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The following is a summary of “Quantitative Microbial Cell-Free DNA Sequencing from Plasma: A Potential Biomarker for the Diagnosis of Staphylococcal Infection of Cardiac Implantable Electronic Devices,” published in the March 2025 issue of Clinical Infectious Diseases by Karchmer et al. 

Diagnostic challenges in differentiating Staphylococcus aureus bacteremia with possible cardiac implantable electronic device infective endocarditis (CIED-IE) from definite CIED-IE lead to inconsistent treatment and outcomes.  

Researchers conducted a retrospective study to assess whether metagenomic sequencing of microbial cell-free DNA (mcfDNA) in serial plasma specimens improved diagnostic precision in individuals with CIED-IE.  

They analyzed 16 individuals with staphylococcal bacteremia classified as definite or possible CIED-IE and recommended device removal if a positive blood culture was detected within 7 days without concurrent deep infection. Plasma samples collected at consent, before extraction, and up to 96 hours post-extraction underwent metagenomic sequencing and quantification of staphylococcal mcfDNA.  

The results showed that in 10 of 11 individuals with definite CIED-IE, mcfDNA persisted despite antibiotic therapy for a median of 11 days (IQR 7.5 days [7.5,15]). In these cases, mcfDNA levels in plasma rose significantly after lead extraction before declining rapidly. In 5 individuals with possible CIED-IE, mcfDNA was undetectable after 6 days (IQR 2 days [5.5,7.5]) of antibiotic therapy and remained absent following device extraction. These distinct mcfDNA patterns (P =0.001) indicated 2 separate groups: 1 with definite CIED-IE and 1 without lead infection.  

Investigators concluded that circulating mcfDNA patterns, if validated, could enhance the accuracy of S. aureus CIED-IE diagnosis and guide treatment planning, especially around CIED extraction. 

Source: academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf113/8069245