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Case Report
1 Medical Director, Center for Infectious Diseases, UNC Health Pardee, Hendersonville, NC, United States
2 Clinical Pharmacist Practitioner, Center for Infectious Diseases, UNC Health Pardee, Hendersonville, NC, United States
3 Department of Cardiology, UNC Health Pardee, Hendersonville, NC, United States
4 MS, MLS (ASCP)CM, CIC, FAPIC, Independent Contributor, Hendersonville, NC, United States
5 Department of Biology, Elon University, Elon, NC, United States
6 CIC, Infection Preventionist, Infection Prevention and Control, UNC Health Pardee, Hendersonville, NC, United States
Address correspondence to:
Chris Parsons
Medical Director, Center for Infectious Diseases, UNC Health Pardee, 705 6th Avenue West, Hendersonville, NC 28806,
USA
Message to Corresponding Author
Article ID: 100016Z16CP2025
Introduction: Culture-negative endocarditis refers to inflammation of endocardial structures with no etiology identified using standard diagnostic methodology. This entity continues to pose a challenge for clinicians. Definitive approaches for identifying infectious etiologies of culture-negative endocarditis are not feasible in clinical practice, including cultures or molecular testing performed directly on valvular tissue. Serologic assays for key pathogens and standard polymerase chain reaction (PCR) methodology applied to peripheral blood have increased diagnostic acumen in these cases. Yet, even with application of these methods, etiologies often remains elusive. Next-generation sequencing (NGS) and categorization of DNA using a large library of DNA sequences can be performed following extraction of microbial cell-free DNA (mcfDNA) from peripheral blood. Through advances in this technology and clinical application, these methods are now available through commercial laboratories utilizing high-throughput systems, and NGS of mcfDNA now offers an important advance in the diagnostic evaluation for culture-negative endocarditis.
Case Report: A 49-year-old male with an indwelling implantable cardioverter-defibrillator (ICD) developed progressive weight loss, chills, diaphoresis, and hypotension. Echocardiography revealed an ICD lead vegetation. Standard blood cultures revealed no growth, but NGS applied to mcfDNA isolated from peripheral blood identified Streptococcus intermedius as the etiologic agent. The patient made a full recovery with antibiotics targeting this organism.
Conclusion: Next-generation sequencing led to successful targeted antibiotic therapy, avoidance of unnecessary surgical procedures, and a full recovery for our patient with culture-negative endocarditis involving his ICD and offers an important diagnostic advance for patients with indwelling devices.
Keywords: Bacteremia, Culture-negative, Endocarditis, Next-generation sequencing
Chris Parsons - Substantial contributions to conception and design, Acquisition of data, Analysis of data, Interpretation of data, Drafting the article, Final approval of the version to be published
Stephen Vickery - Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Aaron Timins - Acquisition of data, Analysis of data, Interpretation of data, Drafting the article, Final approval of the version to be published
Ivan Gowe - Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Adam Parsons - Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Ashley Reyes - Acquisition of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Guaranter of SubmissionThe corresponding author is the guarantor of submission.
Source of SupportNone
Consent StatementWritten informed consent was obtained from the patient for publication of this article.
Data AvailabilityAll relevant data are within the paper and its Supporting Information files.
Conflict of InterestAuthors declare no conflict of interest.
Copyright© 2025 Chris Parsons et al. This article is distributed under the terms of Creative Commons Attribution License which permits unrestricted use, distribution and reproduction in any medium provided the original author(s) and original publisher are properly credited. Please see the copyright policy on the journal website for more information.