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Reviews of "A New Method Using Rapid Nanopore Metagenomic Cell-free DNA Sequencing to Diagnose Bloodstream Infections: A Prospective Observational Study"

F Santoro(Università degli Studi di Siena)&D Pinzauti(The Bioarte ltd.)|📗📗📗📗◻️•N Urosevir(University of Western Australia)|📗📗📗📗◻️•Y Joo Lee(Memorial Sloan Hospital)|📒📒📒◻️◻️•Z Weiss&S Harford(Tufts)|📗📗📗📗◻️•B Lutz&Q Wang&R Britton(University of Washington)|📗📗📗📗◻️

Published onJun 13, 2024
Reviews of "A New Method Using Rapid Nanopore Metagenomic Cell-free DNA Sequencing to Diagnose Bloodstream Infections: A Prospective Observational Study"
key-enterThis Pub is a Review of
A new method using rapid Nanopore metagenomic cell-free DNA sequencing to diagnose bloodstream infections: a prospective observational study
A new method using rapid Nanopore metagenomic cell-free DNA sequencing to diagnose bloodstream infections: a prospective observational study
Description

Abstract Background Bloodstream infections (BSIs) remain a major cause of mortality, in part due to many patients developing sepsis or septic shock. To survive sepsis, it is paramount that effective antimicrobial therapy is initiated rapidly to avoid excess mortality, but the current gold-standard to identify the pathogen in BSIs, blood culturing, has great limitations with a long turnaround time and a poor sensitivity. This delay to correct empiric broad-spectrum antimicrobial treatments leads to excess mortality and antimicrobial resistance development.Methods In this study we developed a metagenomic next-generation sequencing (mNGS) assay utilizing the Oxford Nanopore Technologies platform to sequence microbial cell-free DNA from blood plasma. The method was evaluated in a prospective observational clinical study (n=40) in an emergency ward setting, where a study sample was taken from the same venipuncture as a blood culture sample from patients with a suspected BSI.Findings Nanopore mNGS confirmed all findings in patients with a positive blood culture (n=11), and identified pathogens relevant to the acute infection in an additional 11 patients with a negative blood culture. In an analysis of potential impact on the antibiotic treatment, we found that 59% (n=13) of mNGS positive answers could have impacted the treatment, with five cases of a change from ineffective to effective therapy.Interpretation This study demonstrates that culture-independent Nanopore mNGS directly on blood plasma could be a feasible alternative to blood culturing for infection diagnostics for patients admitted with a severe infection or sepsis. The method identified a relevant pathogen in patients with a broad range of etiologies including urinary tract infections and lower respiratory tract infections. With a turnaround time of 6 hours the method could provide unprecedented speed and sensitivity in BSI diagnostics.

To read the original manuscript, click the link above.

Summary of Reviews: The researchers of this prospective study developed a novel Nanopore DNA sequencing method (mNGS assay) to detect bloodstream infections and identify relevant pathogens. The study showed that the assay could potentially revolutionize antibiotic therapy for septic patients with faster turnaround times and greater sensitivity than traditional blood cultures. Reviewers agree that the methodology is well-designed and the evidence is reliable. However, they suggest including more technical details and caution against overestimating the method's capabilities while emphasizing its supplementary role alongside blood cultures. Despite these limitations, the findings are interesting enough to warrant further validation studies to assess the mNGS assay's application in clinical settings.   

Reviewer 1 (Francesco S… & David P…) | 📗📗📗📗◻️

Reviewer 2 (Nadia U…) | 📗📗📗📗◻️

Reviewer 3 (Yeon J…) | 📒📒📒 ◻️◻️

Reviewer 4 (Zoe W… & Sean H…) | 📗📗📗📗◻️

Reviewer 5 (Barry L… & Qin W… & Rhett B…) | 📗📗📗📗◻️

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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