Key result
Persistent plasma microbial cell-free DNA distinguishes definite from possible CIED infective endocarditis during treatment.
Why the study?
Diagnosis of CIED infective endocarditis in staphylococcal bacteremia is syndromic with frequent diagnostic uncertainty, leading to guideline-noncompliant treatment and heterogeneous outcomes.
Does serial measurement of plasma microbial cell-free DNA differentiate definite from possible cardiac implantable electronic device infective endocarditis in patients with staphylococcal bacteremia?
Cohort (n=16)
No
Does serial measurement of plasma microbial cell-free DNA differentiate definite from possible cardiac implantable electronic device infective endocarditis in patients with staphylococcal bacteremia?
Quantitative microbial cell-free DNA sequencing in plasma demonstrates potential as a novel biomarker to clarify diagnosis and guide management in patients with CIEDs and staphylococcal bacteremia.
Answers are grounded in this paper and cite their sources.
May aid differentiation of definite from possible CIED-IE in staphylococcal bacteremia; hypothesis-generating and requires prospective validation before guiding care.
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.
No takes yet. Share an insight, caveat, or question.
Karchmer et al. (2025) conducted a cohort in Staphylococcal bacteremia in patients with cardiac implantable electronic devices (CIEDs) (n=16). Serial metagenomic sequencing of microbial cell-free DNA (mcfDNA) vs. Patients with possible CIED-IE (compared to definite CIED-IE) was evaluated on Difference in kinetic patterns of staphylococcal mcfDNA in plasma during antibiotic therapy and around device extraction (p=0.001). Plasma microbial cell-free DNA persisted during antibiotic therapy and increased early after extraction in definite CIED-IE cases, but rapidly became undetectable in possible CIED-IE cases (P = .001).
Synapse has enriched 10 related papers. Consider them for comparative context: