Question: What is the most clinically beneficial and cost-effective antibiotic treatment strategy for injection drug use–associated infective endocarditis (IDU-IE)?

Findings: In this decision analytical modeling study simulating 4 treatment strategies among 5 million individuals with IDU-IE in the US, a validated microsimulation model suggested that outpatient parenteral antimicrobial therapy was the most cost-effective strategy for the treatment of IDU-IE. A partial oral antibiotic treatment strategy was associated with the highest treatment completion rate and was most cost-effective when methicillin-resistant Staphylococcus aureus was not a causative pathogen.

Meaning: This study found that outpatient parenteral antimicrobial therapy and partial oral antibiotic therapy regimens were likely to be as clinically beneficial as and less costly than 6 weeks of inpatient intravenous antibiotic therapy for the treatment of IDU-IE.