PRECISION DIAGNOSIS OF BONE AND JOINT INFECTIONS: INTEGRATING PATHOLOGY, CLINICAL MICROBIOLOGY, MOLECULAR DIAGNOSTICS, AND SURGICAL MANAGEMENT A SYSTEMATIC REVIEW

Abstract

Background: Bone and joint infections (BJIs), including native osteomyelitis, septic arthritis, vertebral osteomyelitis, fracture-related infection (FRI), and periprosthetic joint infection (PJI), remain diagnostically challenging because previous antimicrobial exposure, biofilm formation, low microbial burden, sampling error, and overlap with sterile inflammatory disorders reduce the reliability of any single test. Objective: To systematically review contemporary evidence on precision diagnosis of BJIs and develop an integrated framework combining pathology, conventional clinical microbiology, molecular diagnostics, imaging, and surgical management. Methods: A PRISMA 2020-structured systematic review was developed for literature published from January 2015 through March 2026. PubMed/MEDLINE, Embase, Scopus, and Web of Science were considered. Eligible evidence addressed diagnostic or management strategies for osteomyelitis, septic arthritis, vertebral osteomyelitis, FRI, implant associated infection, or PJI. Because of heterogeneity in infection definitions, specimen types, thresholds, and molecular platforms, findings were synthesized narratively. Results: The PRISMA dataset comprised 1,773 identified records, 1,241 records screened, 262 full-text reports assessed, and 36 evidence records included in the qualitative synthesis. Across infection categories, multiple deep specimens, culture and susceptibility testing, histopathology, and selective sonication or molecular testing provided complementary evidence. Molecular approaches were most useful in culture-negative, antibiotic-exposed, fastidious, or polymicrobial infections. Surgical sampling and source control were inseparable from diagnostic accuracy. Conclusion: Precision diagnosis of BJI is best achieved through concordant evidence from clinical assessment, imaging, high-quality deep sampling, conventional microbiology, pathology, and selectively applied molecular methods. Advanced molecular tests should complement rather than replace culture, and complex discordant results should be reviewed by a multidisciplinary bone-and-joint infection team.