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实体器官移植后耐更昔洛韦巨细胞病毒感染的流行病学及结局:泰国一家移植中心的经验

Epidemiology and Outcome of Ganciclovir-Resistant Cytomegalovirus Infection After Solid Organ Transplantation: A Single Transplant Center Experience in Thailand.

作者信息

Bruminhent J, Rotjanapan P, Watcharananan S P

机构信息

Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

出版信息

Transplant Proc. 2017 Jun;49(5):1048-1052. doi: 10.1016/j.transproceed.2017.03.053.

Abstract

BACKGROUND

Data on drug-resistant cytomegalovirus (CMV) infection in solid organ transplantation (SOT) are not often reported from resource-limited settings. We aimed to investigate the epidemiology and outcomes of this infection in SOT recipients at our institution.

METHODS

This was a retrospective study conducted from January 2012 to May 2015. We included all SOT recipients who were suspected for drug-resistant CMV infection. Genotypic assay for UL97 gene mutation was analyzed by real-time polymerase chain reaction. Patients were reviewed for demographic data, clinical presentation, virologic data, treatment, and outcomes.

RESULTS

The population consisted of 18 (12 kidney, 6 liver) SOT recipients with a median age of 20 years (interquartile range [IQR], 1-49); 44% were male. Anti-CMV resistance testing was analyzed at a median time of 23 days (IQR, 14-33) after initiation of anti-CMV therapy with a median CMV load of log 3.79 copies/mL (IQR, 3.37-4.58). During a median period of 2 years (IQR, 1-3), 6 SOT recipients were identified with UL97 gene mutation in codon 460, conferring ganciclovir (GCV) resistance. Patients with UL97 gene mutation had a longer mean duration of CMV DNAemia compared with those without mutation (263 vs 107 days; P = .04). All patients received high-dose GCV. Two patients received foscarnet and cidofovir. Two patients died (non-CMV-related), and 4 patients developed opportunistic infections other than CMV.

CONCLUSIONS

GCV-resistant CMV infection in SOT recipients is an emerging clinical problem in resource-limited country. Those with UL97 mutation CMV infection have prolonged duration of CMV DNAemia. Clinicians should be aware of this condition when caring for SOT recipients.

摘要

背景

资源有限地区关于实体器官移植(SOT)中耐药巨细胞病毒(CMV)感染的数据报道较少。我们旨在调查我院SOT受者中这种感染的流行病学情况及结局。

方法

这是一项于2012年1月至2015年5月开展的回顾性研究。我们纳入了所有疑似耐药CMV感染的SOT受者。通过实时聚合酶链反应分析UL97基因突变的基因分型检测。对患者的人口统计学数据、临床表现、病毒学数据、治疗及结局进行了回顾。

结果

研究人群包括18例(12例肾移植、6例肝移植)SOT受者,中位年龄为20岁(四分位间距[IQR],1 - 49岁);44%为男性。抗CMV耐药性检测在开始抗CMV治疗后中位时间为23天(IQR,14 - 33)时进行,中位CMV载量为log 3.79拷贝/毫升(IQR,3.37 - 4.58)。在中位时间为2年(IQR,1 - 3)期间,6例SOT受者被鉴定出密码子460处存在UL97基因突变,导致对更昔洛韦(GCV)耐药。与未发生突变的患者相比,发生UL97基因突变的患者CMV血症的平均持续时间更长(263天对107天;P = 0.04)。所有患者均接受了高剂量GCV治疗。2例患者接受了膦甲酸钠和西多福韦治疗。2例患者死亡(与CMV无关),4例患者发生了除CMV之外的机会性感染。

结论

SOT受者中对GCV耐药的CMV感染在资源有限国家是一个新出现的临床问题。发生UL97突变CMV感染的患者CMV血症持续时间延长。临床医生在诊治SOT受者时应意识到这种情况。

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