Williams Austin, Webster William Zach, Cai Chao, Milgrom Alexander, Al-Hasan Majdi, Bookstaver P Brandon
Department of Pharmacy, Prisma Health Midlands, Columbia, SC, USA.
Division of Infectious Diseases, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
Ther Adv Infect Dis. 2024 Feb 23;11:20499361241232854. doi: 10.1177/20499361241232854. eCollection 2024 Jan-Dec.
Metagenomic next-generation sequencing (mNGS) testing identifies thousands of potential pathogens in a single blood test, though data on its real-world diagnostic utility are lacking.
Determine the diagnostic utility of mNGS testing in practice and factors associated with high clinical utility.
Retrospective cohort study of mNGS tests ordered from June 2018 through May 2020 at a community teaching hospital.
Tests were included if ordered for diagnostic purposes in patients with probable or high clinical suspicion of infection. Exclusions included patient expiration, hospice care, or transfer outside of the institution. Utility criteria were established a priori by the research team. Two investigators independently reviewed each test and categorized it to either high or low diagnostic utility. Reviewer discordance was referred to a third investigator. The stepwise multiple regression method was used to identify clinical factors associated with high diagnostic utility.
Among 96 individual tests from 82 unique patients, 80 tests met the inclusion criteria for analysis. At least one potential pathogen was identified in 58% of tests. Among 112 pathogens identified, there were 74 bacteria, 25 viruses, 12 fungi, and 1 protozoon. In all, 46 tests (57.5%) were determined to be of high diagnostic utility. Positive mNGS tests were identified in 36 (78.3%) and 11 (32.4%) of high and low diagnostic utility tests, respectively ( < 0.001). Antimicrobials were changed after receiving test results in 31 (67.4%) of high utility tests and 4 (11.8%) of low utility tests ( < 0.0001). In the multiple regression model, a positive test [odds ratio (OR) = 10.9; 95% confidence interval (CI), 3.2-44.4] and consultation with the company medical director (OR = 3.6; 95% CI, 1.1-13.7) remained significantly associated with high diagnostic utility.
mNGS testing resulted in high clinical utility in most cases. Positive mNGS tests were associated with high diagnostic utility. Consultation with the Karius medical director is recommended to maximize utility.
宏基因组下一代测序（mNGS）检测可在单次血液检测中识别数千种潜在病原体，但缺乏其在实际应用中诊断效用的数据。
确定mNGS检测在实际应用中的诊断效用以及与高临床效用相关的因素。
对2018年6月至2020年5月在一家社区教学医院进行的mNGS检测进行回顾性队列研究。
如果对疑似或高度怀疑感染的患者出于诊断目的进行检测，则纳入研究。排除标准包括患者死亡、临终关怀或转至机构外。效用标准由研究团队预先确定。两名研究人员独立审查每项检测，并将其分类为高诊断效用或低诊断效用。审查员之间的不一致由第三名研究人员裁决。采用逐步多元回归方法确定与高诊断效用相关的临床因素。
在来自82名独特患者的96项个体检测中，80项检测符合分析纳入标准。58%的检测中至少鉴定出一种潜在病原体。在鉴定出的112种病原体中，有74种细菌、25种病毒、12种真菌和1种原生动物。总体而言，46项检测（57.5%）被确定为具有高诊断效用。高诊断效用检测和低诊断效用检测中分别有36项（78.3%）和11项（32.4%）的mNGS检测呈阳性（P<0.001）。在收到检测结果后，高效用检测中有31项（67.4%）和低效用检测中有4项（11.8%）的抗菌药物发生了改变（P<0.0001）。在多元回归模型中，检测呈阳性[比值比（OR）=10.9；95%置信区间（CI），3.2-44.4]以及与公司医学主任会诊（OR=3.6；95%CI，1.1-13.7）仍与高诊断效用显著相关。
mNGS检测在大多数情况下具有较高的临床效用。mNGS检测呈阳性与高诊断效用相关。建议与卡里乌斯医学主任会诊以最大化效用。
