How is NGS changing the paradigm of infectious disease diagnosis?

Decisions on the choice of the right empiric therapy have been challenging owing to the growing burden of antibiotic resistance and the inherent limitations of current-day diagnostics. Blanket empiric therapy with broad-spectrum antimicrobials adds to the cost, toxic side-effects and selection pressure of de novo resistant microbes. Early detection and identification of bloodstream pathogens along with resistance patterns will improve population-level outcomes.

The existing gold standard of microbiological diagnosis is hindered by inefficient turnaround time, poor sensitivity (10-30%) and failure to detect fastidious and non-culturable organisms (1). Molecular diagnostic tests based on PCR technologies are hypothesis-driven, with a high dependence on the primer selection. This allows identification of only a limited range of pathogens; thus failing to detect unknown pathogens which can lead to ambiguous results and confound clinical decision making (2).

Through NGS technologies currently may not replace traditional microbiological diagnostics, it definitely is changing the face of it (3), with the scope of unbiased and data-driven detection of multiple classes of organisms on a single platform. The development of real-time sequencing platforms such as Oxford Nanopore sequencing has scaled resolution, accuracy, and shorter turnaround time compared to currently available commercial techniques. Routine implementation of NGS in the clinical setting will markedly improve point-of-care pathogen detection (4).Accurate, comprehensive and rapid diagnostics (5,6) can thus aid initiation of optimal therapy, better patient outcomes and shorter hospital stay. A comprehensive and scalable diagnostic technology with improved sensitivity and specificity for pathogen detection is essential to monitor the extent of the problem, develop feasible local diagnostic algorithms and databases that might aid in clinical decision making, limit the emergence of resistant pathogens and alleviate the fatality rate.

REFERENCES :

1. Cao XG, Zhou SS, Wang CY, Jin K, Meng HD. The diagnostic value of next-generation sequencing technology in sepsis. Front Cell Infect Microbiol. 2022 Sep 14;12:899508.
2. Grumaz C, Hoffmann A, Vainshtein Y, Kopp M, Grumaz S, Stevens P, et al. Rapid Next-Generation Sequencing-Based Diagnostics of Bacteremia in Septic Patients. J Mol Diagn [Internet]. 2020 Mar 1 [cited 2023 Dec 4];22(3):405–18.Available from: https://pubmed.ncbi.nlm.nih.gov/32146977/
3. Betz BL, Mroz P, Billington C, Hilt EE, Ferrieri P. Next Generation and Other Sequencing Technologies in Diagnostic Microbiology and Infectious Diseases. Genes 2022, Vol 13, Page 1566 [Internet]. 2022 Aug 31 [cited 2023 Dec 12];13(9):1566. Available from: https://www.mdpi.com/2073-4425/13/9/1566/htm
4. Li JY, Shen GG, Liu TG, Tang L V, Xia LH, Hu Y. Nanopore-targeted sequencing for simultaneous diagnosis of suspected sepsis and early targeted therapy. Ann Transl Med [Internet]. 2021 [cited 2023 Dec 12];9(23):1749. Available from: https://dx.doi.org/10.21037/atm-21-2923
5. Liu J, Zhang Q, Dong YQ, Yin J, Qiu YQ. Diagnostic accuracy of metagenomic next-generation sequencing in diagnosing infectious diseases: a meta-analysis. Scientific Reports 2022 12:1 [Internet]. 2022 Dec 5 [cited 2023 Dec 12];12(1):1–10.Available from: https://www.nature.com/articles/s41598-022-25314-y
6. Hong M, Peng D, Fu A, Wang X, Zheng Y, Xia L, et al. The application of nanopore targeted sequencing in the diagnosis and antimicrobial treatment guidance of bloodstream infection of febrile neutropenia patients with
7. hematologic disease. J Cell Mol Med [Internet]. 2023 Feb 1 [cited 2023 Dec 12];27(4):506–14. Available from:https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.17651