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Revealing Hidden Pathogens: Culture-Negative Vertebral Osteomyelitis Diagnosed via Plasma DNA Sequencing
Trishtha Agarwal, MD1; David Kornblum, MD2; Kartikeya Cherabuddi, MD2; Jacqueline Sherbuk, MD2 1Department of Internal Medicine, Kasturba Medical College, Manipal, Karnataka , India 2Department of Infectious Disease, University of South Florida, Tampa, FL, USA
Background - Vertebral osteomyelitis (VO) is a rare but potentially debilitating infection, commonly resulting from hematogenous spread. While typical pathogens include Staphylococcus aureus and gram-negative bacilli, rare organisms such as Candida albicans and Aerococcus urinae have emerged in specific patient populations, particularly those with recent urologic procedures. The valveless vertebral venous plexus (Batson’s plexus) facilitates retrograde spread from the pelvic organs to the spine, even in the absence of systemic bacteremia. Diagnosis is often delayed due to nonspecific symptoms and low culture yield.
Case Presentation - A 66-year-old male with a history of ureteral stent placement presented with seven weeks of progressive lower back pain and unintentional weight loss. MRI revealed L4-L5 vertebral osteomyelitis with epidural phlegmon and psoas myositis. Blood cultures and CT-guided biopsy were negative. Plasma microbial cell-free DNA sequencing (Karius test) identified Candida albicans and Aerococcus urinae. Given the patient’s recent genitourinary instrumentation, these organisms were considered causative. He was treated with intravenous ceftriaxone and oral fluconazole and discharged with a peripherally inserted central catheter (PICC) line for outpatient therapy.
Discussion- This is the first documented case of vertebral osteomyelitis due to concurrent C. albicans and A. urinae, likely seeded hematogenously from the urinary tract via Batson’s plexus. It underscores the value of cell-free DNA sequencing in diagnosing culture-negative spinal infections and supports its early use in patients with compatible clinical and radiologic features when conventional testing is nondiagnostic.