1298. High Prescription Rate of Medications with Significant Rifampin Drug Interactions in Patients with Diabetic Foot Osteomyelitis: Should Rifabutin be Included in Clinical Trials for Adjunctive Therapy?

Abstract

Abstract Background Diabetic foot osteomyelitis (DFO) is a leading cause of amputations. Rifamycins can penetrate osteoblasts and disrupt biofilm, making them ideal adjunctive antibiotics for DFO. A recent retrospective DFO study found that rifampin adjuvant therapy was associated with significantly higher amputation-free survival rate and randomized clinical trials to establish whether adjunctive rifampin therapy improves DFO outcomes are ongoing. Rifamycin use is complicated by drug-drug interactions (DDIs), primarily due to cytochrome P450 induction. However, rifabutin is a less potent and broad cytochrome P450 inducer versus rifampin. We evaluated DDI predicted rates of rifampin and rifabutin in a DFO cohort. Methods We conducted a retrospective cohort study of all patients hospitalized with DFO between 2017 and 2019 at Grady Memorial Hospital (Atlanta, GA). We queried discharge billing records using ICD-10 codes for DFO and performed a chart review to confirm the diagnosis. We used the Lexicomp DDI tool to determine the number of potential DDIs between all medications prescribed upon discharge and rifampin or rifabutin. Results There were a total of 530 hospital admissions among 330 unique patients for DFO of which 70% were male and 80% were Black. The mean hemoglobin A1c was 9.4%. Chronic kidney disease was present in 69% of patients. Among 239 DFO cases with a culture, S. aureus was identified in 79 (33%). Eighty-nine (27%) patients were prescribed medications with a class X (“avoid combination”) rifampin interaction versus 4 (1%) patients who were prescribed drugs with a rifabutin class X interaction. Two-hundred-and-forty (73%) patients had prescriptions for medications with a class D (“avoid combination”) rifampin interaction versus 15 (5%) with a class D rifabutin interaction. The most common medications with class X rifampin DDIs were proton pump inhibitors (20%) and directly acting oral anticoagulants (5.7%), while those for class D rifampin DDIs were atorvastatin (35%) and clopidogrel (12%). Conclusion A high percentage of patients with DFO were prescribed medications with significant rifampin DDIs compared with rifabutin, supporting the need to investigate rifabutin for adjunctive DFO therapy. Disclosures All Authors: No reported disclosures