Integrating molecular and conventional diagnostics in native vertebral osteomyelitis: a narrative review

Native vertebral osteomyelitis (NVO) remains a diagnostic challenge due to its non-specific presentation and the limited sensitivity of culture-based methods. Blood cultures and image-guided biopsies are considered the diagnostic standards, but their yield is often low, especially in patients who have received prior antibiotics or are infected with fastidious microorganisms. Recent molecular techniques, including polymerase chain reaction (PCR) and next-generation sequencing (NGS), have improved pathogen detection and enabled more targeted antimicrobial therapy. In this narrative review, we summarize the diagnostic methods used in NVO, including conventional microbiological and molecular approaches, and present their strengths and limitations based on previous studies. We particularly focus on situations where molecular diagnostic techniques, such as 16S rRNA PCR, NGS, and microbial cell-free DNA testing, outperform traditional culture-based methods in sensitivity, while their specificity may be comparatively lower. Combining these molecular tools with standard diagnostic procedures may improve pathogen detection, guide targeted treatment, and enhance diagnostic accuracy in culture-negative or antibiotic-pretreated cases. Understanding the advantages and limitations of each diagnostic method can help clinicians to choose the most appropriate testing strategy, reduce diagnostic delays, and improve patient management in suspected NVO.