Current Concepts in Periprosthetic Joint Infection: Modern Biomarkers, Microbiome Insights, Molecular Diagnostics, and Emerging Prevention Strategies.

Aim: Periprosthetic joint infection (PJI) remains one of the leading causes of revision arthroplasty and is associated with substantial morbidity, mortality, and healthcare costs. Diagnosis remains challenging because of heterogeneous clinical presentations, the limited sensitivity of conventional inflammatory markers in chronic and low-grade infections, culture-negative cases, and biofilm-mediated pathogen persistence. This narrative review summarizes recent advances in the diagnosis and prevention of PJI, with a particular focus on synovial and serum biomarkers, microbiome-related susceptibility, molecular diagnostics, artificial intelligence, and emerging anti-biofilm and implant-surface technologies. Synovial biomarkers, including alpha-defensin, leukocyte esterase, calprotectin, and D-lactate, have demonstrated improved diagnostic performance, particularly in equivocal and culture-negative cases. However, none has sufficient evidence to replace established diagnostic criteria, and current data support their use as adjunctive tools in selected clinical scenarios rather than as standalone tests. Serum biomarkers beyond erythrocyte sedimentation rate and C-reactive protein, such as fibrinogen and protein fraction alterations, may provide additional diagnostic value but require further validation and standardized diagnostic thresholds. Molecular approaches, particularly metagenomic next-generation sequencing, improve pathogen detection in complex infections but remain limited by cost, protocol variability, and challenges in distinguishing clinically relevant pathogens from contaminants. Preventive strategies targeting bacterial adhesion and biofilm formation through local antibiotic delivery, surface modification, and nanotechnology-enabled implants are promising, although long-term efficacy, safety, and cost-effectiveness remain to be established. Overall, PJI management is evolving toward integrated, multimodal diagnostic strategies and biologically informed prevention. Current evidence supports the selective clinical use of synovial biomarker testing as an adjunctive tool within established diagnostic criteria, while continued research is needed before widespread routine implementation can be recommended. Statement of Clinical Significance: Modern synovial biomarkers provide valuable adjunctive information that may improve diagnostic confidence in challenging periprosthetic joint infection cases when incorporated into a multidisciplinary diagnostic approach involving clinical assessment, laboratory evaluation, microbiological analysis, and established consensus criteria. Emerging preventive strategies targeting biofilm formation and host-microbe interactions represent promising approaches, although their ability to reduce revision rates and improve patient outcomes requires further clinical validation.