4.5 Review

Rapid metagenomics for diagnosis of bloodstream and respiratory tract nosocomial infections: current status and future prospects

Journal

EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
Volume 21, Issue 4, Pages 371-380

Publisher

TAYLOR & FRANCIS AS
DOI: 10.1080/14737159.2021.1906652

Keywords

Antimicrobial resistance (AMR); blood stream infection; clinical metagenomics (CMg); diagnosis; Infection; mNGS; respiratory tract infection; sepsis; sequencing

Categories

Funding

  1. MRC Doctoral Antimicrobial Research Training (DART) Industrial CASE Programme
  2. Innovative UK grant [TS/S00887X/1]
  3. Biotechnology and Biological Sciences Research Council (BBSRC))
  4. BBSRC Institute Strategic Programme Microbes in the Food Chain [BB/R012504/1, BBS/E/F/000PR10348, BBS/E/F/000PR10349, BBS/E/F/000PR10351]

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Clinical metagenomics (CMg) offers a potential alternative to slow and insensitive microbiological culture for the diagnosis of nosocomial infections, particularly in distinguishing between BSI and LRTI. CMg approaches are more accurate in diagnosing LRTI due to higher pathogen numbers, while challenges remain for accurately diagnosing BSI. Advances in CMg for LRTI are likely to be implemented in hospitals within the next 2-5 years.
Introduction: Nosocomial infections represent a major problem for the health-care systems worldwide. Currently, diagnosis relies on microbiological culture, which is slow and has poor sensitivity. While waiting for a diagnosis, patients are treated with empiric broad spectrum antimicrobials, which are often inappropriate for the infecting pathogen. This results in poor patient outcomes, poor antimicrobial stewardship and increased costs for health-care systems. Areas covered: Clinical metagenomics (CMg), the application of metagenomic sequencing for the diagnosis of infection, has the potential to become a viable alternative to culture that can offer rapid results with high accuracy. In this article, we review current CMg methods for the diagnosis of nosocomial bloodstream (BSI) and lower respiratory-tract infections (LRTI). Expert opinion: CMg approaches are more accurate in LRTI compared to BSI. This is because BSIs are caused by low pathogen numbers in a high background of human cells. To overcome this, most approaches focus on cell-free DNA, but, to date, these tests are not accurate enough yet to replace blood culture. The higher pathogen numbers in LRTI samples make this a more suitable for CMg and accurate approaches have been developed, which are likely to be implemented in hospitals within the next 2-5 years.

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