More Habit than Hard Evidence? Rifampin in Orthopedic Implant Infections: A Practical Guide for Clinicians

Orthopedic implant infections—including prosthetic joint infections (PJI), fracture-related infections (FRI), and spinal implant infections (SII)—represent a spectrum of biofilm-associated infections that are associated with substantial morbidity, prolonged antimicrobial therapy, and frequent need for surgical intervention. Rifampin is often incorporated into antimicrobial treatment regimens for orthopedic implant infections due to its potent biofilm-penetrating properties and has been most studied in the treatment of staphylococcal PJIs, though the majority of data is observational. Its use is frequently complicated by adverse effects and significant drug–drug interactions, and the role of rifampin beyond staphylococcal PJIs managed with implant retention or one-stage exchange remains controversial. In this review, we critically evaluate the evidence for use of rifampin in PJI, with additional consideration of its role in FRIs, SIIs, and PJIs caused by staphylococcal and other Gram-positive organisms. Using illustrative cases, we provide a practical framework for navigating common clinical scenarios and challenges involving the use of rifampin in orthopedic implant infections.