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

2025/03/10 by Adolf W. Karchmer, Nathan Kaufman, Sarah Y. Park +6 · 1 voice · 6 citations
Medicine · #Antimicrobial Resistance in Staphylococcus #Cardiac pacing and defibrillation studies #Infective Endocarditis Diagnosis and Management

paper · pdf · doi:10.1093/cid/ciaf113

openalex publication_date 2025/03/10 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22

Abstract

BACKGROUND: Staphylococcus 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. METHODS: We 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. RESULTS: In 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. CONCLUSIONS: If 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.

Citations

• Update on Cardiovascular Implantable Electronic Device Infections and Their Prevention, Diagnosis, and Management: A Scientific Statement From the American Heart Association

Cited by

• Plasma Quantitative Microbial Cell-Free DNA for Staphylococcal Cardiac Implantable Electronic Device Infection—Too Soon?
• Metagenomic next-generation sequencing: new horizons in microbiology
• Diagnosing Staphylococcal Cardiac Electronic Implantable Device Endocarditis: The Potential of Quantitative Plasma Cell-Free Microbial DNA
• The Next Step: The Role of Metagenomic Next-Generation Sequencing in Microbial Detection of Culture-Negative Cardiovascular Infections
• Clinical utility of serial plasma cell-free DNA metagenomic next-generation sequencing assays
• From Suspected to Rejected: Role of Serial Plasma Microbial Cell-Free DNA Sequencing as a Diagnostic Adjunct in CIED Infections

Discussions

• Quantitative Microbial Cell-Free DNA Sequencing from Plasma: A Potential Biomarker for the Diagnosis of Staphylococcal Infection of Cardiac Implantable Electronic Devices ✅ Just Accepted #IDSky [bsky, 2 points, 0 comments]

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