMV DNA 阳性样本中 UL97 和 UL54 基因的核苷酸序列来分析耐药性。

结果

治疗失败定义为治疗至少 2 周后 CMV DNA 载量≥1000 拷贝/ml,预防组的发生率明显低于抢先组(14%比 71%,P<0.001)。两组均未发生 CMV 终末器官疾病。在预防组中,有 1 例患者在治疗过程中发现耐药病毒株,而抢先组中有 3 例患者。所有耐药病毒引起的 CMV 感染均在不更换(val)更昔洛韦治疗的情况下清除。

结论

与单纯抢先治疗方案相比,序贯预防-抢先治疗方案在 D+R-肾移植患者中 CMV 感染的治疗失败发生率较低。抗病毒耐药性观察到的频率较低,显然在治疗失败中作用较小。

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