Use of Plasma Metagenomic Next-generation Sequencing for Pathogen Identification in Pediatric Endocarditis

Abstract

Pediatric infective endocarditis incurs significant morbidity and generally occurs among children with underlying heart disease. Identification of a pathogen is critical in determining appropriate therapy. However, standard diagnostic testing has limited sensitivity. We describe a case series of children with infective endocarditis in whom plasma next-generation sequencing (Karius, Redwood, CA) identified an organism in 8 of 10 cases.

Utility of Metagenomic Next-Generation Sequencing in Infective Endocarditis: A Systematic Review

“…The average turnaround time, which represents the time between sample collection to the time of availability of test results, was 3.2 days (SD 1.2 days) for mNGS versus 11 days for 16S PCR in a study [ 19 ], and 48 hours versus 1 week for culture method in another study [ 16 ].…”

“…Indeed, mNGS had an overall shortened turnaround time as compared to that for 16S rRNA PCR among studies included in the current systematic review. For example, the average turnaround time was 11 days for 16S rRNA PCR results from a reference laboratory compared to 3.2 days (SD 1.2 days) for mNGS results [ 19 ]. Similarly, most mNGS results were available within 48 hours in the study by Zeng and colleagues [ 16 ].…”

“…Because mNGS includes quantification in molecules per milliliter, this may be useful in both assessing the significance of an identified organism, and a response to antimicrobial therapy with a drop in quantification over time that would predict a corresponding decrease in microbiologic load and has been demonstrated by serial mNGS screening [ 19 ]. Additional investigations, however, are needed to further substantiate the utility of mNGS in predicting patient response to treatment.…”

“…Ultimately, the primary goal of mNGS is to ensure that appropriate antimicrobial therapy is being administered in patients with BCNE with the expectations that outcomes will be improved. To RK and colleagues, for example, reported that four of eight IE patients underwent revision of antimicrobial regimens, based on mNGS results, to enhance the likelihood of treatment success [ 19 ]. This was also the case in the study of Cai S et al, where antibiotic therapy was de-escalated to cephalosporin and aminoglycosides for six culture-negative IE subjects following pathogen identification by valve mNGS screening of valve tissue [ 15 ].…”

Native valve, prosthetic valve, and cardiac device-related infective endocarditis: A review and update on current innovative diagnostic and therapeutic strategies

“…To identify the causative pathogen in culture-negative patients not requiring valve surgery, To et al used cell-free plasma metagenomic next-generation sequencing (mNGS) to detect pathogens in cell-free plasma of pediatric IE patients ( To et al, 2021 ). Despite prolonged antibiotic treatment, the causative pathogen was successfully identified in eight out of the ten subjects.…”