France Laurent, Jean Cyr Yombi
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.
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.