Graf Erin H, Bryan Andrew, Bowers Michael, Grys Thomas E
Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ, United States.
J Appl Lab Med. 2025 Jan 3;10(1):171-183. doi: 10.1093/jalm/jfae122.
Metagenomic sequencing of plasma has been advertised by Karius, Inc. as a way to diagnose a variety of infectious syndromes. Due to the lack of robust evidence of clinical utility, our laboratory began actively stewarding Karius testing. Microbiology Directors recommended cancelation of Karius orders when certain criteria were identified. We set out to review Karius test requests in a 52-month period of stewardship, during which we recommended cancellation on 21 of 57 orders (37%). Of Karius tests sent on samples with negative conventional testing, only 3 (7%) had positive results for Karius with plausible explanatory etiologies. Of these three cases, two were empirically covered for the positive finding without improvement and one case was never treated. Twelve (29%) had positive results that were noted by infectious diseases (ID) to reflect insignificant detections. Given the 4-fold higher detection of insignificant Karius results, we set out to systematically analyze the literature for the experience of insignificant detections at other centers. When we compared studies that included healthy controls or had clinical adjudication of positive Karius findings by ID physicians, we found a median of 17.5% of individual patients that had positive insignificant detections of potential pathogenic bacteria or fungi. The most frequently detected species were as likely to be clinically adjudicated to be insignificant as they were to be significant within the same studies. Overall, these findings highlight limited utility of Karius testing and a need for careful stewardship, not only to ensure it is sent on patients who may benefit, but also to ensure results of potential pathogens are interpreted cautiously.
Karius公司宣传血浆宏基因组测序是诊断多种感染综合征的一种方法。由于缺乏临床实用性的有力证据，我们实验室开始积极管理Karius检测。微生物学主任建议在确定某些标准时取消Karius检测订单。我们着手回顾在52个月的管理期内的Karius检测请求，在此期间，我们建议取消57份订单中的21份（37%）。在常规检测为阴性的样本上进行的Karius检测中，只有3份（7%）的Karius检测结果为阳性，且病因解释合理。在这三个病例中，有两个病例针对阳性结果进行了经验性治疗，但病情没有改善，还有一个病例从未接受治疗。有12份（29%）检测结果呈阳性，传染病科（ID）指出这些结果反映的是无意义的检测结果。鉴于Karius无意义结果的检测率高出4倍，我们着手系统分析文献，了解其他中心无意义检测的情况。当我们比较纳入了健康对照或由ID医生对Karius阳性结果进行临床判定的研究时，我们发现，在个体患者中，有潜在致病细菌或真菌的无意义阳性检测结果的中位数为17.5%。在同一研究中，最常检测到的物种在临床判定中无意义的可能性与有意义的可能性一样大。总体而言，这些发现凸显了Karius检测的实用性有限，以及需要谨慎管理，不仅要确保将其用于可能受益的患者，还要确保对潜在病原体的检测结果进行谨慎解读。
