Utility of Plasma Microbial Cell-Free DNA Decay Kinetics After Aortic Valve Replacement for Bartonella Endocarditis: Case Report

Abstract

BackgroundDetection and sequencing of circulating microbial cell-free DNA (mcfDNA) in plasma is an increasingly popular tool for diagnosing many infectious diseases, but could also be used to monitor the progress of infection. However, the decay of this microbial cell-free DNA in blood following treatment has not been previously characterized.Case PresentationA 53 year-old male was diagnosed with Bartonella quintana bioprosthetic aortic valve endocarditis by sequencing of the mcfDNA in the blood (Karius, Redwood City, CA). We then monitored the kinetics of decay of mcfDNA after parenteral antibiotics and valve resection in this individual. We measured plasma mcfDNA (Karius) in serial samples obtained in the operating room to calculate mcfDNA half-life after valve resection. After four weeks of parenteral antibiotics, Bartonella mcfDNA signal decreased by 78%. The signal subsequently rose during operative manipulation of the infected valve but dropped 81-fold over four hours following valve resection. The half-life of mcfDNA between the time shortly following resection of the infected valve and 24 to 48 hours post-operatively was between 35 and 115 minutes. The trend in mcfDNA signal was characterized by rapid and then slower phases of decay within 24 hours, and little change between 24 and 48 hours.ConclusionsThis study is one of the first to characterize decay kinetics of mcfDNA and highlights the potential of monitoring mcfDNA in addressing major challenges in infective endocarditis management, including monitoring the response to therapy, and as an early screen for recurrence.

Plasma Microbial Cell-free DNA Sequencing from Over 15,000 Patients Identified a Broad Spectrum of Pathogens

“…Constraints of the underlying data structure prevented analyzing the data from those patients who had repeated testing to determine whether these tests were performed serially to diagnose new suspected infections or to monitor therapy response or conduct pathogen surveillance among immunocompromised patients as suggested by others (8,26,(62)(63)(64). Further, the underlying data structure limited our ability to stratify the results by notable improvements to the bioinformatics pipeline over the course of the study period.…”

Plasma Microbial Cell-Free DNA Sequencing from over 15,000 Patients Identified a Broad Spectrum of Pathogens

“…In addition, infectious disease and hematology/oncology providers comprised most (78%) of the ordering clinicians, aligning with expectations that these clinicians commonly care for critically ill and IC patients with difficult-to-diagnose infections. Constraints of the underlying data structure prevented analyzing the data from the 12% of patients who had repeated testing to determine whether these tests were performed serially to diagnose new suspected infections or to monitor therapy response or conduct pathogen surveillance among immunocompromised patients as described by others ( 8 , 26 , 64 – 66 ). Further, the underlying data structure limited our ability to stratify the results by improvements to the bioinformatics pipeline over the course of the study period.…”

Exploring the Role of Circulating Cell-Free DNA in Disease Diagnosis and Therapy

“…The primary pathways of ccfDNA release are apoptosis (programmed cell death) and necrosis (cell death due to injury or disease), each characterized by distinct patterns of DNA fragmentation. In apoptosis, DNA is systematically fragmented into distinct sizes, typically around 180-200 base pairs, correlating with nucleosomal units, a pattern indicative of an orderly cellular disassembly process [41]. Conversely, necrosis results in the release of larger and more random DNA fragments due to the chaotic and uncontrolled breakdown of cells.…”