Plasma Metagenomic Next-Generation Sequencing Assay for Identifying Pathogens: a Retrospective Review of Test Utilization in a Large Children's Hospital

Niles, Denver T.; Wijetunge, Dona Saumya S.; Palazzi, Debra L.; Singh, Ila R.; Revell, Paula A.

doi:10.1128/jcm.00794-20

Cited by 42 publications

(37 citation statements)

References 15 publications

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“…However, while a positive identification by mNGS can be helpful to clinicians, a negative result does not necessarily rule out infection as mNGS has missed important pathogens identified by conventional testing. 13 In our study, mNGS identified a plausible cause of infection, defined as a definite, probable or possible infection, in 49.7% of patients tested. This is comparable with a pediatric review that found 56% of mNGS results to be clinically relevant 10 but is lower than a recent prospective study that found a plausible cause of infection in 85.4% of patients with febrile neutropenia.…”

Section: Discussionmentioning

confidence: 55%

Clinical Impact of Plasma Metagenomic Next-generation Sequencing in a Large Pediatric Cohort

Niles

Revell

Ruderfer

et al. 2021

Pediatric Infectious Disease Journal

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Background: Plasma metagenomic next-generation sequencing (mNGS) has the potential to detect thousands of different organisms with a single test. There are limited data on the real-world impact of mNGS and even less guidance on the types of patients and clinical scenarios in which mNGS testing is beneficial. Methods: A retrospective review of patients who had mNGS testing as part of routine clinical care at Texas Children's Hospital from June 2018-August 2019 was performed. Medical records were reviewed for pertinent data. An expert panel of infectious disease physicians adjudicated each unique organism identified by mNGS for clinical impact. Results: There were 169 patients with at least one mNGS test. mNGS identified a definitive, probable or possible infection in 49.7% of patients. mNGS led to no clinical impact in 139 patients (82.2%), a positive impact in 21 patients (12.4%), and a negative impact in 9 patients (5.3%). mNGS identified a plausible cause for infection more often in immunocompromised patients than in immunocompetent patients (55.8% vs. 30.0%, P = 0.006). Positive clinical impact was highest in patients with multiple indications for testing (37.5%, P = 0.006) with deep-seated infections, overall, being most often associated with a positive impact. Conclusion: mNGS testing has a limited real-world clinical impact when ordered indiscriminately. Immunocompromised patients with well-defined deep-seated infections are likely to benefit most from testing. Further studies are needed to evaluate the full spectrum of clinical scenarios for which mNGS testing is impactful.

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Section: Discussionmentioning

confidence: 55%

Clinical Impact of Plasma Metagenomic Next-generation Sequencing in a Large Pediatric Cohort

Niles

Revell

Ruderfer

et al. 2021

Pediatric Infectious Disease Journal

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“…These viruses have poorly understood clinical signi cance. The limited clinical impact of plasma mNGS has also been reported in patients with infectious diseases [15,41]. Armstrong et al also showed that the cfDNA NGS could identify fungal pathogens and had the potential to limit excessive empiric antifungal use [42].…”

Section: Discussionmentioning

confidence: 99%

A Paired Comparison of Plasma and Bronchoalveolar Lavage Fluid for Metagenomic Next-Generation Sequencing in Critically Ill Patients with Suspected Severe Pneumonia

Sun

Liu

et al. 2022

Preprint

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Background: Plasma cell-free DNA (cfDNA) metagenomic next-generation sequencing (mNGS) has emerged as an attractive and less invasive technique for pathogen detection. However, only few studies have demonstrated the need for simultaneous plasma and bronchoalveolar lavage fluid (BALF) mNGS in patients with severe pneumonia.Methods: This study retrospectively performed a paired comparison of BALF and plasma mNGS in critically ill patients with suspected severe pneumonia from April 2019 to December 2020, who were divided into mNGS results match and mismatch groups. The diagnostic performance was compared between BALF and plasma mNGS, using the clinical composite diagnosis as the reference standard. The impact of mNGS results was also assessed.Results: In total, 57 patients were included in this study and divided into the plasma mNGS match with BALF group (n=15) and mismatch group (n=40). There were no significant differences in baseline characteristics and total 28-day mortality between the match and mismatch groups. Fifty-three patients were diagnosed with microbiologically confirmed severe pneumonia, with 49% having polymicrobial infections. There were significant differences in the BALF sensitivity and plasma mNGS (100% vs. 42%, P < 0.001), and the diagnostic accuracy was 96% and 46%, respectively. There were no significant differences in the baseline characteristics and total 28-day mortality between the mNGS match and mismatch groups. However, in the mismatch group, more bacterial infections were detected in BALF mNGS than in plasma mNGS (47.5% vs. 23.1%, P = 0.040). Additionally, though plasma mNGS detected additional microorganisms in 11/53 patients, a beneficial impact was obtained only in 5 out of 11 patients.Conclusions: This study does not support the simultaneous mNGS of BALF and plasma samples. Prospective studies are required to clarify the optimal indications for cfDNA mNGS as an additional test for pneumonia.

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“…However, a positive plasma mNGS result for MTB complex would significantly alter a patient's management before SCT and potentially increase the chance of a good outcome post-transplant. [23][24][25] Additionally, while plasma mNGS is costly and in some cases may not add additional diagnostic information compared to conventional testing, 17 in immunocompromised patients requiring SCT, whose conventional, immune-based testing for mycobacterial infections are unavailable or unreliable, and who are receiving or have recently received broad-spectrum antimicrobial therapy or prophylaxis (impacting culture results), plasma mNGS could offer an alternative, non-invasive, rapid screening tool for infectious pathogens. Future studies should consider assessing the specificity and sensitivity of plasma mNGS in screening BCG-vaccinated immunocompromised infants for disseminated BCG infection before SCT.…”

Section: Discussionmentioning

confidence: 99%

Plasma Metagenomic Sequencing Expedites Diagnosis of Disseminated BCG in an Infant With IKBKB Mutation

Taylor

Nicholas

Satter

et al. 2022

Pediatric Infectious Disease Journal

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Background: Infants with inborn errors of immunity (IEI), born in countries where Bacillus-Calmette-Guerin (BCG) vaccination is recommended at birth, are at risk of developing infectious complications following vaccination. A prompt diagnosis of disseminated BCG infection in these infants is essential, as many will require stem cell transplantation (SCT) for the immunologic cure. In patients with IEI, the mortality risk from disseminated mycobacterial infection is high, both before and following SCT. Methods: A 7-month-old Qatari infant with an IEI, homozygous IKBKB gene mutation, was evaluated at our institution for SCT. He had a history of recurrent pneumonias, but pretransplant evaluation revealed negative cultures from bronchoalveolar fluid, blood and urine. At 8 months of age, the infant developed skin nodules of unclear etiology, prompting additional evaluation. Results: Given his profound immunosuppression and receipt of broadspectrum antimicrobials, plasma metagenomic next-generation sequencing (mNGS) was obtained and identified Mycobacterium tuberculosis complex within 72 hours. A skin biopsy was performed, and antimycobacterial therapy was initiated. Mycobacterium bovis-BCG was confirmed from cultures 3 weeks later. Treatment was complicated by elevated serum liver transaminases and aminoglycoside-associated high-frequency hearing loss. The infant completed 14 months of treatment from engraftment. Evaluation for active BCG infection after SCT was negative. Conclusion:In an infant with a unique IEI, plasma mNGS provided the first diagnosis of disseminated BCG infection. We believe that early initiation of antimycobacterial treatment improved the infant's clinical outcome. Plasma mNGS testing should be considered as a noninvasive screen for infectious pathogens in children with IEIs before SCT.

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Plasma Metagenomic Next-Generation Sequencing Assay for Identifying Pathogens: a Retrospective Review of Test Utilization in a Large Children's Hospital

Cited by 42 publications

References 15 publications

Clinical Impact of Plasma Metagenomic Next-generation Sequencing in a Large Pediatric Cohort

Clinical Impact of Plasma Metagenomic Next-generation Sequencing in a Large Pediatric Cohort

A Paired Comparison of Plasma and Bronchoalveolar Lavage Fluid for Metagenomic Next-Generation Sequencing in Critically Ill Patients with Suspected Severe Pneumonia

Plasma Metagenomic Sequencing Expedites Diagnosis of Disseminated BCG in an Infant With IKBKB Mutation

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