Greninger Alexander L, Naccache Samia N
Department of Laboratory Medicine, University of Washington, Seattle, WA;
Department of Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA.
J Appl Lab Med. 2019 Jan;3(4):643-653. doi: 10.1373/jalm.2018.026120. Epub 2018 Nov 30.
Metagenomic next-generation sequencing (mNGS) has emerged as a promising technology that enables pan-pathogen detection from any source. However, clinical utility and practical integration into the clinical microbiology work flow and a bloodstream infection detection algorithm are currently uncharted. In the context of bloodstream infections, the challenges associated with blood culture, including sensitivity, postantibiotic treatment, attaining sufficient volumes sufficient volumes, and turnaround time, are well-known. Molecular assays have helped expedite turnaround time, especially when performed directly from positive culture media bottles. mNGS offers an unbiased but more complex version of molecular testing directly from sample, but it is unclear how and if it should be implemented in the clinical microbiology laboratory today.
Here we map out the potential utility and application of mNGS tests to infectious disease diagnostics from blood sources, including intrinsic limitations of the methodology in diagnosing bloodstream infections and sepsis vs DNAemia, current barriers to integration into routine workup, and milestones that may need to be met before implementation.
Polymerases and pores move faster than bugs divide, so the thermodynamics of mNGS adoption for bloodstream infection is favorable. Nonetheless, considerable activation barriers exist that will slow this likely diagnostic transition. We eagerly await the manufacturer who designs an integrated sample-to-answer box to do for mNGS what has been done for other aspects of molecular detection.
宏基因组下一代测序(mNGS)已成为一项有前景的技术,能够从任何来源进行泛病原体检测。然而,其临床实用性以及实际融入临床微生物学工作流程和血流感染检测算法目前尚不清楚。在血流感染的背景下,与血培养相关的挑战,包括敏感性、抗生素治疗后情况、获取足够的血量以及周转时间等,都是众所周知的。分子检测有助于加快周转时间,特别是直接从阳性培养基瓶中进行检测时。mNGS提供了一种直接从样本进行的无偏倚但更复杂的分子检测方式,但目前尚不清楚它应如何以及是否应在临床微生物学实验室中实施。
在此,我们阐述了mNGS检测在血液来源传染病诊断中的潜在用途和应用,包括该方法在诊断血流感染和脓毒症与菌血症方面的内在局限性、当前融入常规检查的障碍以及实施前可能需要达到的里程碑。
聚合酶和孔的移动速度比细菌分裂速度快,因此mNGS用于血流感染的热力学条件是有利的。尽管如此,仍存在相当大的激活障碍,这将减缓这一可能的诊断转变。我们热切期待有制造商设计出一个集成的样本到答案盒,为mNGS实现其他分子检测方面已取得的成果。