How Often Is Rifampin Therapy Initiated and Completed in Patients With Periprosthetic Joint Infections?
Authors: Kugelman David N. , Leal Justin , Shah Sharrieff , Wrenn Rebekah , Mackowiak Amy , Ryan Sean P. , Jiranek William A. , Seyler Thorsten M. , Seidelman Jessica 
Published: January 2025

Background
Rifampin therapy is indicated for the treatment of staphylococcal periprosthetic joint infection (PJI) in patients who have undergone debridement, antibiotics, and implant retention (DAIR) or one-stage revision as per the Infectious Diseases Society of America (IDSA) guideline. Given the well-established effectiveness of rifampin as adjunctive therapy in staphylococcal PJI, it is crucial to evaluate its utilization in practice and identify factors that contribute to its underuse or incomplete administration, as these deviations may undermine treatment efficacy and patient outcomes.

Questions/purposes
Among patients who met clear indications for rifampin use having undergone DAIR or one-stage revision for staphylococcal PJI, (1) what proportion of patients did not receive it? (2) What proportion of patients started it but did not complete the planned course? (3) Where documented in the medical record, what were the common reasons for not using it or prematurely discontinuing it, and in what percentage of the patients’ charts was no reason given? (4) What proportion of patients were taking a medication that put them at risk for a drug-drug interaction (DDI)?

Methods
Using an institutional database, patients who underwent DAIR or revision arthroplasty for PJI from January 2013 to April 2023 were identified (n = 935). We defined clear indications for rifampin use as a patient diagnosed with staphylococcal PJI treated via DAIR or one-stage revision, as set forth by the clinical practice guidelines of the IDSA. Based on those indications, we surveyed patients’ electronic medical records (EMRs) and calculated the proportion of patients who did not receive the drug in situations where it would have seemed appropriate that they receive it. We then determined the planned length of antibiotic management and calculated the proportion of patients whose planned courses of rifampin were not completed based on what was documented in each patient’s chart. Next, we performed a review of the EMR and recorded qualitatively the reasons why patients either did not receive rifampin or why the planned course was not completed, as well as the percentage of patients whose medical records did not indicate why the drug was not used or was discontinued before the planned course had been administered. Last, we retrospectively reviewed the medications that the patients were taking at the time of indicated adjunctive rifampin initiation and evaluated whether there were DDIs and the potential severity of those interactions.

Results
A total of 9% (87 of 935) of patients who underwent DAIR or revision arthroplasty for PJI met IDSA criteria, suggesting that rifampin use would have been appropriate. Of those meeting IDSA criteria, 49% (43 of 87) started rifampin. Of those who started on rifampin for staphylococcal PJI, 19% (8 of 43) discontinued it before the planned 6-week course was complete as documented in the EMR. Among the patients who did not receive rifampin when it appeared that they ought to have based on IDSA criteria, no reason for this decision was documented in 70% (31 of 44); among those for whom a reason was documented, it was DDI in 8 of 13, concern for hepatotoxicity in 1 of 13, history of a side effect in 1 of 13, and other reasons in 3 of 13. Among the patients whose courses were terminated before the planned course was completed, it was a gastrointestinal issue in 5 of 8, acute kidney injury in 1 of 8, or other reasons in 2 of 8.

Conclusion
Only about one-half of patients who met IDSA criteria for adjunctive rifampin therapy for staphylococcal PJI after DAIR or one-stage revision at a large tertiary referral academic center were started on treatment. For most patients who did not receive rifampin, there is no documentation for why not. Given the evidence of superior outcomes for patients treated with adjunctive rifampin, it is imperative that all patients meeting criteria be started on the medication unless there is a clear contraindication, which should be documented. Future studies should further evaluate the clinical benefit of rifampin when treating staphylococcal PJI and which DDIs would be considered true contraindications of treatment. This could be achieved with a prospective study that evaluates successful long-term infection-free survival after treatment with adjunctive rifampin while accounting for and stratifying the potential clinical risk of these DDIs.

Level of Evidence
Level IV, therapeutic study.