395. Safety and Tolerability of Rifampin in Staphylococcal Orthopedic Infections

BACKGROUND: Rifampin is part of optimal combination antimicrobial therapy for staphylococcal foreign-body infections, including periprosthetic joint infections (PJI) in cases of retained prostheses. However, rifampin can have important drug interactions, can cause hepatotoxicity and other organ toxicity, and can induce treatment-limiting side effects. Although rifampin safety and tolerability is well-described in tuberculosis patients, its use in orthopedic infections is poorly described. We therefore analyzed the safety and tolerability of rifampin in patients with staphylococcal hip and knee PJIs treated with implant retention. METHODS: A retrospective institutional PJI database was queried to identify all staphylococcal PJI cases treated with implant retention, from 2008 to 2016. Patient demographics, comorbidities, and antibiotic treatment course were collected. The Chi-square or Fisher’s exact test was used for comparisons between rifampin-tolerant (RT) and -intolerant (RI) subgroups. RESULTS: 80 patients were included, of which 75 (94%) began rifampin. Of the 75 who received rifampin, 23% (17/75) were RI. The median duration of rifampin for RT was 3.0 months (range 1–60) and 0.75 months for RI (range 0.1–3). Reasons for RI included allergies (N = 6), GI toxicity (N = 5), increased liver function tests (N = 2), leukopenia (N = 2), acute kidney injury (N = 1), exacerbated epilepsy (possibly due to low phenytoin; N = 1), and vasculitis (N = 1). Patient age, sex, and Charlson comorbidity index did not predict rifampin intolerance. In 5/80 (6%) patients who never received rifampin, reasons included liver disease, drug interactions, and rifampin resistance. Overall, 27% (22/80) could not be adequately treated with rifampin. CONCLUSION: In this study cohort of PJI patients, contraindications to rifampin initiation were infrequent, but discontinuation due to intolerance, allergy, or toxicity occurred in nearly a quarter of patients. Drug-drug interactions can preclude its use, or may cause important medication switches in critical areas such as anticoagulation, epilepsy treatment, and HIV care. Research into the anti-staphylococcal efficacy and safety of alternative rifamycins (such as rifabutin and rifapentine) in patients with staphylococcal hardware infections is warranted. DISCLOSURES: All authors: No reported disclosures.