Evidence map›Paper›PMID 40066816›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2025

Quantitative Microbial Cell-Free DNA Sequencing From Plasma: A Potential Biomarker for the Diagnosis of Staphylococcal Infection of Cardiac Implantable Electronic Devices.

Adolf W Karchmer, N Jenifer Kaufman, Sarah Y Park, Ronuk M Modi, Ahmed Abdul-Azim, Polly van den Berg, Jason D Matos, Daniel B Kramer, Peter J Zimetbaum

Abstract read
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. The evolving landscape ofFrontiers in immunology · 2026
    Pooled it
  2. Methicillin-resistant Staphylococcus aureus.Nature reviews. Disease primers · 2026
    Review
  3. Observational
  4. Metagenomic next-generation sequencing: new horizons in microbiology.Frontiers in cellular and infection microbiology · 2026
    Review
  5. Review
  6. ASM case reports · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Adolf W KarchmerDivision of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-5113-6395
N Jenifer KaufmanDivision of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0009-0009-0201-4266
Sarah Y ParkMedical Affairs, Karius, Inc, Redwood City, California, USA.
Ronuk M ModiDivision of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Ahmed Abdul-AzimDivision of Infectious Diseases, Department of Medicine, Robert Wood Johnson University Hospital, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.ORCID 0000-0001-7940-4320
Polly van den BergInfectious Diseases, Pennsylvania Hospital, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Jason D MatosDivision of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Daniel B KramerDivision of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0003-4241-3586
Peter J ZimetbaumDivision of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Funding

from Karius, Inc (to A. W. K.)
6 · The paper itself

Abstract

backgroundStaphylococcus aureus bacteremia in patients with cardiac implantable electronic devices (CIEDs) is often associated with infective endocarditis (CIED-IE). The CIED-IE diagnosis is syndromic. Diagnostic uncertainty is common. Frequently, these patients are classified as having possible CIED-IE, resulting in guideline-noncompliant treatment and heterogeneous outcomes. Improved outcomes require accurate diagnoses. In these patients, we evaluated whether metagenomic sequencing of microbial cell-free DNA (mcfDNA) in serial plasma specimens could improve diagnostic precision.

methodsWe studied 16 patients with staphylococcal bacteremia who were classified with definite or possible CIED-IE and recommended for device removal, if there was a positive blood culture within 7 days and no concurrent deep infection. Plasma specimens obtained at consent, before extraction, and during 96 hours after extraction underwent metagenomic sequencing and quantification of staphylococcal mcfDNA.

resultsIn 10 of 11 patients with definite CIED-IE, mcfDNA persisted during antibiotic therapy for prolonged durations (median, 11 days [interquartile range {IQR}, 7.5-15 days]). In these cases, mcfDNA concentration in plasma obtained early after lead extraction increased significantly and thereafter decreased rapidly. In 5 cases of possible CIED-IE, mcfDNA was undetectable after 6 days (IQR, 5.5-7.5 days) of antibiotic therapy and remained undetectable after CIED extraction. These mcfDNA patterns differ significantly (P = .001), suggesting 2 distinct patient populations: 1 with definite CIED-IE and 1 without lead infection.

conclusionsIf confirmed, these mcfDNA patterns can serve as biomarkers, together with clinical features, to improve precision in diagnosing or rejecting S. aureus CIED-IE. Strategically timed mcfDNA testing before and after CIED extraction may aid in planning therapy.

Indexed as

BacteremiaCell-Free Nucleic AcidsDefibrillators, ImplantableDNA, BacterialEndocarditis, BacterialPacemaker, ArtificialProsthesis-Related InfectionsStaphylococcal InfectionsStaphylococcus aureusAgedAged, 80 and overAnti-Bacterial AgentsBiomarkersFemaleHumansMaleAnti-Bacterial AgentsBiomarkersCell-Free Nucleic AcidsDNA, Bacterialcardiac implantable electronic devicesCIED infectioninfective endocarditisplasma microbial cell-free DNA

Identifiers

PMID40066816
PMCPMC12596351

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.