Inclusion Criteria:

• 1. Age 18 and 89 years
• 2. Diagnosis of diabetes mellitus, either by: 1) use of oral hypoglycemic agents or insulin at the time of enrollment; 2) a hemoglobin A1c (HgA1c) level within the past 90 days \> 6.5; or 3) a medical record diagnosis of diabetes mellitus by a clinician on two or more occasions in the previous 10 years
• 3. Definite or probable osteomyelitis in the diabetic foot, as defined by the International Working Group on the Diabetic Foot (Table 1). Criteria must be present at some point within 90 days prior to enrollment.
• 4. All planned debridement has been completed prior to randomization.
• 5. A course of backbone antimicrobial therapy has been selected.

Exclusion Criteria:

• 1. Patient unable to receive enteral medication.
• 2. Patient is allergic to or intolerant of rifampin.
• 3. Patient is taking a drug that has interactions with rifampin that would require either stoppage, substitution or an empiric dose modification that may place the patient at medical risk.
• 4. Within 30 days of enrollment, patient is taking immunosuppressive medications to prevent rejection of an organ transplant or is receiving chemotherapy for cancer or molecularly targeted therapies for cancer.
• 5. Patient is receiving antiretroviral therapy for HIV or antiviral medication for Hepatitis C.
• 6. Patient is participating in another interventional clinical trial for which a waiver of dual enrollment with CSP#2001 has not been obtained.
• 7. Patient has an ALT \> 3 times the upper limit of normal for the site laboratory, or total bilirubin \> 2.5 times the upper limit of normal for the site laboratory\*,\*\*\*; INR \> 1.5, OR patient has Child-Pugh Class C Cirrhosis.
• 8. Patient has a baseline white blood cell count (WBC) \<2000 cells/mm3\*\*\* OR absolute neutrophil count (ANC) \<1000 cells/mm3\*\*\* OR platelet count \<50,000 cells/mm3\*\*,\*\*\* OR hemoglobin \<8.0 g/dL.\*\*,\*\*\*.
• 9. Women of child-bearing potential (those with menses within the last year) with a positive serum pregnancy test.
• 10. Patient is believed unlikely to be able to complete the trial due to medical conditions.
• 11. Patient is believed unlikely to complete the trial due to neurologic and psycho-behavioral disorders such as active substance abuse or dependence, disabling dementias or psychoses.
• 12. Patient refuses or is clinically unable to undergo the recommended level of debridement.
• 13. Indwelling hardware present in the foot, at the site of the index osteomyelitis.
• 14. Treatment with antibacterial agents for infection at another site, where the duration of treatment is anticipated to be greater than 14 days.
• 15. Patient is receiving therapy for COVID-19 that interacts with rifampin.
• * Patients with total bilirubin \> 2 times the ULN who have Gilbert's Disease or any other inherited disease affecting bilirubin metabolism without meeting other exclusionary criteria, may be considered for inclusion in the study.
• * Patients with platelet count \<50,000 cells/mm3 due only to hypersplenism and meeting no other exclusionary criteria may be considered for inclusion in the study.
• * If multiple laboratory values are available, the most recent value will be applied for eligibility.