Implantable cardioverter-defibrillator infection by <i>Streptococcus intermedius</i> identified by next-generation sequencing

ntroduction: 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.