Durham Veterans Affairs Health Care System, Durham, NC.
Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC.
Crit Care Med. 2021 Oct 1;49(10):1651-1663. doi: 10.1097/CCM.0000000000005085.
Host gene expression signatures discriminate bacterial and viral infection but have not been translated to a clinical test platform. This study enrolled an independent cohort of patients to describe and validate a first-in-class host response bacterial/viral test.
Subjects were recruited from 2006 to 2016. Enrollment blood samples were collected in an RNA preservative and banked for later testing. The reference standard was an expert panel clinical adjudication, which was blinded to gene expression and procalcitonin results.
Four U.S. emergency departments.
Six-hundred twenty-three subjects with acute respiratory illness or suspected sepsis.
Forty-five-transcript signature measured on the BioFire FilmArray System (BioFire Diagnostics, Salt Lake City, UT) in ~45 minutes.
Host response bacterial/viral test performance characteristics were evaluated in 623 participants (mean age 46 yr; 45% male) with bacterial infection, viral infection, coinfection, or noninfectious illness. Performance of the host response bacterial/viral test was compared with procalcitonin. The test provided independent probabilities of bacterial and viral infection in ~45 minutes. In the 213-subject training cohort, the host response bacterial/viral test had an area under the curve for bacterial infection of 0.90 (95% CI, 0.84-0.94) and 0.92 (95% CI, 0.87-0.95) for viral infection. Independent validation in 209 subjects revealed similar performance with an area under the curve of 0.85 (95% CI, 0.78-0.90) for bacterial infection and 0.91 (95% CI, 0.85-0.94) for viral infection. The test had 80.1% (95% CI, 73.7-85.4%) average weighted accuracy for bacterial infection and 86.8% (95% CI, 81.8-90.8%) for viral infection in this validation cohort. This was significantly better than 68.7% (95% CI, 62.4-75.4%) observed for procalcitonin (p < 0.001). An additional cohort of 201 subjects with indeterminate phenotypes (coinfection or microbiology-negative infections) revealed similar performance.
The host response bacterial/viral measured using the BioFire System rapidly and accurately discriminated bacterial and viral infection better than procalcitonin, which can help support more appropriate antibiotic use.
宿主基因表达谱可区分细菌和病毒感染，但尚未转化为临床检测平台。本研究招募了一个独立的患者队列，以描述和验证一种首创的宿主反应细菌/病毒检测。
研究对象于 2006 年至 2016 年招募。采集入组血样并置于 RNA 保存液中，以备后续检测。参考标准是专家小组的临床判断，该判断对基因表达和降钙素原结果是盲法的。
美国 4 个急诊部。
623 例急性呼吸道疾病或疑似败血症患者。
在 BioFire FilmArray 系统（BioFire Diagnostics，盐湖城，犹他州）上测量 45 个转录本标志物，耗时约 45 分钟。
在 623 名细菌感染、病毒感染、混合感染或非传染性疾病患者中评估了宿主反应细菌/病毒检测的性能特征。将宿主反应细菌/病毒检测与降钙素原进行了比较。该检测可在约 45 分钟内提供细菌和病毒感染的独立概率。在 213 例患者的训练队列中，宿主反应细菌/病毒检测对细菌感染的曲线下面积为 0.90（95%置信区间，0.84-0.94），对病毒感染的曲线下面积为 0.92（95%置信区间，0.87-0.95）。在 209 例独立验证中，对细菌感染的曲线下面积为 0.85（95%置信区间，0.78-0.90），对病毒感染的曲线下面积为 0.91（95%置信区间，0.85-0.94），表现出类似的性能。在该验证队列中，该检测对细菌感染的平均加权准确率为 80.1%（95%置信区间，73.7%-85.4%），对病毒感染的准确率为 86.8%（95%置信区间，81.8%-90.8%）。这显著优于降钙素原观察到的 68.7%（95%置信区间，62.4%-75.4%）（p < 0.001）。在另外 201 例具有不确定表型（混合感染或微生物阴性感染）的患者队列中也显示出类似的性能。
使用 BioFire 系统测量的宿主反应细菌/病毒能更快更准确地区分细菌和病毒感染，优于降钙素原，有助于支持更合理的抗生素使用。
