428 - Use of plasma next-generation sequencing for the diagnosis of pediatric infectious diseases in the inpatient setting: a single-center experience

Monday, May 1, 2023

9:30 AM – 11:30 AM ET

Poster Number: 428
Publication Number: 428.418

Julianne V. Green, University of Louisville, Louisville, KY, United States; Julianne V. Green, University of Louisville, Louisville, KY, United States

Presenting Author(s)

Julianne V. Green, MD, PhD (she/her/hers)

Associate Professor
University of Louisville
University of Louisville
Louisville, Kentucky, United States

Background: The diagnosis of infectious disease is often fraught with complications. Cultures may lack sensitivity due to low collection volume, pretreatment, or inability to grow pathogenic organisms. The suspected site of infection may be inaccessible for sampling. PCR technology is highly specific but available for a relatively small subset of organisms.

Objective: To explore the utility of metagenomic next-generation sequencing (mNGS) of microbial cell-free DNA (mcf DNA) in plasma as a culture-independent method for the diagnosis of pediatric infectious diseases.

Design/Methods:

Retrospective chart review of a two-year time period from July 2020 to July 2022. Plasma samples were analyzed for infectious pathogens using mNGS at a CLIA-certified laboratory (Karius, Redwood City, CA) which identifies over 1400 pathogens. Involvement of pediatric infectious diseases was required.

Results:

Karius tests were sent for 38 pediatric patients representing 42 unique clinical scenarios. Two thirds of patients were critically ill in the pediatric ICU. Children with congenital heart disease (40%) and those with no past medical history (30%) made up the majority of patients; the rest were oncologic, immunocompromised, or children with chronic illnesses. Concern for a focal infection (cardiac, lung, central line, musculoskeletal etc.) predominated. Results for 78% of samples were finalized within 24 hours of receipt.

Testing was positive in 24 patients. Most (82%) returned a single organism which confirmed an infectious disease diagnosis. The Karius test exhibited 100% sensitivity in four patients with RV to PA conduits with endocarditis, including a rapid diagnosis of Coxiella burnetii. No organisms were detected in the plasma of 13 patients; these negative results were used to rule out infection in over half (62%) of patients with no subsequent adverse events. Overall, Karius test results (whether organisms found or not) significantly improved antibiotic usage (de-escalation/cessation) in over half (52%) of patients. In one patient, the Karius test failed to diagnose an infection (histoplasmosis) that was diagnosed by conventional means (urine antigen).

Conclusion(s): Metagenomic next-generation sequencing of microbial cell-free DNA in plasma was found to be a useful adjunctive method for the diagnosis of pediatric infectious diseases in the inpatient setting, especially in the diagnosis of culture negative endocarditis. Test results significantly improved antimicrobial stewardship decision-making in over half of patients tested. Further studies are warranted to expand understanding of the technique’s utility.