Background

Cytomegalovirus (CMV) infection and development of CMV drug resistance can cause significant morbidity and mortality in patients with lung transplantation (LTX). We investigated the incidence of CMV drug resistance in adult patients with LTX and characterized this patient group and its outcomes.

Methods

We analyzed a single-center retrospective cohort of 735 patients who received LTX between January 2012 and October 2017. We assessed the incidences of CMV UL97 and UL54 genotyping for clinically suspected drug resistance and confirmed drug resistance. Case-matched controls (3 control patients for each resistant patient) were identified by matching for CMV serological status, development of CMV disease or significant viremia (≥3,000 IU/ml), and transplantation date.

Results

The incidence of drug-resistant CMV was 1.98% (11/556) in donor and/or recipient CMV-positive patients and 4.7% (7/150) in donor-positive/recipient-negative patients. Altogether, 27 patients were tested for drug resistance, and 11 strains were resistant, 8 sensitive, and 8 inconclusive. No differences in immunosuppression, acute rejection, or pre-transplant sensitization were seen between case-matched groups. The peak CMV viral load and mean duration of viremia were significantly higher in the resistant group (324,000 vs. 117,000 mean IU/ml, p = 0.048 and 140 vs. 55 days, p < 0.001, respectively). The resistant group had increased overall mortality after onset of viremia compared with controls (3-year mortality 70% vs. 30%; p = 0.01).

Conclusions

Drug-resistant CMV infection is rare, but patients who develop it have decreased overall survival. Peak CMV viral load and duration of CMV viremia were associated with development of resistant CMV infection.

中文翻译：

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肺移植后的耐药性巨细胞病毒感染：发病率，特征和临床结果。

背景

巨细胞病毒（CMV）感染和CMV耐药性的发展可导致肺移植（LTX）患者的明显发病率和死亡率。我们调查了成年LTX患者CMV耐药性的发生率，并对该患者群及其结果进行了表征。

方法

我们分析了2012年1月至2017年10月间接受LTX治疗的735例患者的单中心回顾性队列研究。我们评估了CMV UL97和UL54基因分型的临床可疑耐药性发生率，并确定了耐药性。通过匹配CMV血清学状态，CMV疾病或显着病毒血症（≥3,000 IU / ml）和移植日期来确定病例匹配的对照（每个耐药患者3例对照患者）。

结果

供体和/或受体CMV阳性患者的耐药性CMV发生率为1.98％（11/556），供体阳性/受体阴性患者的耐药性为4.7％（7/150）。总共对27例患者进行了耐药性测试，其中11株耐药，8例敏感，8例不确定。病例匹配组之间在免疫抑制，急性排斥反应或移植前敏化方面没有差异。耐药组的最高CMV病毒载量和平均病毒血症持续时间显着更高（分别为324,000 vs. 117,000，平均IU / ml，p  = 0.048和140 vs. 55天，p <0.001）。与对照组相比，抗药组在病毒血症发作后的总死亡率增加了（3年死亡率分别为70％和30％；p  = 0.01）。

结论

耐药性CMV感染很少见，但发展为它的患者的总生存期却降低了。CMV病毒载量峰值和CMV病毒血症持续时间与耐药性CMV感染的发生有关。