● Men and Women age ≥ 18 and ≤ 89 years
● Diabetes Mellitus
○ Defined either by: 1) use of oral hypoglycemic agents or insulin at the time of enrollment; or 2) a hemoglobin A1c (HgA1c) level within the past 90 days >6.5
● Definite or probable osteomyelitis of the foot (DFO)
○ Defined by the International Working Group on the Diabetic Foot (Table 1)
● All planned debridement has been completed prior to randomization
● A definitive course of backbone antibiotic treatment has been selected
● Patient is unable to receive enteral medication
● Patient is allergic to or intolerant of rifampin
● 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
● Within 30 days of enrollment, patient is taking immunosuppressive medications to prevent rejection of an organ transplant or is receiving chemotherapy or molecularly targeted therapies for cancer
● Patient is receiving antiretroviral therapy for HIV or antiviral medication for Hepatitis B or C
● Enrollment in another trial of a therapeutic agent with a documented or suspected interaction with rifampin
● 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; patient has Child-Pugh Class C Cirrhosis.
● Patient has a baseline white blood cell count (WBC) <2000 cells/mm3 OR platelet count <50,000 cells/mm3 OR hemoglobin <8.0 g/dL.
● Women of child-bearing potential (those with menses within the last year) with a positive serum pregnancy test.
● Patient is believed unlikely to be able to complete the trial due to medical conditions such as metastatic cancer or end-stage organ failure
● 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
● Patient refuses or is clinically unable to undergo the recommended level of debridement
● Patient’s prescribed backbone antibiotic therapy does not meet standard of care for either empirical treatment or culture-directed therapy
● Indwelling hardware present in the foot, at the site of the index osteomyelitis
● Treatment with antibacterial agents for infection at another site, where the duration of treatment is anticipated to be greater than 14 days