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美国一起肾移植受者肺孢子菌肺炎暴发的遗传与流行病学分析。

Genetic and Epidemiologic Analyses of an Outbreak of Pneumocystis jirovecii Pneumonia Among Kidney Transplant Recipients in the United States.

机构信息

Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, Connecticut,USA.

Kidney Transplantation Program, Yale-New Haven Hospital, New Haven, Connecticut, USA.

出版信息

Clin Infect Dis. 2022 Mar 1;74(4):639-647. doi: 10.1093/cid/ciab474.

DOI:10.1093/cid/ciab474
PMID:34017984
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9012955/
Abstract

BACKGROUND

Pneumocystis jirovecii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation.

METHODS

Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP.

RESULTS

Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP.

CONCLUSIONS

Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions.

摘要

背景

肺孢子菌是一种机会性真菌,会导致免疫功能低下宿主发生肺孢子菌肺炎(PCP)。在过去 11 个月中,我们观察到肾移植受者(KTR)中 PCP 病例增加,促使我们进行了暴发调查。

方法

收集了 2019 年 7 月至 2020 年 5 月期间诊断为 PCP 的 KTR 的临床和流行病学数据。采用限制性片段长度多态性分析和多位点序列分型联合下一代测序对肺孢子菌株型进行了分型。绘制了传播图,并进行了病例对照分析,以确定与 PCP 相关的危险因素。

结果

19 例 KTR 被诊断为 PCP,中位数为移植后 79 个月;8 例接受每月贝利尤单抗输注。贝利尤单抗组和其他方案组的 KTR 基线特征相似;在研究期间,贝利尤单抗组的就诊次数略多(中位数 7.5 次 vs 3 次)。9 例患者的呼吸道标本分子分型显示,每位患者最多合并感染 7 株肺孢子菌。传播图提示存在人际间多次传播簇。在单变量病例对照分析中,贝利尤单抗、绝对淋巴细胞计数较低、非白种人种族和更多的移植门诊就诊与 PCP 风险增加相关。在多变量和预测能力估计分析中,频繁的门诊就诊是 PCP 的最强危险因素。

结论

就诊次数增加似乎促进了 KTR 中医院获得性 PCP 的多次传播簇。贝利尤单抗是 PCP 的一个危险因素,可能通过每月输注需要频繁就诊而增加就诊次数。

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