Revealing Hidden Pathogens: Culture-Negative Vertebral Osteomyelitis Diagnosed via Plasma DNA Sequencing

Abstract Vertebral osteomyelitis is a rare and often delayed diagnosis, particularly when cultures are negative and symptoms are nonspecific. Hematogenous spread from the genitourinary tract is an underrecognized mechanism, especially following urologic procedures. Batson's plexus—a valveless venous network—may facilitate retrograde microbial seeding of the spine even in the absence of bacteremia. We present a 66-year-old man with progressive lower back pain and weight loss 7 weeks after ureteral stent placement. Magnetic resonance imaging revealed L4–L5 osteomyelitis with epidural phlegmon and psoas myositis. Despite negative cultures and biopsy, plasma microbial cell-free DNA sequencing identified Candida albicans and Aerococcus urinae . He was treated with ceftriaxone and fluconazole with clinical improvement. This appears to be the first reported case of vertebral osteomyelitis caused by both organisms. It illustrates the utility of next-generation sequencing in culture-negative spinal infections and reinforces the importance of considering urologic sources and atypical pathogens in the appropriate clinical context.