Efficacy and Safety of Rifabutin in Implant-Associated Bone and Joint Infections: A Multicentre Retrospective Study

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Introduction & Aim Rifampicin is a key component in the management of implant-associated bone and joint infections (BJIs), but its use is limited by poor tolerability and numerous drug–drug interactions. Data on rifabutin in this setting remain scarce. This study aimed to evaluate the effectiveness and safety of rifabutin in implant-associated BJIs. Methods We conducted a retrospective bicentric study including all patients treated with rifabutin-based combination therapy for implant-associated BJIs between January 2019 and April 2024. Eligible patients underwent either debridement, antibiotics and implant retention (DAIR) or one-stage exchange, without prior rifampicin use. Data collected included patient characteristics, treatment outcomes at one year (remission, relapse with the same pathogen, superinfection), adverse events, and indications for rifabutin use. Results Eighty patients were included (mean age 70 ± 15 years; male-to-female ratio 0.74; mean BMI 30.9 ± 8.7 kg/m 2 ; mean Charlson comorbidity index 3.6 ± 2.1), including 54 DAIR and 26 one-stage exchanges. Staphylococci accounted for 78.7% of pathogens. At one year, 61 patients (76%) achieved remission, while 7 (8.5%) experienced relapse and 7 (8.5%) developed superinfection. Three patients (4%) died from causes unrelated to infection, and two (3%) were lost to follow-up. Adverse events occurred in 31 patients (38.7%), mainly gastrointestinal disorders (58.3%), liver enzyme abnormalities (23.3%), and neutropenia (13.3%). Treatment was completed in 64 patients (80%). Rifabutin was discontinued in 16 patients (20%), including 8 cases where only rifabutin was stopped, leading to resolution of adverse events. The main indication for rifabutin use was the presence of potential drug–drug interactions (81.3%), particularly with anticoagulants (46.1%) and antidepressants (32.3%). Only one clinically significant interaction was reported, and no thromboembolic events occurred. Conclusion Rifabutin-based regimens were associated with remission rates comparable to current standard therapies for implant-associated BJIs and a low rate of clinically significant drug–drug interactions. Rifabutin may represent a valuable alternative when rifampicin cannot be used, although hematological monitoring is warranted due to the risk of neutropenia.