PDF(Pubmed)
Abstract：
UNASSIGNED: This study characterizes the clinical utility and validity of the Karius test (KT), a plasma microbial cell-free DNA sequencing platform, as an infection surveillance tool among hematopoietic stem cell transplant (HCT) recipients, including monitoring for cytomegalovirus (CMV) and detecting infections relative to standard microbiologic testing (SMT).
UNASSIGNED: A prospective, observational cohort study was performed among adult HCT recipients as inpatients and outpatients. Serial KTs were performed starting with 1 sample within 14 days before HCT, then weekly from 7-63 days posttransplant then monthly from 3-12 months post-HCT. Diagnostic performance of KT versus CMV polymerase chain reaction was evaluated with positive percent agreement and negative percent agreement. Infectious events (<12 months post-HCT) were extracted from medical records. For infectious events without positive SMT, 2 clinicians adjudicated KT results to determine if any detections were a probable cause. Difference in time from KT pathogen detection and infection onset was calculated.
UNASSIGNED: Of the 70 participants, mean age was 49.9 years. For CMV surveillance, positive percent agreement was 100% and negative percent agreement was 90%. There was strong correlation between CMV DNA and KT molecules per microliter (r 2: 0.84, P < .001). Of the 32 SMT+/KT+ infectious events, KT identified 26 earlier than SMT (median: -12 days) and an additional 5 diagnostically difficult pathogens identified by KT but not SMT.
UNASSIGNED: KT detected CMV with high accuracy and correlation with quantitative polymerase chain reaction. Among infectious events, KT demonstrated additive clinical utility by detecting pathogens earlier than SMT and those not detected by SMT.
UNASSIGNED: A prospective, observational cohort study was performed among adult HCT recipients as inpatients and outpatients. Serial KTs were performed starting with 1 sample within 14 days before HCT, then weekly from 7-63 days posttransplant then monthly from 3-12 months post-HCT. Diagnostic performance of KT versus CMV polymerase chain reaction was evaluated with positive percent agreement and negative percent agreement. Infectious events (<12 months post-HCT) were extracted from medical records. For infectious events without positive SMT, 2 clinicians adjudicated KT results to determine if any detections were a probable cause. Difference in time from KT pathogen detection and infection onset was calculated.
UNASSIGNED: Of the 70 participants, mean age was 49.9 years. For CMV surveillance, positive percent agreement was 100% and negative percent agreement was 90%. There was strong correlation between CMV DNA and KT molecules per microliter (r 2: 0.84, P < .001). Of the 32 SMT+/KT+ infectious events, KT identified 26 earlier than SMT (median: -12 days) and an additional 5 diagnostically difficult pathogens identified by KT but not SMT.
UNASSIGNED: KT detected CMV with high accuracy and correlation with quantitative polymerase chain reaction. Among infectious events, KT demonstrated additive clinical utility by detecting pathogens earlier than SMT and those not detected by SMT.
摘要：
■这项研究描述了Karius检验（KT）的临床实用性和有效性，血浆微生物无细胞DNA测序平台，作为造血干细胞移植（HCT）接受者的感染监测工具，包括监测巨细胞病毒（CMV）和检测相对于标准微生物检测（SMT）的感染。
■预期，观察性队列研究在成人HCT受者(住院患者和门诊患者)中进行.在HCT前14天内从1个样本开始进行系列KT，然后从移植后7-63天每周一次，然后从HCT后3-12个月每月一次。KT与CMV聚合酶链反应的诊断性能以阳性百分比一致性和阴性百分比一致性进行评估。从病历中提取感染性事件（HCT后<12个月）。对于无SMT阳性的感染性事件，2名临床医生裁定KT结果，以确定是否有任何检测是可能的原因。计算KT病原体检测和感染发作的时间差。
■在70名参与者中，平均年龄为49.9岁.对于CMV监控，正百分比同意是100%，负百分比同意是90%。每微升CMVDNA和KT分子之间有很强的相关性(r2:0.84,P<.001)。在32例SMT+/KT+感染事件中，KT比SMT更早识别出26种（中位数：-12天），另外5种诊断困难的病原体由KT而不是SMT识别。
■KT以高精度检测CMV，并与定量聚合酶链反应相关。在传染病事件中，KT通过比SMT更早地检测病原体和SMT未检测到的病原体而证明了附加的临床实用性。
■预期，观察性队列研究在成人HCT受者(住院患者和门诊患者)中进行.在HCT前14天内从1个样本开始进行系列KT，然后从移植后7-63天每周一次，然后从HCT后3-12个月每月一次。KT与CMV聚合酶链反应的诊断性能以阳性百分比一致性和阴性百分比一致性进行评估。从病历中提取感染性事件（HCT后<12个月）。对于无SMT阳性的感染性事件，2名临床医生裁定KT结果，以确定是否有任何检测是可能的原因。计算KT病原体检测和感染发作的时间差。
■在70名参与者中，平均年龄为49.9岁.对于CMV监控，正百分比同意是100%，负百分比同意是90%。每微升CMVDNA和KT分子之间有很强的相关性(r2:0.84,P<.001)。在32例SMT+/KT+感染事件中，KT比SMT更早识别出26种（中位数：-12天），另外5种诊断困难的病原体由KT而不是SMT识别。
■KT以高精度检测CMV，并与定量聚合酶链反应相关。在传染病事件中，KT通过比SMT更早地检测病原体和SMT未检测到的病原体而证明了附加的临床实用性。
