Persistent microbial cell-free DNA during antibiotic therapy was found in 90.9% of patients with definite CIED-IE compared to 0% of those with possible CIED-IE (P = .001).
Observational (n=16)
Does metagenomic sequencing of microbial cell-free DNA (mcfDNA) improve diagnostic precision for staphylococcal infection of cardiac implantable electronic devices in patients with staphylococcal bacteremia?
Metagenomic sequencing of microbial cell-free DNA in plasma shows distinct patterns between definite and possible CIED-IE, suggesting its potential as a biomarker to improve diagnostic precision.
Absolute Event Rate: 90.9% vs 0%
p-value: p=.001
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.
Karchmer et al. (Mon,) conducted a observational in Staphylococcal bacteremia with cardiac implantable electronic devices (CIED-IE) (n=16). Definite CIED-IE vs. Possible CIED-IE was evaluated on Persistent mcfDNA during antibiotic therapy (p=.001). Persistent microbial cell-free DNA during antibiotic therapy was found in 90.9% of patients with definite CIED-IE compared to 0% of those with possible CIED-IE (P = .001).