Hospitalizations for severe infections associated with opioid use disorder (OUD), such as infective endocarditis (IE), have doubled in the US over the past decade and are frequently prolonged and resource-intensive. Once medically stabilized, persons with IE but without drug use typically enroll in outpatient parenteral antibiotic therapy (OPAT), while persons with IE and OUD are kept in the hospital for the duration of therapy (often 6 weeks or more) largely due to concerns of ongoing drug use. Unfortunately, hospitalization for IE with OUD infrequently includes evidence-based medication-assisted treatment (MAT) with buprenorphine or methadone to address the OUD, despite the strong evidence that MAT decreases illicit drug use and mortality. Enrolling hospitalized persons with IE due to OUD into comprehensive MAT (i.e., buprenorphine + counseling) while inpatient, and providing an intensive transitional outpatient care program supporting MAT, may support provision of outpatient IV antibiotic therapy and be cost effective. The primary aim of this pilot randomized clinical trial is to evaluate the equivalence of current practice plus buprenorphine (keeping patients with IE due to opioid use disorder in the hospital for the full duration of antibiotic treatment) compared to OPAT plus buprenorphine (discharge with outpatient treatment once medically stable).

Inclusion Criteria:

• meeting OUD by DSM-V criteria
• have IE by Duke's criteria
• candidates for outpatient treatment with buprenorphine
• accepting of buprenorphine treatment
• anticipated to be discharged home after medically stabilized
• requiring ≥ 2 weeks of IV antibiotic therapy
• having ≥ 1 week of IV antibiotic therapy remaining at the time of medical readiness for discharge (as defined by the primary clinical team),
• and providing informed consent.

Exclusion Criteria:

• presence of stroke or central nervous system involvement
• clinically active embolic sequelae (e.g. pulmonary sepsis, mycotic aneurysms, splenic abscesses)
• TV treated surgically or endovascularly (AngioVac)
• presence of osteomyelitis
• fungal IE
• patients who require inpatient physical rehabilitation determined by physical or occupational therapy assessment
• current pregnancy
• current severe methamphetamine, cocaine, alcohol or benzodiazepine use disorders by DSM-V criteria
• currently enrolled in ongoing MAT for OUD
• hypersensitivity or allergy to buprenorphine
• chronic pain requiring opioids
• class III or IV heart failure
• cirrhosis
• end stage renal disease
• other significant screening laboratory/medical/psychiatric/psychosocial condition that may prevent the volunteer from safely participating in the study in the opinion of the investigator (e.g. currently suicidal)
• pending legal action that could interfere with study participation
• living more than a 45-minute drive from UK given the intense outpatient component to the intervention.