The role, challenges, and innovations of rifampin in the management of periprosthetic joint infections: a narrative review

Periprosthetic joint infection (PJI) remains a severe complication due to persistent bacterial biofilms. Rifampin is traditionally valued for its unique biofilm-penetrating properties, yet its clinical role is increasingly viewed as context-dependent. While current evidence supports the efficacy of rifampin in two-stage revision arthroplasty, its application in debridement, antibiotics, and implant retention (DAIR) remains a subject of ongoing debate. Landmark randomized trials once reported superior cure rates for DAIR combined with rifampin, but contemporary large-scale retrospective data show no statistically significant difference in remission rates, often accompanied by a significantly higher incidence of adverse events. Furthermore, the timing of administration is critical; early initiation within five days post-DAIR has been linked to increased treatment failure. These challenges, alongside profound drug-drug interactions, have spurred interest in localized delivery innovations like microencapsulation and nanoparticles. While these bioengineering approaches show preclinical promise in overcoming PMMA chemical incompatibility, they remain at the proof-of-concept stage. Consequently, rifampin should be employed as a targeted adjunct rather than a universal standard, requiring careful consideration of surgical strategy, patient tolerance, and optimal timing.