Rifampicin in Osteoarticular Infections: A Comprehensive Review of Current Evidence

Background. Osteoarticular infections (OAI)—including prosthetic joint infections (PJI), fracture-related infections (FRI), and osteomyelitis—are challenging to cure because bacterial biofilm on implant surfaces confers up to 1000-fold antibiotic tolerance, driving chronicity and relapse. Rifampicin, through its bactericidal activity against quiescent, biofilm-embedded bacteria and excellent oral bioavailability, occupies a pivotal role in managing Gram-positive OAI. Methods. This comprehensive narrative review synthesises mechanistic, preclinical, and clinical evidence on rifampicin across the three major osteoarticular infection types and by causative pathogen. PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library were searched (January 1990–June 2026); of several hundred candidate records identified, the 101 most relevant were selected for narrative synthesis. Results. The strongest evidence supports rifampicin in staphylococcal PJI managed with debridement, antibiotics, and implant retention (DAIR), with fluoroquinolones as optimal companions; monotherapy invariably selects resistant mutants. This benefit is expected to extend beyond PJI to other osteoarticular infections managed with hardware retention—fracture-related infection and implant-associated osteomyelitis—given the shared biofilm target on retained metalwork. Benefit is attenuated in implant-exchange procedures, and evidence for streptococci, Cutibacterium acnes, and enterococci remains insufficient for firm recommendations. Conclusions. Rifampicin remains a valuable, difficult-to-replace agent in staphylococcal PJI treated with DAIR, provided it is introduced after surgical source control and combined with a fluoroquinolone. Observational data suggest possible benefit from introduction beyond 5 days post-debridement and courses of at least 14 days, but each threshold rests on a single study and requires confirmation. High-quality randomised trials targeting others OAI with implant retention, non-staphylococcal pathogens, optimal dosing, and treatment duration are needed.