#2: Use of Plasma Metagenomic Next Generation Sequencing for Pathogen Identification in Pediatric Endocarditis

Abstract

\n \n \n Pediatric infective endocarditis (IE) incurs significant morbidity and most commonly occurs among children with underlying heart disease. Identification of causative pathogens on blood culture allows for more targeted antibiotic therapy, optimizing patient outcomes. However, standard diagnostic testing has limited sensitivity. As a result, there is an opportunity to explore alternative methods to identify pathogens in IE using cell-free plasma next generation sequencing (mNGS). mNGS utilizes a high-throughput approach that is culture-independent and non-invasive to detect microbial DNA. We describe a single center retrospective case series of children with IE in whom plasma mNGS was sent as part of the diagnostic evaluation.\n \n \n \n In this case series, we evaluated the impact of mNGS on the clinical management of IE by conducting a retrospective chart review of children hospitalized with IE from January 1, 2017 to January 17, 2020. Inclusion criteria included subjects 0–21 years of age who had a diagnosis of IE based on admission diagnosis and problem list. Demographics, echocardiography and diagnostics were obtained by chart review.\n \n \n \n We identified 14 children who were diagnosed with IE, 10 of whom had mNGS sent for diagnostic testing. mNGS detected an organism in 8 of 10 (80%) children as compared to standard of care blood cultures and 16S PCR which identified an organism in only 5 of 10 (30%). Out of 8 subjects with organisms identified by mNGS, clinical management was impacted in 4 of 8 subjects and 3 subjects were only diagnosed through mNGS.\n \n \n \n Although blood and tissue cultures are the historical gold standard for organism identification in IE, new diagnostic modalities such as mNGS may be more sensitive. This could lead to more targeted and possibly more effective therapeutic regimens in cases when empiric antibiotic therapy may hinder pathogen identification. In at least one instance, a change in antibiotic choice to penicillin to target Corynebacterium diphtheriae resulted in a clinical cure that may not have otherwise been achieved. As a result of mNGS, three other subjects also had changes in management that resulted in narrowing of antibiotic choice or adjustments to the antibiotic regimen. Our observations suggest that mNGS is more sensitive than standard blood cultures and that the clinical utility of mNGS may be beneficial to the management of infective endocarditis in children.\n