Tropheryma whipplei native valve endocarditis diagnosed by sequencing of microbial cell-free DNA in plasma

October 1, 2025
Clinical Microbiology
Peter M Rabinowitz, Ritika Walia, Paul Pottinger, Joshua A Lieberman
Pathogen:Tropheryma whipplei
Infection Type:Native valve endocarditis
Pathogen Type:Bacteria

Summary

A 58-year-old male presented with a two-month history of fever, weight loss, and fatigue, ultimately diagnosed with native valve endocarditis. Initial blood cultures were negative, and echocardiography revealed mitral valve vegetations. Despite empirical antibiotic therapy, his condition worsened. Diagnosis was challenging until plasma microbial cell-free DNA sequencing identified Tropheryma whipplei. This advanced diagnostic method enabled targeted treatment with doxycycline and hydroxychloroquine, leading to clinical improvement and discharge. This case highlights the critical role of mcfDNA sequencing in diagnosing culture-negative endocarditis caused by fastidious organisms like T. whipplei, preventing diagnostic delays and improving patient outcomes.

Key note: Plasma microbial cell-free DNA sequencing is a valuable tool for diagnosing culture-negative endocarditis, especially for difficult-to-cultivate pathogens.

DOI: 10.1128/asmcr.00070-25